Good morning. Welcome to Sage Therapeutics' fourth quarter and full year 2022 financial results conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Sage's website at sagerx.com. Recording, reproduction, or transmission of this call without the express written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Helen Rubinstein, Director of Investor Relations at Sage. Good morning, thank you for joining Sage Therapeutics' Q4 and full year 2022 financial results conference call. Before we begin, I encourage everyone to go to the Investors and Media section of our website at sagerx.com, where you can find the press release related to today's call, as well as the slides that we will be reviewing today. I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. Please review the risk factors discussed in today's press release and in our SEC filings for additional details. We will begin the call with prepared remarks by Barry Greene, our Chief Executive Officer, who will provide an overview of our progress during the Q4 and full year 2022. We will also be joined by Jim Doherty, our Chief Development Officer, who will review recent progress in development activities across our programs. Our Chief Business Officer, Chris Benecchi, will provide an update on our launch preparations for Zuranolone in MDD and PPD, if approved. We will then be joined by Kimi Iguchi, our Chief Financial Officer, who will review the financial results from the Q4 and full year 2022. Laura Gault, our Chief Medical Officer, will be available for questions during the Q&A portion of the call. With that, I'll now turn the call over to Barry. Thanks, Helen. Thank you everyone for joining us this morning. At Sage, we're advancing potential treatments for brain health by challenging convention and prioritizing what matters most to patients. Today, our work matters more than ever. We've reached a public health crisis tipping point. Brain health disorders are one of the leading causes of disability and threaten to impact future generations. We see profound implications firsthand as friends, loved ones, and neighbors continue to struggle. Yet, over the last half-century, there have been insufficient advances in the treatment of mood, cognition, and other disorders of the brain. People deserve better, and we're determined to change the trajectory of this crisis. This is an incredibly exciting time at Sage. We're progressing a promising and targeted brain health pipeline with the potential to impact millions of people globally. The pipeline is a result of our innovative approach to drug discovery and development, which starts with our novel work on the GABA and NMDA receptor systems. These pathways are important regulators of brain function and the key to unlocking potential breakthroughs that may improve brain health. Importantly, we believe our team and our strong financial foundation puts us in a position to further our pipeline ambitions with a goal of being able to launch new drugs or indications for years to come. The time is now to unleash the potential of our science in making meaningful impact on the lives of millions. Moving to the next slide. We're making progress across our pipeline, as demonstrated by the latest regulatory milestone for Zuranolone, which we're developing in collaboration with Biogen. As we recently announced, we're encouraged by the FDA acceptance of our NDA filing for Zuranolone with priority review in major depressive disorder and postpartum depression, with the PDUFA action date of August 5th of this year. If approved, we expect a potential launch near the end of 2023, assuming no extensions of the FDA review period. With that timing in mind, we remain laser-focused on preparing for the potential commercialization of Zuranolone, which Chris will walk through in more detail. Our commitment to be as innovative in helping to enable access to treatment as we're developing our medicines will be a key aspect of our overall commercialization strategy. To achieve that, we're collaborating across the ecosystem with payers, healthcare providers, patient advocates, and policymakers with a goal of providing a model for care that works in the best interest of patients with MDD and PPD. We look forward to providing updates as appropriate. I would like to note, since we now are in an FDA review period, we will not be making comments on the potential label, FDA interactions, or related topics. In addition to Zuranolone, we have a robust pipeline of investigational programs that have potential to help patients at all stages of their lifespan, with 9 clinical studies ongoing. These include SAGE-718, our first-in-class NMDA-PAM, which we're currently advancing in 4 placebo-controlled studies and an extension study across Huntington's disease, Parkinson's disease, and Alzheimer's disease. We're also making important progress in our neurology franchise led by SAGE-324, which is being evaluated as a potential treatment for people suffering from essential tremor and other neurological disorders. I'd also like to highlight some of our earlier stage programs, including SAGE-319 and SAGE-689. These are great examples of our product engine that we believe will continue to deliver robust product candidates and have the potential for long-term value creation. To close, I am confident 2023 will be a pivotal year for Sage. Particularly as we look forward to the potential approval of Zuranolone and the advancement of our brain health pipeline. With that, I'll turn the call over to Jim for a more detailed discussion of our recent portfolio progress and current clinical expectations. Jim? Thanks, Barry, and good morning, everyone. We've made important progress across our development pipeline throughout 2022, and I am pleased to detail our recent advancements. Starting with depression, we're excited about the recent FDA acceptance of our NDA filing for Zuranolone in MDD and PPD with priority review, as Barry mentioned earlier. Our NDA package is supported by seven positive trials across the LANDSCAPE and NEST clinical development program, which encompasses data from more than 3,500 patients. Importantly, we've seen a consistent clinical profile to date across the development program in MDD and PPD, including a rapid and sustained reduction in depressive symptoms as early as 2 or 3 days, a generally well-tolerated safety profile, improvements in quality of life and overall health across domains of feeling, functioning, and well-being, which I'll talk more about shortly, and a short treatment course with the potential to be taken as needed with a novel mechanism of action. Finally, the potential for a flexible treatment approach in MDD and PPD that may provide optionality to healthcare providers and patients if Zuranolone is approved. I'll note the potential for flexibility we see with Zuranolone is exactly what HCPs have been asking for to help their patients. Let me expand on the well-being and functioning data I referenced. We touched on this during our JPM presentation, but it's important to highlight in the context of the recent acceptance for filing of our NDA, as these data suggest the potential for Zuranolone to improve measures of functioning and well-being that are important for patients with depression. What you'll see here is an integrated analysis from completed placebo-controlled trials across the MDD and PPD studies showing that those treated with Zuranolone reported rapid and sustained improvements in health-related quality of life compared to placebo, as measured using SF-36 scores. These results were consistent at the day 15 and the day 42 endpoints. To summarize, these data are an important indicator as it relates to quality of life and overall health. Depression affects a person's ability to feel, think, and function. It blunts sensations of pleasure, closes off connectedness, and stifles creativity. It's important to note that patients don't want to feel less depressed. They want to feel well and get back to their normal everyday lives. Zuranolone, if approved, has the potential to help patients achieve that. We see the opportunity for people to feel well, and we know that's what matters most to patients. We also conducted interviews as a part of the open label SHORELINE study with over 30 patients who responded to 50 mg of Zuranolone and were in the study for at least six months. These interviews illustrated that a substantial majority of surveyed responders noticed improvement in their mental and physical symptoms in the first week and were satisfied by it. In addition, a majority of surveyed responders reported feeling fine, positive, or neutral about the need to be retreated, and all were satisfied with Zuranolone as a treatment. This feedback reinforces the potential positive experience Zuranolone could provide for patients with MDD and PPD if approved. I'll now move to SAGE-718, our lead NMDA receptor PAM. That is an investigational oral therapy being developed for certain disorders where impairment of cognition is one of the main drivers of disability. This is one of our wholly owned programs and was granted Fast Track designation by the FDA as a potential treatment for cognitive impairment in Huntington's disease or HD. We are also investigating SAGE-718 in people with mild cognitive impairment due to Parkinson's disease or PD, and people with mild cognitive impairment and mild dementia due to Alzheimer's disease or AD. These disorders represent some of the greatest areas of unmet need, we know that globally they continue to become more prevalent and significantly disrupt lives. On that basis, we're excited about the continued progress we've made across the program. As we mentioned earlier this year, we recently initiated the LIGHTWAVE study, a phase II study of SAGE-718 in people with mild cognitive impairment and mild dementia due to Alzheimer's disease, as well as the PURVIEW study, a phase III extension study in people with Huntington's disease. We expect data from the ongoing studies with SAGE-718 to start reading out in 2024, and we will share more detailed timelines when appropriate. We are also advancing a robust portfolio that has the potential to help patients at all stages of their lifespan. Let me provide a couple of highlights starting with SAGE-324, an investigational positive allosteric modulator of GABA A receptors. We believe that SAGE-324 holds significant potential in the treatment of neurological conditions like essential tremor or ET. We and our collaborator Biogen anticipate completion of enrollment in the ongoing phase II-b KINETIC 2 dose ranging study late this year. We're also excited about the opportunities in our early development programs, including SAGE-319, our extrasynaptic preferring GABA PAM, which we are advancing from IND enabling studies into phase I studies. We also continue to make progress with SAGE-689 and SAGE-421 and believe that they will become important pipeline contributors over the coming years. In closing, I'm proud of our progress in the Q4 and full year 2022, and I believe that we are well-positioned to execute against clinical objectives and advance our efforts to develop brain health medicines with the potential to deliver what matters most to patients. I'll turn the call over to Chris to provide additional context on our planned approach as we prepare for the potential commercialization of Zuranolone in MDD and PPD. Chris? Thanks, Jim. I'm pleased to be with you all this morning to share updates on our commercialization preparations for Zuranolone. To ensure the successful launch of Zuranolone, if approved, we made important progress last year on the commercialization front. Core activities that have enabled our state of readiness include advancing conversations with payers as permitted, with the goal of enabling access at launch, engaging and educating HCPs through meaningful scientific exchange, and hiring experienced commercial leaders to orchestrate plans intended to achieve a successful launch of Zuranolone, if approved. The recent announcement of the acceptance of our NDA filing, we remain laser-focused on preparations to execute our launch strategy. Let me outline our thinking on the potential timelines for Zuranolone. Based on our PDUFA action date of August 5th, 2023, if Zuranolone is approved for the treatment of MDD and PPD without extension of the FDA review period, we expect a potential launch near the end of 2023 following an anticipated three-month DEA scheduling review. We will be prepared and anticipate entering a market that is ready for the approval of Zuranolone. As you'll see on slide 14, we believe the opportunity in MDD is large, with millions of patients not satisfied with current treatment options. People who continue to experience unresolved symptoms of depression are at risk. Many are unable to go to work or take care of their families. It is difficult for these people to live their normal lives, and the longer they wait to treat their symptoms, the more likely they are to experience negative outcomes, such as impaired functioning and subsequent relapse. This is why rapidity matters, both in terms of initiating a therapy as soon as patients show symptoms, as well as achieving the rapid improvement of depressive symptoms. The key takeaway here is a more rapid and sustained approach to treating a depressive episode may increase the likelihood of better symptomatic and functional outcomes. Given the rapid improvements seen in clinical trials to date, we believe that if approved, Zuranolone has the potential to provide a new treatment option to patients suffering with MDD, with the goal of helping them return to a state of well-being sooner. In PPD, there is similarly a large unmet need, with an estimated one in eight mothers in the US experiencing symptoms of postpartum depression. Despite being a common mental health disorder, women experiencing symptoms may often go undiagnosed or untreated, and we see that clearly in the low diagnosis rates. Not only does PPD have an effect on a mother's overall function, but it can also have an impact on the ability for that mother to take care of her baby. These mothers and their families deserve better. Our goal with Zuranolone, if approved, is to work with the entire ecosystem to change the treatment paradigm by significantly improving diagnosis rates in women with PPD and provide HCPs with the first and only FDA-approved oral treatment indicated for PPD that has the potential to help moms get better sooner. As we enter 2023, we remain focused and diligent on our commercialization efforts in anticipation of potential launch. We continue to engage with key stakeholders in scientific exchange and are also encouraged to see positive signals from the patient advocacy community on the importance of accelerating access to innovation in mental health. As Barry mentioned earlier, we plan to be innovative on the patient access front. Our goal for this launch, if successful, is that those living with MDD and PPD who are prescribed the therapy have timely access with limited complications such as step edits and prior authorizations. In addition to our own work, we are seeing state governments across the nation make reforms to fail first policies that have historically restricted patient access to the right treatment prescribed by their physician at the right time. People with MDD and PPD deserve rapid and effective therapeutic options introduced early during treatment because early treatment is believed to deliver the best outcomes, as I've previously touched on. Given the unmet need, we believe that Zuranolone, if approved, is best positioned at launch for MDD patients requiring a first add or first switch therapy after continuing to experience depressive symptoms following their initial treatment course, including patients who have tolerability issues or noncompliance with chronic therapy. In PPD, we strive for Zuranolone to become standard of care at launch with use as first-line therapy for treatment-naive patients who are newly diagnosed with PPD or in place of other therapies currently administered. In the conversations we've had with payers, they've been highly engaged and receptive. We believe they see a role for a potential rapid-acting, sustained 14-day course oral therapy in treating both MDD and PPD. We feel an urgency to deliver a new treatment option to patients given the profound unmet need that still exists in the treatment of MDD and PPD. We are dedicated in our efforts to continue to advance Zuranolone with the goal of gaining approval and being able to offer a medicine with the potential to treat these patients rapidly and improve their symptoms. I'll turn the call over to Kimi for a review of our financials. Kimi? Thanks, Chris. Our financial results for the Q4 and full year of 2022 are detailed in our press release that we issued this morning. I'd like to take a moment to provide some context and highlight a few key points. We ended 2022 with a strong cash position, which provides us with the flexibility to support the launch of Zuranolone if approved, and strategically invest across our pipeline. Our net loss for the Q4 of 2022 was $147.1 million, and we ended the quarter with cash equivalents, and marketable securities of approximately $1.3 billion. Turning to operating expenses, R&D expenses increased to $89.3 million in the Q4 of 2022 compared to $75.4 million for the same period in 2021. The increase in spend was primarily related to ongoing investments in our wholly owned and partnered programs, including SAGE-324 and SAGE-718. SG&A expenses increased to $67.3 million in the Q4 of 2022 compared to $51.6 million for the same period of 2021. The increase was primarily related to hiring employees to support ongoing activities in anticipation of potential launch. As you heard from Chris, we're continuing preparations to support the potential launch of Zuranolone. While gaining approval and commercialization of Zuranolone remain our top priority, we're also committed to investing in our midterm and long-term pipeline in a strategic and disciplined way. To this end, we expect that our spend will increase as we continue our commercialization efforts and advance plans and ongoing studies for SAGE-718 and SAGE-324. We know that to achieve our long-term vision of transforming the care of depression, we must begin with a focused strategy and be prepared to scale quickly with success. Therefore, we remain mindful of the capital allocation prior to launch. As a reminder, as part of our collaboration with Biogen, we are jointly developing Zuranolone and SAGE-324 with a 50/50 cost sharing in the United States. Looking ahead, we are reaffirming that based on our current operating plan, we anticipate cash equivalents and marketable securities, anticipated funding from ongoing collaborations and potential revenue will support operations into 2025. Included in this guidance is the potential to achieve milestones totaling $225 million from Biogen related to the first commercial sales of Zuranolone in MDD and PPD. Given how dynamic 2023 will be, including preparing for a potential launch, we will not be providing year-end cash guidance at this time. As we embark on a pivotal year for Sage, I'm confident that our strong balance sheet will enable us to execute from a position of strength. With numerous potential value-creating milestones on the horizon for Sage, we remain focused on making strategic investments in developing pipeline programs to best position ourselves as a leader in brain health. We remain well-capitalized as we continue to build a strong team executing on objectives across our pipeline. The time is now for patients. We are optimistic that our approach will lead to the development of treatments that people are desperately waiting for. I'll now turn it over to Helen to handle Q&A with the operator. Helen? Thanks, Kimi. Before I turn it over to the operator, I'll ask that you limit yourself to one question. If you have an additional question, feel free to return to the queue. I'll turn it over to the operator to handle Q&A. Operator? Thank you. If you would like to ask a question, please signal by pressing star one on your telephone keypad. If you are joining us today using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, that is star key followed by the digit one. We'll pause for just a moment. At this time, we'll hear from Tazeen Ahmad from Bank of America. Please go ahead. Hi. Good morning. Thanks for taking my question. Just wanted to clarify something that was said in the prepared remarks. I think, Barry, you said that, post the PDUFA in August, you expect to be able to launch Zuranolone if approved, by the end of the year. What would be rate-limiting factors that would prevent you from immediately launching, and can you just narrow down when you think you would be able to start recording sales? Would it be in calendar 2023, or would we assume it should be more in 2024? Thanks. Tazeen, thank you and thanks for the question, the attention. Look, we're really excited that the FDA has accepted the NDA filing for Zuranolone for MDD and PPD with a PDUFA action date of August 5th, 2023. Well, I'll remind you that following approval, if it occurs on August fifth without delay, we then move to a three-month DEA scheduling period. There are actions we can take during that period, but we can't start selling Zuranolone recording sales until we have that official label with the DEA schedule. That'll happen toward the end of the year, and we'll be very well prepared to launch and excited to do so. We'll move next to Salveen Richter from Goldman Sachs. Good morning. Thanks for taking my question. With regard to the payer work here, could you just comment on their understanding of pricing a drug, you know, at an annual price for a, once a year, you know, two-week period or using it maybe twice a year? Secondly, I think the commercial payer mix is about 51% of the payer mix. When you think about DBA and the strategy here, how effective are those gonna be to kind of help you know, position the drug with the physician, with the physicians, in terms of adopting a new treatment paradigm? What do you do with the remainder of the, you know, kind of non-commercial payer aspect? Yeah. A few different aspects in there. One, I'll start, and then I'll ask Chris to comment further. In terms of the proactive value-based agreement strategy that we advise and are employing, the concept for us is to help payers with some budget certainty. That's really what they want. They know that depression is not well managed, and Chris will get into that in a bit. They want budget certainty. In return, we want, if a physician or healthcare provider believes that a patient requires Zuranolone and writes a script, we want that script filled quickly. That's sort of the exchange there, and there's more detail to that we can get into, but that's sort of the high level. In terms of what we hear from payers, from a pricing perspective, is that they think about per patient per year. They're not thinking about per pill, per pack. They're really focused on understanding, per patient per year. Chris, you wanna comment further? I think the DBA piece to this, Barry, is just frankly one component. I think to be truly transformational, we have to be accessible, and that really starts with payers in and around understanding unmet need. I think in all of the interactions that we've had so far, there's a high understanding of unmet need in and amongst the payers and truly a perception that they need something that works quite differently than what they've seen historically. They've been impressed with the data, and I think they certainly understand from those interactions the opportunity that Zuranolone presents to deliver something that works, you know, in a rapid-acting fashion after just three days, a 14-day course, something that's durable over time, doesn't come with the stigmatizing side effects so often associated with other therapies, and actually has the potential to return patients to a state of well-being. In a sense, it takes a very complicated patient type and makes it far simpler to manage than historically what they may have had at their disposal. Incredible excitement around that, which shapes the conversation around proactive value-based agreements. I think in and around the second question around payer types, you know, we're gonna work with all different payer types regardless of the mix that they see to come up with solutions to making sure that Zuranolone is accessible at launch and again, to really build on that understanding of unmet need and what Zuranolone can deliver from what we've seen in the data so far from both LANDSCAPE and us. Thank you. Moving next to Anupam Rama from J.P. Morgan. Hey, guys. Thanks so much for taking the question. Maybe expanding on some of your comments in the introductory remarks here, how are you thinking about sort of the initial ramp curve in PPD, and what are some of the pre-commercial sort of education activities you're doing in particular with the OBGYN segment? Thanks so much, guys. Yeah. Anupam, great to have you on board and great question. Let me ask Chris to talk about the overall approach to PPD and how we're educating in appropriate scientific exchange, OBGYN, GYNs and others. Yeah. As you might imagine, there's a lot of focus on PPD within the organization. I think, you know, if you pick up the newspaper or you go online, you see that just like MDD, there is a significant mental health crisis occurring with moms from postpartum depression. You know, in fact, we're talking about 500,000 or so cases of PPD on an annual basis, or one in eight live births. It's absolutely paramount that we continue to do the work that we're doing in and around working with OBGYN and other prescribers that also see patients that are suffering from PPD to help understand the importance of diagnosis or screening and diagnosis, and subsequently the opportunity that a new therapy potentially like Zuranolone offers to them as it would be the first and only FDA-approved oral therapy for the treatment of postpartum depression. You know, we believe that through the permitted scientific exchange that's happening right now through our medical affairs team, and whether it's at congresses or one-on-one interactions with key opinion leaders, we're gonna continue to heighten the sensitivity and urgency around the need to treat moms that are suffering with PPD. We believe that community, the OBGYN community, will be ready at the launch of the product and will happily receive Zuranolone, as I said, as the first and only orally oral therapy after the FDA approves. Just to round that out, Anupam, when you launch a readily available oral medication like we plan on doing for Zuranolone if it's approved, this is exactly the kind of paradigm shift that happens in medicine. As Chris mentioned, about a half a million moms per year, are purported to have PPD. Less than 20% of those are diagnosed, and even less are treated. That's really because of the challenging to get diagnosis and treatment. When you have an agent like Zuranolone that works quickly with a 14-day regimen, we see the opportunity for physicians to look more rapidly for the diagnosis of PPD and certainly more readily treat it. This is exactly the kind of medicine that changes the diagnostic paradigm in a disease like PPD. Ritu Baral from Cowen, your line is open. Good morning, guys. Thanks for the update today. I wanted to just ask about the SHORELINE data contained in the submission. Can you guys confirm that, you know, what we have in the public domain is sort of the extent of the SHORELINE follow-up and retreatment data contained in the dual NDA? Can you give us any color as to what will be presented additionally from SHORELINE midyear? Thanks. Yeah. Thanks, Ritu. Jim, you wanna take that? Yeah, of course, Barry. The Shoreline study, naturalistic site design, designed to follow patients with MDD and evaluate both safety and tolerability of Zuranolone and the need for repeat dosing for up to one year. The Shoreline study has multiple roles in the program. First and foremost, it provides us with safety data for well over 1,000 patients now. Equally important, it provides some real-world evidence for how Zuranolone may be used if approved. The Shoreline is an important component in the NDA submission. The data that's completed to date is included in the NDA submission. The Shoreline study also continues, so we have the newest cohort of Shoreline, which is completing now. That cohort is a rollover cohort from the CORAL study. That will provide some really additional interesting information, for retreatment with Zuranolone. The Ritu, the data that you've seen today on SHORELINE, as we presented multiple times, is in essence, what's in the NDA filing, as Jim said, will be used largely from a safety database. We'll have an update midyear, which we think will be quite informative. When we get that update, we'll let you know. Great. Will that update be submitted to FDA at that time? There's regular communications with FDA on data updates, including SHORELINE. Awesome. Thank you. Thanks, Ritu. We'll hear next from Yasmeen Rahimi from Piper Sandler. Good morning. This is Swapnil on for Yas. Thank you for taking our questions. First one is if you could provide a little bit of more color on the lifecycle innovation study that you mentioned in the press release, related to design details and the timing of that study. Second one is, when should we expect to see the health economic data for the LANDSCAPE and the NEST studies? Yeah. Swapnil, thank you. Please send our best to Yas. Jim, you wanna take that? Absolutely, Barry. At the moment, we're not providing any additional details on the lifecycle management study. The HER data that you're referring to, there's a lot of additional data for Zuranolone that is coming out in key publications and scientific conferences throughout 2023. Thank you. I think we can move to the next question. We'll hear from Ami Fadia from Needham. Hi. Good morning. This is Ethan Ong for Ami. Thanks for taking our question. You know, Biogen's comments on its earnings call yesterday, you know, continue to be positive on the Zuranolone opportunity. Maybe could you provide, you know, some more details on how y'all and Biogen are kinda working together with regards to things like prepping the market, communicating with FDA, payers, et cetera? Thank you. Ethan, thanks for the question. Biogen from the start has been a phenomenal partner. Clearly with Chris Viehbacher coming on board, given his experience in leading large organizations, his leadership in pharma as well as experience with depression, has really been an add to an already strong partnership. Together, we're very bullish on the opportunity for Zuranolone to help millions suffering from MDD and PPD. We're like-minded in terms of the paradigm shift we're looking to create in the treatment of depression. I'd say from a, you know, a regulatory development, commercialization, CMC, supply chain perspective, we're step in step in how we're working in the U.S., and it's a 50-50 [cautionary] in the U.S. We're well prepared together, if approved, to launch Zuranolone. We'll move next to Jay Olson from Oppenheimer. Oh, hey. Congrats on the progress, and thank you for the update. Can you remind us what level of DEA scheduling you're expecting to receive for Zuranolone and how the scheduling will impact the launch of the drug and physician and patient perception in Zuranolone? Thank you. Yeah, Matt, thanks for the question. Given the class of medicines that Zuranolone is a neuroactive steroid targeting GABA, we anticipate that we'll be a Schedule IV drug. The three-month DEA review after our approved action date, assuming we're approved, will be the process to confirm that. What people need to understand is that the drug schedule has a lot to do with supply chain management and how these agents are handled across the supply chain, raw materials, active ingredients, as well as how it's handled in the pharmacy. In terms of patients getting a prescription from their physician, virtually every physician has a DEA number to write, and there's millions and millions of prescriptions being written for scheduled drugs by our target audience already. We really don't see it being an issue at all. Great. Thank you very much. Thanks, [much]. Laura Chico with Wedbush Securities, please go ahead. Hey, good morning. Thanks for taking the question. I wanted to circle back to one that's a little bit more logistical, but on the commercialization. Any additional commentary around kind of how you envision patient management or patient flow management is gonna be handled in the commercial setting? I guess what I'm trying to understand a little bit more is who in the offices is gonna be primarily responsible for managing patient follow-up patterns. I'm trying to understand a little bit more on the refill process. How are they going to be monitored, and what would trigger a refill to be authorized? Thanks. Yeah, great, Laura. That's a really important question. We think Zuranolone doesn't change the practice of psychiatry or primary care that treats these folks. It really enhances. It's another tool in the tool belt where they'll understand if patients are managed or patients respond more rapidly than the tools they have today. Let me ask Laura, who's treated a bunch of these folks, on how she thinks about the patient flow. Yeah. Thank you for the question. You know, it's my belief that Zuranolone, if approved, is really gonna fit in with how HCPs are currently treating patients with depression. I think that they will continue to monitor patients over time, and if there is a reemergence of symptoms that suggests another depressive episode is occurring, then they will undergo another treatment course with Zuranolone or another appropriate agent, depending on the physician and patient conversation. I think what Zuranolone really brings to the table here is a tool that is different than the tools that physicians have been able to use in the past. It is a drug that works rapidly, that has a durable effect, and that is a short-term treatment course. From discussions with physicians, what we hear is that these are things that are really highly valued and will really be an important part of the armamentarium to treat depression moving forward. Yeah. Just to round that out, because some of the basis of your question, Laura, is sort of a common belief, which is a misconception, that today a patient comes in, they are put on a chronic medication. They stay on that medication and maybe get followed up at six months and all is well. The data don't support that. The data suggests that a patient given a new antidepressant is only on that antidepressant for a median of seven weeks and that patients who continue to seek treatment, and some don't, some discontinue continuation and leave the system, but those that continue to seek treatment, flow through two to three different medications within a year. Just think about it. It's not like today someone's on a chronic med, and they're just fine. They're not. We think Zuranolone with the potential rapid effect, again, as Laura said, enhances the practice of treating that patient. It doesn't really change how you monitor that patient. you also asked about refills. There'll be a variety of ways that refills can happen. Some might write a script for Zuranolone with a refill already, instructing their patients that if they're feeling better for an extended period of time but they're dark in mood, elevated anxiety or insomnia come back, do the refill and try it again. If it doesn't work, come and see me, I might have other tools for you. A refill can be called in to a pharmacy, just like any drug today. Thanks. Moving next to Sumant Kulkarni from Canaccord. Please go ahead. Good morning, thanks for taking my question. Zuranolone is relatively rapid acting. Either in SHORELINE or in any other setting, do you have any data on patients that may have stopped taking the product before completing the full 14-day course of therapy simply because their episode of depression had gone away, and they were feeling better? I'm asking because this discretionary patient action could have important implications for pricing and potential sampling, and the dynamic might lead to large distributions around the per patient per year pricing that payers are looking at versus maybe setting a flat price. Yeah. Sumant, thanks for the question. I'll ask Jim to talk about the specific data. There, you know, obviously, when you're treating over 3,500 patients, there are probably some patients who took a drug for a period of time and stopped because they're feeling so better. That's in large part not what's happening. Just like, if you are prescribed a Z-Pak for your lower respiratory tract infection and told you'll feel better but complete the full course, that will be the instruction for Zuranolone. We don't really believe there's gonna be much of a dynamic where a patient might take Zuranolone for three days or four days and, quote, unquote, "save the rest of their pack for another episode." There will be instruction to complete the 14-day pack. The data are supported that those that complete the two-week and respond, remain responded. We don't really think that's gonna be a big dynamic that plays out here. We'll hear next from Yatin Suneja from Guggenheim. Hey, guys. Thank you for taking my question. Just following up on a question that they asked earlier. The profile of the drug is short term, and you have a DEA scheduling to probably limit your ability to sample. Can you maybe just talk about the relevance of sampling? How could that impact you, especially in the PCP setting? Thanks. Yeah, yeah. Thanks for the question. Let me ask Chris to talk about our overall approach there. From what we're thinking about, there's a number of different ways that we think about getting physicians really experienced with the medication. While we haven't communicated yet that we're going to have an extensive sampling program, there's a number of different ways to think about this, and the team is really thinking through that. We know that from the experience that we've seen with investigators is that those physicians that have experience, they recognize the profound impact that Zuranolone has. That early experience is going to be critical. With respect to DEA scheduling, we don't anticipate it having a major impact on the way that we think about sampling. While there may be one or two states that may have some language around sampling and sampling storage, there's alternative ways to get physicians experienced with it. We don't see DEA scheduling as being something that would in any way inhibit a physician from getting early experience. Quite in fact, we think that from the vast array of programs that we can employ, the early experience is gonna be something that's gonna have a profound impact on the launch of the medication. Tim Lugo from William Blair has your next question. Thanks for taking my question. For the launch, are you gonna set up a central hub to deal with any pre-authorization or access hurdles physicians may have to deal with, during the early parts of the launch? Yeah, Tim, thanks for the question. Look, we advise we have a very robust channel strategy in place that deals with everything from to the extent there's prior author steps to make sure that if a script is written, that patient gets the drug. Look, that will all be set up and in place. Okay, great. Thanks, Tim. We'll move next to Neena Bitritto-Garg from Citi. Hey, guys. Thanks for taking my question. I actually just had a question on the KINETIC 2 study. I was just wondering if you could give us an update on what you're seeing on the enrollment front there, and if some of the measures you took to speed up enrollment have resulted in a faster pace? Thanks. Thanks, Neena, for the question. Jim, you wanna take that? Yeah, of course. Thanks, Neena. As you mentioned, we're currently very focused on completing the KINETIC 2 phase II-b study for essential tremor in the Sage -32 4 program. The KINETIC 2 study is currently open for enrollment, and we're anticipating completion of enrollment in late 2023. As I've spoken about previously, a number of factors have challenged the KINETIC 2 study. One of those was clearly some staffing challenges at sites and CROs coming out of the pandemic. That's something that's being seen across the industry. We also saw a little bit of a slower pace of enrollment than we had originally anticipated due to some specific criteria in the protocol. Finally, there are multiple ET trials that are targeting a similar patient population that are going right now. We, as we mentioned previously, we made some modifications to the program, and we're confident that those modifications are having a positive impact. As I say, we expect to complete enrollment in late 2023. Douglas Tsao from H.C. Wainwright, please go ahead. Hi, good morning. Thanks for taking the question. Just curious, how do you plan or do you plan on doing a post-marketing study, and I'm just in order to understand how frequently patients need to be treated with Zuranolone, obviously just given the fact that patients switch payers a lot, and so forth, and obviously there's sort of, you know, limitations with like IQVIA and so forth data. Just curious, how do you over the long-term plan to understand the profile and how frequently patients need to be treated? Thank you. Yeah. Thanks, Doug. That's a, that's an important question. What we know today, and Jim commented on this earlier, is, you know, SHORELINE is the largest naturalistic study in depression run to date to our knowledge. The data are pretty clear. Now, while SHORELINE isn't exactly real world, it's close to real world as we can get at this point. What we see for SHORELINE is for those that responded, the majority required only the initial two-week course of treatment. If the number is 80% required either one or two course of treatment in the calendar year. We believe that that's how it's gonna play out in the real world. Once we're launched and approved, we'll certainly work a number of different ways to understand what's happening over time, whether it's registries, or payer collaborations. We'll have those data at hand. Because we will have value-based agreements in place, those will be informative as well. There'll be a number of sources for us to understand how many two-week courses a population needs over a period of time. You know, physicians, do you get a sense, are they gonna use Zuranolone initially as an add-on, or do they wanna use it as a monotherapy as sort of a switch? In the scientific exchange that we have with potential prescribers and our investigators, we're hearing different views. The good news is that we have data with Zuranolone as a monotherapy on top of a stable antidepressant and co-administered with antidepressant. We have a profile with Zuranolone to use the medicine as the patient feels appropriate for as a physician feels appropriate for their patient. You know, we've heard some physicians for certain patient types like young adults, they might wanna use it as monotherapy. For someone that frequently suffers from depressive episodes, they might wanna prescribe it as a co-administration. We have the optionality and the data to support the way a healthcare provider thinks best to treat their patient. Great. Thank you very much. We'll move next to Marc Goodman from SVB Securities. Thanks for taking my question. This is Rudy on the line for Marc Goodman. I have two questions for SAGE-718. The LIGHTWAVE and DIMENSION study use an initial higher dose followed by lower dose, while the other two study uses fixed dose at 1.2 mg. Can you talk about the rationale for the dosing selection? Secondly, can you talk about the difference- Between patients that using inpatient versus outpatient settings. Thanks. Yeah, Rudy, thanks for the question. Look, we're really excited by SAGE-718 as the first-in-class NMDA-PAM that we're studying for cognitive impairment across neurodegenerative diseases, including Huntington's, Parkinson's, and Alzheimer's. The program's progressing very well. We're really excited to have data from that program in 2024. In terms of your specifics, Jim, you wanna talk about the dose in inpatient? Absolutely, Barry. As Barry said, we're very excited about SAGE-718. We're currently running five phase II studies across three different indications, Huntington's disease, Parkinson's disease, and Alzheimer's disease. Really, the dosing that you're referring to. Well, the strategy is to achieve and maintain a certain level of exposure for SAGE-718. What you're seeing is, as the program matures, we are doing that. The goal is in the case of the DIMENSION study, which is dosing for over a three-month period to achieve and maintain that dosing level. We are at this point looking at outpatient studies for the SAGE-718 program. The profile of SAGE-718, both from a safety and PK perspective, really allows us to do that. All these studies are outpatient studies. Yeah, I would just add in Rudy that the benefit risk we're seeing for SAGE-718 is extremely broad. you know, we're seeing rapid improvement in higher order cognition, executive function, learning and memory, and an incredibly clean tolerability profile. We're really excited about continuing to move that forward. Got it. That's very helpful. Thanks. Thanks, Rudy. Gary Nachman from BMO Capital Markets, your line is open. Hi, good morning. With the priority review for Zuranolone, do you still think there's a possibility for an AdCom? Does that change at all with priority review timeline, and when would you find that out? The way the NDA has been filed, you're obviously looking for an approval in both MDD and PPD together. Is it possible for the FDA to split those up and approve one indication first, and then the other at a later point if it ultimately wants to see more data? Thanks. Hey, Gary. Thanks for the question. Let me take the second part first. As you highlighted, we filed an NDA for both MDD and PPD, and we think the data warrant approval for both MDD and PPD. That's our current thought at the time and advise as well along with that. In terms of an AdCom, that's solely at the discretion of the FDA. You know, if the FDA decides to hold an AdCom, we would be excited to showcase the totality of the Zuranolone data. As typical in AdComs, hear from patients and patient advocates to highlight the really, you know, devastating unmet need that continues out there with depression. We'll be well prepared if they have an AdCom. If the FDA decides not to hold an AdCom, and that's a signal of a faster approval, we'd like that too. Moving next to Brian Abrahams from RBC Capital Markets. Hey, guys. Good morning. Thanks for taking my question and congrats on all the progress and on the filing acceptance. I'm curious if you could talk about your latest views on how you might gate the launch focus and investment, from targeting psychiatrists initially, to ultimately moving and expanding into the primary care setting. Curious what feedback and metrics you might be looking for to shape that potential progression. Thanks. Brian, thanks for the question. Thanks for the congratulations. Glad to hear that you're as excited as we are. Look, we live in a world of really strong information and have really good knowledge of those healthcare providers that are seeing depression patients, those that are willing to write prescriptions, particularly branded prescriptions. We advise and will focus on where we think we'll get the strongest patient flow that has the right kind of insurance coverage first, and then expand rapidly with success. That's the approach we're taking. We're certainly gonna focus on psychiatry and those larger offices, irrespective of discipline, that see a lot of these patients. That'll be our focus. Chris, anything to add? Yeah. I think there's a note, and I think we've communicated this in prior calls, is there is a group of PCPs that you'll be calling on at launch. These are PCPs that do behave more like psychiatrists. They see a number of patients with MDD. We'll also focus on OBGYNs, right? I don't want the piece about PPD to be lost. I think as you said, it's very based on the metrics that we have, both physician-level and patient-level data that we have at our disposal. We're gonna make decisions at the right time to continue to scale with success as we move forward. Yeah. I'd also add, Brian, that we're able, again, in the world we live in to understand patient activation and the kind of patients that are frankly gonna ask for Zuranolone by name. We believe that that's gonna happen with a drug like this. Thanks so much. Danielle Brill from Raymond James, your line is open. Hey, guys. This is Alex, on for Danielle. Thanks for taking our question. I know you're not targeting treatment-resistant depression in your commercialization strategy, but do you feel that it's a risk for clinicians to initially trial Zuranolone in their patients that might skew towards this population, potentially negatively coloring their perceptions of efficacy? Like, in other words, do you think Zuranolone would work in TRD? Just on that front, what's the gating factors now to initiating formal trials in treatment-resistant depression, anxiety, bipolar? Thanks. Let me start with the second part of that. I'll talk about it first. We believe the unmet need in MDD and PPD is so great. You know, as we talked about, 6-7 million dynamic patients with, looking for new treatment, options in MDD. Half a million moms that should be diagnosed with depression a year. That patient population is so significant, unmet need so significant, that will remain our focus for the foreseeable future. If we can win in depression, we can really help millions of patients. We'll provide sort of future indications at later points in time. Right now the focus is absolutely win in depression, try to help as many people as we can. In terms of how at launch the drug will be used, as Chris already highlighted, in PPD we'd like to have Zuranolone be standard of care, the only oral... if approved, the only oral treatment approved specifically to treat PPD. In MDD, our target is to educate physicians that Zuranolone should be used as your first switch or first add-on should a patient not be adequately controlled with whatever they're taking. That will be our first area. Quick thing to add? Yeah. I think what I'd add to that, Alex, is, you know, if left to things to just happen, I could see where physicians, you know, across all different areas of treatment use new products later. Here what we have through not only the positioning and the identification of appropriate places of use is the idea of proactive value-based agreements. Proactive value-based agreements are designed to really ensure that physicians have access earlier in the treatment paradigm so that you don't have the onerous prior authorizations and step edits, which can ultimately take a new medication and push it to later utilization. That's why it's so important that we work across all stakeholder groups to make sure that physicians have the ability to really access early in the treatment process and use it where they want to use it at launch. We'll hear next from Joon Lee from Truist Securities. Hi. Thanks for taking our questions. Looking forward to additional data, from SHORELINE midyear. Is that something you'll be submitting to the FDA as part of the NDA package? Also quickly, you mentioned lifecycle management for Zuranolone. Can you share what you have in mind? Thank you. Yeah, Joon, thanks for the question. We're not commenting more on lifecycle management. As we commented earlier on the call, we'll have a regular series of updates with the agency, including Shoreline. Thank you, everyone. That will conclude the Q&A portion of today's call. With that, I will turn it back over to Mr. Greene for closing remarks. Thanks, Lynette. Thanks again to everyone for joining us this morning to review our Q4 and full year 2022 results. Our progress in the Q4 and throughout 2022 is the direct result of teamwork and dedication from everyone in our and our partners' organizations. I wanna thank everybody. As we make critical advancements progressing development activities across brain health, we maintain a position of strength as we advance our mission to develop and launch transformative medicines for patients in need. Thanks again, everyone, and have a wonderful day. That does conclude today's telephone conference. Goodbye. We thank you all for your participation.