Good morning. Welcome to Sage Therapeutics conference call to discuss top-line results from the SKYLARK study. Currently, all participants are on a listen-only mode. This call is being webcast live on the Investors and Media section of Sage's website at sagerx.com. This call is the property of Sage Therapeutics, and 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 like to introduce Helen Rubinstein, Director of Investor Relations at Sage. Good morning, and thank you for joining Sage Therapeutics conference call to discuss top-line results from the phase 3 SKYLARK study of Zuranolone in postpartum depression. 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 and slides related to today's call. I'd 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 consult the risk factors discussed in today's press release and in our SEC filings for additional details. We'll begin the call with prepared remarks by Barry Greene, our Chief Executive Officer, who will provide an overview of this morning's announcement. Barry will then be joined by Jim Doherty, our Chief Development Officer, who will review the data in more detail, and Chris Benecchi, our Chief Commercial Officer, who will share some context on our planned approach to commercialization in PPD if Zuranolone is approved for that use. Kimi Iguchi, our Chief Financial Officer, will join for the Q&A portion of the call. I'd now like to turn the call over to Barry. Thanks, Helen, and thank you everyone for joining us this morning. I'm thrilled to be with you all to review the robustly positive results from the phase 3 SKYLARK study of depression or PPD. I'll begin by discussing the key highlights from the study. Then, as Helen said, I'll turn the call over to Jim to walk through the results from the SKYLARK study in greater detail and Chris to share some context on our planned commercialization approach if Zuranolone is approved. As you may have already seen from our press release with our collaborators at Biogen, the SKYLARK study met its primary and all secondary endpoints. Results of the day 15 primary endpoint were very robust, with Zuranolone 50 milligrams demonstrating a statistically significant and clinically meaningful reduction in HAMD-17 score compared to placebo. Zuranolone 50 milligrams also demonstrated statistically significant reductions in HAMD-17 total score compared to placebo at all measured time points throughout the study. In fact, a statistically significant and clinically meaningful reduction in HAMD scores were seen as early as day three, the first measured time point, and continued through days 28 and 45. We also saw stat sig improvement in the CGI-S score with Zuranolone 50 milligrams compared to placebo at day 15. These results reinforce our belief in the potential for the rapid onset and sustained effects of Zuranolone in treating PPD and reinforce the overall data we've seen in over 3,000 patients in PPD and MDD. Additionally, Zuranolone 50 milligram was well-tolerated in the SKYLARK study, demonstrating a safety profile in the trial consistent with that seen in other trials with the NEST and LANDSCAPE programs to date. With the positive results from the SKYLARK study, we believe that data generated to date support the potential of Zuranolone to become the future standard of care for PPD. Our aim is to gain FDA approval to be able to offer this innovative treatment option with the goal of reducing negative impact PPD has on women and their families that can last for generations. PPD is one of the most common medical complications during and after pregnancy. An estimated one in eight mothers, or approximately 500,000 women in the United States, report experiencing a symptom, symptoms of PPD each year. This is an area of significant unmet need. If left untreated, symptoms of PPD may persist for months or years and may have devastating consequences for the mother, child, and family, with potential generational impact. Notably, PPD symptoms can be associated with significant impairment in mother-infant bonding and maternal function, including breastfeeding and caring for the child. Children of mothers with PPD symptoms are at a long-term heightened risk for negative behavioral, cognitive, and psychological outcomes throughout childhood into adulthood. To avoid a generational impact, it's clear that women need timely access to innovative treatment options for PPD. We believe that with Zuranolone, we have an opportunity to offer treatment options that may help to address this unmet need. If approved, Zuranolone will be the first oral medication specifically indicated to treat PPD. Looking forward, we've begun the NDA submission for Zuranolone MDD, which we expect to complete in the H2 of 2022, and we remain on track to submit an associated NDA to the FDA for Zuranolone in the treatment of PPD planned for early 2023. We believe that the results shared today provide meaningful evidence that reinforces the profile of Zuranolone demonstrated across clinical trials to date. The SKYLARK study marks the seventh positive clinical trial evaluating Zuranolone in PPD and MDD. The data to date continues to show a consistent clinical profile that includes rapid and sustained antidepressants effects with a well-tolerated short course treatment. We believe that a rapid-acting, long-duration, short-course oral treatment that's well-tolerated provides the attributes that people with MDD and PPD tell us they want most of the treatment, and we look forward to continuing our work aimed at bringing this important innovative treatment option to patients. Before I turn the call over to Jim, I want to thank the participants of the SKYLARK study, their families and caregivers, the trial investigators, everyone on the clinical site, and importantly, all the people at Sage. Whose dedication to this program has been vital to our success. With that, I'll turn the call over to Jim to discuss the results in more detail. Jim? Thanks, Barry, and good morning, everyone. I'd like to reiterate our thanks to the study participants, their families and caregivers, the trial investigators, everyone at the clinical sites, and Sage employees and collaborators for their contributions to the Skylark study. A tremendous amount of effort goes into the successful conclusion of a clinical trial. We're grateful for those who have invested so much time and energy in making this moment possible. I'll now walk through the data we shared this morning. Starting on slide 4, I'll begin by reviewing the Skylark study design. The Skylark study was a phase III randomized double-blind placebo-controlled trial assessing the efficacy and safety of Zuranolone 50 milligrams compared to placebo in adult women with PPD. The study enrolled women with HAM-D scores at or above 26 at baseline. The 200 patients enrolled in the study were randomized to receive Zuranolone 50 milligrams or a placebo once nightly for 14 days. After the treatment period, people in the study were then followed for an additional four weeks. The primary endpoint in the SKYLARK study was the change from baseline in HAMD-17 total score at day 15. The key secondary endpoints were the change from baseline in HAMD-17 total score at days three, 28, and 45, as well as change from baseline in the CGI-S score at day 15. As a reminder, Zuranolone is a next generation positive allosteric modulator or PAM of GABA A receptors that is in development as a potential first in class oral treatment for MDD and PPD. Turning to the efficacy results from the SKYLARK study. As you can see on slide 5, Zuranolone 50 milligrams demonstrated a statistically significant and clinically meaningful reduction in depressive symptoms compared to placebo, as measured by change from baseline in HAM-D-17 at day 15, the primary endpoint. The least squares mean difference at day 15 was four points with a p-value of 0.0007. We're excited by these results, which we believe demonstrate the robust reduction in depressive symptoms seen with Zuranolone treatment in this trial. As Barry mentioned, Zuranolone also met all key secondary endpoints in the study. Turning to slide 6, I'll review those findings in additional time points. As you can see from this slide, Zuranolone 50 milligrams demonstrated statistically significant and clinically meaningful reductions in depressive symptoms compared to placebo, as measured by change from baseline in HAMD-17 at days three, 28, and 45, with highly significant p-values at each time point. We believe these results reinforce the data seen in other studies in the LANDSCAPE and NEST program, demonstrating a rapid onset of reduction of depressive symptoms that was sustained throughout the follow-up period. Importantly, these results further validate findings from other studies with zuranolone across PPD and MDD, showing that patients who responded to zuranolone maintain that response through the follow-up period, well after zuranolone treatment course had concluded. The other key secondary endpoint was change from baseline in the CGI-S at day 15, which is shown on slide 7. The CGI-S is a clinician-administered 7-point scale which rates the severity of a person's disease at the time of assessment. At day 15, Zuranolone 50 mg demonstrated a statistically significant and clinically meaningful improvement in CGI-S score compared to placebo with a p-value of 0.0052. Turning to safety results on slide 8. The study showed that Zuranolone 50 mg was generally well-tolerated and demonstrated a safety profile consistent with other trials in the LANDSCAPE and NEST program to date. The most common adverse events occurring in 5% or greater in patients in the Zuranolone 50 mg arm were somnolence, dizziness, sedation, headache, diarrhea, nausea, urinary tract infection, and COVID-19. These findings support the safety profile of Zuranolone that we've seen in the clinical program to date. The majority of treatment-emerging adverse events reported in the study were mild or moderate in severity, consistent with prior Zuranolone trials. Importantly, there were no signals for increased suicidality or withdrawal symptoms in the study as measured by the Columbia-Suicide Severity Rating Scale and the 20-item Physician Withdrawal Checklist, respectively. Turning finally to slide 10. In summary, we're incredibly excited about the results from the SKYLARK study. These data support the differentiated profile Zuranolone has demonstrated to date in seven positive clinical trials in PPD and MDD. Based on that totality of data, we believe that, if approved, Zuranolone may provide a unique treatment option for people suffering with PPD and MDD. A treat as needed approach for depressive episodes with the potential for rapid onset and sustained antidepressant benefit. These results from the SKYLARK study complete the set of placebo-controlled trials set out in the LANDSCAPE and NEST programs. We look forward to updating you with more details from the SKYLARK study in the coming months. I'll now turn the call over to Chris to provide context on our planned go-to-market approach in PPD if zuranolone is approved. Chris? Thanks, Jim, and good morning, everyone. I'm pleased to be here today to share more detail on our planned approach if zuranolone is approved to help women with PPD. Starting with slide 10, as you heard from Barry, it's clear that there's tremendous unmet need in PPD and that women suffering from PPD deserve urgent medical treatment. In fact, if left untreated, PPD can be devastating for mothers, babies, and their families with impact that can last for generations. There are a few critical points I'd like to highlight on the potential consequences of untreated PPD. First, mothers with PPD often face challenges bonding with their infants. Additionally, they may feel overwhelmed and anxious, feel isolated, and feel that they've lost their identity. Second, mothers with PPD are at a higher risk for suicide and substance abuse. Unfortunately, in the U.S., suicide is a leading cause of pregnancy-related mortality. Third, if left untreated, PPD can result into persistent depressive symptoms and prolonged maternal morbidity and mortality, including harm to the child. What's often overlooked when discussing PPD is that the burden of illness extends to the child, the family, and the healthcare system, as shown on slide 11. Undiagnosed PPD in a mother can result in long-term emotional problems for the child, such as delayed or impaired developmental, psychological, cognitive, and physical outcomes throughout childhood and into adulthood. PPD also puts a strain on family relationships, and this burden extends to society. From the perspective of the healthcare system, households of women with PPD experience an estimated 22% higher healthcare costs than those of women without PPD. New accessible treatment options are desperately needed for postpartum depression. Slide 12 highlights the urgency in treating PPD, which I'll remind you, is one of the most common medical complications during and after pregnancy. In the United States, an estimated one in eight women experience PPD symptoms, equating to about a half a million women. Of those who experience PPD symptoms, only about 28% are actually diagnosed with PPD. These women deserve a treatment option that allows them the potential to return to feeling like themselves and to bond with their babies. That's why the results we shared this morning from the SKYLARK study are so compelling and meaningful. The SKYLARK study further reinforces the profile of that we've seen in clinical trials to date, which is shown on slide 13. We're excited by the opportunity this compelling profile may offer to help women with PPD. To that end, if approved, we expect that successful commercialization of Zuranolone in PPD will require an approach that is designed to educate and engage stakeholders, including patients, HCPs, payers, patient advocates, and policymakers. Our goal will be to create a positive experience for these women with PPD who are prescribed Zuranolone. We plan to help mobilize HCPs in partnership with patient advocates and policymakers to utilize available risk screening tools so all mothers can be screened and those who are experiencing PPD can be diagnosed and treated with urgency. Finally, we plan to drive awareness of unmet need among payers and employ an access strategy that minimizes barriers for women who are prescribed Zuranolone. The positive results from the SKYLARK study shared today bring us one step closer to our goal of being able to help mothers suffering from PPD by offering Zuranolone as a novel first-in-class oral treatment option. I look forward to sharing more detail on our plans for potential commercialization in both PPD and MDD in the coming months. With that, I'll now turn the call over to Helen to handle Q&A with the operator. Helen? Thanks, Chris. Before I turn it over to the operator, I'll ask that you limit yourself to one question. If you have an additional question, please feel free to return to the queue. Now I'll turn it over to the operator to handle the Q&A. Operator? If you'd like to ask a question, please press star then one. If your question has been answered and you'd like to remove yourself from the queue, press the pound key. Our first question comes from Yasmeen Rahimi with Piper Sandler. Your line is open. Good morning, team. Thank you so much. Maybe two quick, one clarification question. Could you comment on what were the rates of discontinuation in the study in the SKYLARK? Then two, when we compare the data to ROBIN, it's really perfectly aligned. However, the somnolence and sedation rates as expected are slightly higher in the SKYLARK given it's a higher dose group. I guess the question for you here is, as you're thinking about filing in PPD, would you be moving forward with the 50 mg dose group or actually decide to go with 30 because it seems like you're not getting an additional benefit with 50? Sorry for the long-winded question. Appreciate any comments you have for me, and thank you for taking it. Thanks, guys. This is Jim. Appreciate the questions. You know, I think a couple of points around discontinuations. We're seeing discontinuations across all causes really pretty much balanced between placebo and the drug arm. About 12% in the placebo arm, about 14% in the drug arm. I would say importantly, discontinuations due to adverse events about 1% in each arm. You correctly point out that compared to the earlier ROBIN study, the frequency, the percentages for adverse events like somnolence and sedation are a little bit higher. I'd say very consistent with what we've seen from other studies with the 50-milligram dose, so very consistent across the program. I think, you know, thinking about dose for the PPD indication, I think what we've got now is two very robust studies, one at 30 and one at 50. It really will be a question of totality of data. All the data will be included in submission to the FDA for PPD, and we'll have to look at, you know, ultimately what the label looks like in conjunction with the agency. Yeah, just to jump in, Jim. Sorry. We actually do think yes, the dose, the starting dose should be 50 milligrams, what we're, our goal is to offer optionality. You know, obviously, we have to work with the agency and the label, but we wanna offer multiple doses. If in the rare case dose reduction is required, we wanna have that optionality for moms and their treating physicians. Of note, you know, taking medicine in the evening with a meal and getting a good night's sleep is actually a benefit to people living with PPD and depression overall because many of them required sleep aid. We're thrilled with the overall results of the SKYLARK data and the benefit risk that it offers to treat, if approved, moms with PPD. Thank you, Barry, and congrats for the data. Thank you. Our next question comes from Paul Matteis with Stifel. Your line is open. Hey, thanks so much for taking the question. Appreciate it and congrats. Barry, we talked about this briefly, but just to clarify more broadly. From a regulatory perspective, I guess you're gonna be finalizing the MDD submission, and is it clear that these data won't be part of the submission for MDD? I guess, you know, we've seen in the past, right, that at the end of the day, the agency wants all the data that's available on a drug and oftentimes just asks for everything, and that can constitute a major amendment. Just sort of curious if you can give any sort of clarification on your confidence in really splitting the MDD and PPD regulatory processes, given that it's likely gonna be the same division, same reviewer, and have some overlap. Thanks. Yeah. Thanks, Paul, and appreciate the congratulatory note. You know, we do believe the SKYLARK result supports the overall data package for Zuranolone, and we have started the rolling submission of the NDA for MDD. Our plan remains to file the MDD NDA at the H2 of the year. Again, that rolling submission started, followed by a subsequent PPD NDA submission. That's the agreement that we and the agency reached in the fall of last year, really for the most efficient way of filing the package. I'll note that if we're approved in MDD, given the fast-track designation in PPD, it's quite possible that during the DEA review period, that three-month period, that we get an approval for PPD, enabling us to commercialize both MDD and PPD at the same time. It really is about efficiency in filing and, you know, how we present the data to the agency, but that's the plan right now. Our next question comes from Cory Kasimov with JP Morgan. Your line is open. Hi, this is Tiffany on for Cory Kasimov. Congrats on the data and the progress to date. Just a quick question on how what you've learned from ZULRESSO in terms of how it informs the market opportunity for Zuranolone in postpartum and just how you're kind of thinking about the market there as you go forward. Thanks. Thanks, Tiffany. Appreciate the congratulations and the question. Let me turn it over to Chris to talk about the market opportunity. Yeah. Thanks for the question. I'm sure you're aware we've been active in the postpartum market now for approximately three years with ZULRESSO or Brexanolone. Over the course of that time, we've learned a great deal about how to interact with physicians, how to interact with payers and how to interact with moms that are suffering from postpartum depression. There's been significant learning that's come from that opportunity. As you've heard us talk about, we're in a brain health pandemic, including maternal and mental health crisis that's been exacerbated by COVID-19. Postpartum depression has only continued to grow worse over that time period. We know that there are a significant number of moms that are living with postpartum depression. You know, during the course of our conversation this morning, we talked about one in eight moms or approximately half a million women that are suffering with postpartum depression. Only about 28% are actually diagnosed, and fewer than 60% or so are actually treated with therapy. As we've had conversations with clinicians and with payers, what we know is that more is actually needed for these moms. They need rapid and sustained re-resolution of their disease. That we know that by virtue of that engagement with payers and with physicians, that we have a significant opportunity with Zuranolone, if approved, based upon the ability to deliver that rapid and sustained efficacy with a very well-tolerated profile for that medication. We'll continue to leverage learnings from our time with ZULRESSO in the market and offer an oral therapy, an oral short course therapy that will advance care if approved for Zuranolone for those moms that are suffering. Yeah. Thanks, Chris. I guess just to round that out, Tiffany, and it's a great question. You know, we see in the course of commercialization of novel medicines that when something new, easy to access is available, and that we're gonna lean into access here for patients, the numbers grow. I mean, it really is. It's not the right answer for maternal health that only 75,000 women out of the 500,000 are treated. We think with an oral, easy-to-use drug like Zuranolone, those numbers will greatly increase, and our opportunity is to approach that 500,000 moms that have PPD each year. Great. Thank you. Our next question comes from Jay Olson with Oppenheimer. Your line is open. Oh, hey, congrats on these results, and thanks for taking the question. Could you maybe provide some additional color on the unmet needs in the PPD market and maybe help us quantify the magnitude of the commercial opportunity both in the U.S. and outside the U.S. for Zuranolone in PPD? Thank you. Yeah, Jay, you know, thanks for that question. I'll start and turn over to Chris for a little bit more color. As Chris highlighted, epidemiologically, it's estimated that one in eight live births results in a mom suffering from PPD. The opportunity is huge. From a pharmacoeconomic perspective, you know, this presents why to treat both in the U.S. and across the world, the costs are devastating. A mom with PPD not only gets detached from her baby, but can lead to generational impact, costing, you know, hundreds of millions of dollars to the healthcare system over time. It's pretty clear that treating women rapidly, having them attached to their baby helps them, helps their baby, helps the overall family. There's lots of reasons to treat other than just the humanistic view of just getting a mom better. There's economic reasons to treat. Chris, you wanna provide a little bit more? Yeah, sure, Barry. You know, I think taking a step back, I think the message that you heard from us this morning, based on the results of the SKYLARK data, is that there's an opportunity to really change the way that we think about and treat depression, and in particular, postpartum depression. You know, we highlighted that there is profound unmet need in this space that currently there are not therapies that are approved for treating postpartum depression except for ZULRESSO or Brexanolone. By the opportunity to provide Zuranolone to physicians and to the moms that need therapy, we have the ability to provide a therapy that treats these patients with the urgency that they require, not only for themselves, but to continue to provide the care to their babies, you know, as well as to provide support they need to continue to maintain their family relationships. You know, we really see the impact and the opportunity for Zuranolone as being significant by virtue of the profile that it demonstrates, the ability to demonstrate both rapid and sustained efficacy through a short course therapy, as well as the safety profile that we've seen and the tolerability. Again, for that population of moms, the one in eight moms that are experiencing postpartum depression, roughly the half a million women, there's significant opportunity to not only provide them with the treatment that they need, but to continue to increase the opportunity to provide really positive and sustained effects over time. Great. Thank you. Thanks, Jay. Our next question comes from Ritu Baral with Cowen. Your line is open. Good morning, guys. Thanks for taking the question. Congratulations on this top-line data. I wanted to just ask housekeeping question, my usual question. I wanna make sure you guys didn't see any loss of consciousness events within this safety data set. Can you talk to the incidence of either severe sedation events or severe somnolence events, just, you know, given what a focus it was for ZULRESSO in that review cycle? Does timing of assessment of sedation and somnolence figure into the analysis at all? Barry, I know we've had this discussion, you know, dose the night before, assessments were in the morning. Just given the somewhat irregular sleep-wake cycles of the postpartum period, I'm wondering if there are other times of assessments that are of importance to FDA. Thank you. Yeah, Ritu, thanks for the congratulations. Just to emphasize again, we think the benefit risk of Zuranolone for depression here on PPD is very, very clear. You're right, the wake-sleep cycles of moms with PPD, overall with moms and the moms with PPD are quite irregular. We've highlighted that, you know, many moms actually have to use sleep aids, which disturb their ability to wake up when trying to care for babies. We really believe we've got a great package here with Zuranolone. Jim, you wanna take some of the other aspects of Ritu's question? Sure, Barry. Well, Ritu, just to answer the first question up front, we have not seen loss of consciousness in the SKYLARK study or indeed across the entire LANDSCAPE in this program for Zuranolone. Again, very similar to what we've seen in other studies, the vast majority of the somnolence, dizziness, or sedation-related adverse events are mild to moderate. Quite consistent there too. Got it. Is there any differential analysis just on timing of when somnolence and sedation was measured? What I would say there is, we're consistent study to study on when those assessments are made. As you say, next day measures for the primary endpoint. But they're also measured routinely. The other thing that I would say is consistent in this study, we've seen in other studies as well, is that the majority of these adverse events are during the dosing period. Recall that the total duration of the study is out to six weeks. Many of these, not surprisingly, follow the pharmacokinetics of the drug, meaning you see most of these events relatively early, and certainly majority during the treatment period. Got it. I'll get back in the queue. Thank you so much for taking the questions, Jim and Barry. Thanks, Ritu. Our next question comes from Laura Chico with Wedbush Securities. Your line is open. Good morning, and thank you for taking the question. I guess I just had one quick follow-up on the difference between sedation and somnolence. I apologize if I missed that in the prior comments here. Just trying to clarify the distinction in definition. I guess I'll sneak one in too. In terms of pricing, I guess if there's any commentary you can offer here in terms of how you're thinking about pricing. Obviously, the MDD opportunity is substantially larger than PPD, but just curious how we should be thinking about that. Thanks. Yeah. Laura, thanks a lot. I appreciate the question. The adverse events are patients telling physicians what they experienced, and the physician kind of writing it down. There's really not a big difference between somnolence and sedation. Onto your, you know, pricing question. It's too early to talk about pricing per se. What I can tell you is that we're gonna lean heavily to access. Meaning we're gonna do everything we can that if an MDD or PPD patient requires Zuranolone, we're gonna do everything we can to remove barriers to access. That starts with talking to payers on the value-based agreement front and sharing that risk, you know, making sure that they have budget predictability, and aren't fearful of, you know, of allowing that script to go through. We'll do everything we can. You know, we'll get back on more details on pricing as we get closer to approval and understand what the label looks like. Again, we're gonna, you know, do everything we can on the access front. Thanks, Barry. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Morning. Thanks for taking my question. How does this data impact the probability of Zuranolone approval in MDD, or is the division viewing the indications and packages as completely distinct here? Yeah, Salveen, thanks for the question. When we met with the agency in the fall of last year after the positive WATERFALL data, we confirmed a couple things. First, we confirmed that with a positive WATERFALL, we had a viable package for MDD, recognizing that we had two outstanding studies at the time, CORAL and SKYLARK. The agreement with the agency was to move ahead with a rolling submission for MDD, which we've started, include the CORAL data which we reported and had a very positive result, and then an associated NDA filing with the PPD data. Now given the positive SKYLARK data, we're thrilled to, you know, begin that associated NDA. As I've highlighted in the call a little bit earlier, the way the timing we hope works out is should MDD be approved, and we're gonna file that to finish the NDA in the H2 of this year, during the DEA review period, that three-month period, we hope to get the approval given the fast track for PPD and able to launch both indications at about the same time. Now, of course, if one gets approved before the other, we won't wait for approval. We'll start helping MDD patients first if that's the first approval. Thank you. Thanks, Salveen. Our next question comes from Ami Fadia with Needham & Company. Your line is open. Hey, guys, this is Amin for Ami Fadia. Congratulations on the data. I guess I have a two-part question. The first part is about the response rates that you see in day 15, and how does it change as participants. Yeah. Ami, thanks for the question. I'll ask Jim to provide a few highlights here, but what we've seen with the SKYLARK study is, as we've seen across now 3,000 treated patients, a very consistent profile. We see change from baseline at day three, day 15 and outdays to be around the same major change. The data are highly consistent. Now, obviously, we saw a very robust effect relative to placebo. I will note that there were less assessment days, perhaps giving placebo patients less chance for that kind of white coat experience. Really robust results across the board. Jim, you wanna add? Yeah, Barry, I guess what I would add to that is, you know, as we talked about before we had the study results, SKYLARK was really designed to be similar to ROBIN because we had a lot of confidence in the study design in ROBIN, but with a couple of key differences. We've talked about the difference in dosing, so the 50 milligram dose for SKYLARK relative to 30 for the ROBIN study. But we also did have a couple of additional differences in the studies beyond that. One is the size. The SKYLARK study is the largest study that we're aware of that's been run for the treatment of PPD. I would also point to one other change in study design between ROBIN and SKYLARK, where you know we extended the period for women to enter the study. In the ROBIN study it was no more than six months postpartum. In the SKYLARK study that's been extended out to 12 months postpartum. As you can see from the results, which are quite similar to what we had seen from the ROBIN study, that change hasn't made any significant difference. That really is another learning from this study for the treatment of postpartum depression, that we've got a wider window for women who are responding to the drug. Thank you. Our next question comes from Sumant Kulkarni with Canaccord. Your line is open. Good morning. Nice to see the SKYLARK data set, and thanks for taking my question. Just out of curiosity, was there any overlap at all in study participants between SKYLARK and ROBIN? I'm asking this to see if you followed ROBIN participants to see if PPD occurred after birth of another child, and what the duration of effect or episodic retreatment potential of Zuranolone may look like in the PPD patient population. Yes, Sumant, that's a great question. Let me turn it over to Jim. Yep. Good question, Sumant. We actually do not have women who participated in both studies. We do have some, a fraction of women in both studies who are, it is a second or a third experience with PPD, but there are no women who are in both studies. Just a note, Sumant. As we think about commercialization, what happens in the real world, we know given the multiple years experience we have with ZULRESSO, these are anecdotes. We've heard back from moms that after their first childbirth, after being treated, they felt confident to have another child because they, if in fact they suffered from depression again, they were telling us that they knew there was an approach to get them better. We're pretty confident in as we roll out this oral treatment how it might be used in the real world. Got it. Thanks. Thanks, Sumant. Our next question comes from Vikram Purohit with Morgan Stanley. Your line is open. Great. Good morning. Thanks for taking our question. One on baseline characteristics for us. Could you just provide us a bit more detail, or whatever color's available, on baseline characteristics for SKYLARK and how they compare to ROBIN, particularly with regards to what the baseline HAM-D scores were and what portion of patients were on antidepressants coming into the study? Yeah, Vikram. Great question. I guess I'll say that the SKYLARK to us reconfirms what we saw with ROBIN, which was, you know, rapid effects, sustained effects out through day 45 with highly similar profiles. Jim has already highlighted, you know, we use 50 milligrams versus 30 milligrams and have, you know, continued robust effects. Jim, you wanna talk about some of the baseline characteristics that Vikram's asking about? Yeah, absolutely. I think probably the biggest message is similarity across trials. In both studies, entry HAM-D scores, the entry criterion is 26 or above. The mean is gonna be closer to 28 or something like that in the SKYLARK study, so pretty consistent with the ROBIN study. I think that's really what I would say is the key message is by design, the demographics are pretty similar across the two studies. Our next question comes from Yatin Suneja with Guggenheim Securities. Your line is open. Hey, guys. Thank you for taking my questions. Very robust results. Were you able to look at some of the other endpoints? Did you look at patient with anxiety versus without anxiety? I know that's one of the driving factor in a couple of the other studies. Just wondering, you know, what did you see? What about maybe sleep architecture, and any comments there? Yeah. Yatin, thanks for the question. Look, this is, we've reported the top line data here. We look forward in future publications and conference reporting the fertility data. But what we can say in both MDD and PPD now across 3,000 treated patients is a very consistent profile. That's, you know, rapid improvement in depressive symptoms, including improvement in anxiety without impact or negative impact to sleep, which is really what we wanna see in treating depression. As we talked about before, we saw really robust results across MDD. We saw particularly strong results with MDD with elevated anxiety. Very often, PPD presents in moms with that have the darkened mood and the elevated anxiety. Really consistent results across reduction in depressive symptoms, anxiety, without negative impact to sleep. Got it. Thank you. Our next question comes from Marc Goodman with Leerink Partners. Your line is open. Yes, thanks for taking my question. This is Rudy on the line for Marc. So first congrats on the data readout today. I have a question regarding the use of Zuranolone in practice for PPD. It seems like we're going for both monotherapy and add-on to existing antidepressants. Can you remind us what percent of patients are taking background antidepressants in both ROBIN and SKYLARK? Do you expect step add-ons through generic antidepressant even though there's nothing approved for this indication? Yeah, Rudy, thanks for the question. Let me start with this. Other than ZULRESSO, there aren't any drugs specifically approved for PPD. While antidepressants, they're not specifically approved for PPD, as we said on the call, we believe that with both ROBIN and SKYLARK data and the totality of the overall package, including MDD, that Zuranolone should rapidly become the standard of care for women with PPD. It really isn't appropriate to treat them with antidepressants, which can take six-eight weeks to work, if ever. Think about it, a mom detached from her baby, six-eight weeks is an absolute lifetime. That's our goal. As we talked about before, we're gonna lean into access to ensure that scripts that are written are provided. We really don't think it's appropriate medicine to give a mom an antidepressant which takes weeks to work when we have a drug that has shown now repeatedly to work in as little as three days. Our next question comes from Douglas Tsao with H.C. Wainwright. Your line is open. Hi, good morning, and thanks for taking the questions. I'm just curious from a labeling standpoint, what your expectation is in terms of patients who potentially have some persistence of their symptoms. Obviously, the data is quite strong, but presumably there are some patients who do have some continuation of PPD, or even some recurrence, and what your expectation and interactions with the label with the agency might suggest you might be able to achieve. Thank you. Yeah, Doug. Thanks for the question. So, what we have seen in both SKYLARK and ROBIN is a consistent profile. Rapid reduction in depressive symptoms out to day 45. Most of these moms report that the kind of normative state remains for long periods of time, potentially to another depressive episode. Now, we will have data in the Shoreline study on retreatment. While that's not well, that's MDD, it is instructive in terms of what retreatments may need to look like. Most people get better and stay better. In Shoreline, a majority of patients actually require only one two-week dose, and 80% require only one or two two-week doses, so up to four weeks of study. If someone with depression, PPD, has another depressive episode, it could get diagnosed with PPD, it could get diagnosed with MDD, but we believe that, you know, zuranolone will be appropriate in those cases. Okay, great. Thank you so much for congrats on the data. Thanks, Doug. Our next question comes from Gary Nachman with BMO Capital Markets. Your line is open. Hi, thanks for taking our question. This is Evan Huang for Gary Nachman. Congrats on the data. Can you provide some more color on what the initial physician feedback has been on for Skylark data and how they might view that compared to the Robin data? Thanks. Yeah, Evan, great question. Let me ask Chris to start and maybe Jim, 'cause I can tell you that the feedback's been just outstanding. Yeah. I'll give it a start, and then I'll pass it over to Jim, as Barry suggests. First of all, you take a step back, you know, as we're having conversations with physicians about unmet need and postpartum depression, you know, as we've talked about today, there does not exist something in the market that delivers rapid and sustained effects for moms that are suffering from PPD that can be administered through a short course oral therapy. In fact, the only product that's currently approved, as I mentioned earlier, is ZULRESSO for women with postpartum depression. The feedback, based upon the interactions that we've had around ROBIN and SKYLARK, has been highly positive around delivering on what that unmet need actually is for the clinicians that we're communicating with. Again, the rapid and sustained benefits associated with the product, the tolerability profile, the ability to deliver it through a short course oral therapy, that's really important to clinicians that really wanna have the opportunity to treat moms who urgently need therapy. You know, right now what they currently have at their disposal are, you know, SSRIs and other types of established therapies that for a mom that's showing up that needs, you know, effectively that urgent treatment, something that provides potentially relief after four, six, or eight weeks, that's not doing the trick with respect to what it is that they're actually looking for to treat these moms. We believe with the data that we shared through both ROBIN and SKYLARK, we're meeting a highly unmet need in this marketplace. That also translates through to what we're seeing when we engage with payers as well. Payers also recognize that there's high unmet need in this space and that there's an opportunity to treat moms with PPD in a different way than they've been treated to date. Jim, I'll pass it over to you. Yeah. I think Chris said it very well when we talked to docs out there. There's a lot of enthusiasm and honestly a lot of excitement that, as Chris said, there are so many moms who are in urgent need. That's just the situation as it exists today. We talked a little bit about the ADT, the current ADTs are prescribed for postpartum depression, but frankly, the evidence is not great that it provides a ton of benefit. We continue to see some really great results with ZULRESSO Brexanolone, but of course, for a lot of moms, access to Brexanolone has been challenging. The SKYLARK study really reinforces the opportunity with an oral agent with this mechanism of action. That's what the providers are seeing, and I think there's a fair amount of excitement about it. Yeah. Thanks, Chris and Jim. To round that out. What we're also hearing is urgency to diagnose. What we see in depression and medicine in general is when a new tool presents that can help a patient, physicians have a lot more urgency to diagnose. We do believe that with the introduction of Zuranolone, we, in our education, will see the risk assessment tools that are generally available used much more, and the diagnosis rates go up significantly. Got it. Thank you. Our next question comes from Vamil Divan with Mizuho. Your line is open. Great. Thanks for taking the questions, and congrats on the results here. Just one question, and this may be a little bit early, but when you think about labeling, there is some language in the ZULRESSO label around, you know, use in women who are pregnant or during lactation. Looks like, you know, relatively benign information and more based on animal data than anything. But I'm just curious if there's anything else. Would you expect sort of similar language in the label here in, you know, pregnancy and breastfeeding populations or anything sort of different that we should expect, as you think about, you know, how the label might look? Thank you. Yeah. Thanks for the question. Jim, do you wanna take the lactation question? Yeah, absolutely. Vamil, and of course, in the trial itself, we did not exclude breastfeeding mothers. As had been done in earlier trials, participants agreed not to provide breast milk to their infants. We will be looking when we get to the label, as you point out, in the case with Brexanolone, we were actually measuring Brexanolone levels in breast milk, and they're quite low. We'll do the similar thing with Zuranolone. You know, our expectations are that similarly, the levels of Zuranolone in breast milk will be low. That's yet to be provided data. Of course, we'll have to get to specific labeling questions when we get to that point. You know, that's our expectation around the drug itself, that it would behave similarly to the way Brexanolone behaves in breast milk. That's right. Just a good. Let's all keep in mind that we're talking about a two-week course of treatment. Unlike a chronic med, which provides challenges throughout the whole lactation period or breastfeeding period, this is two weeks. Okay. Got it. Thank you. Our next question comes from Neena Bitritto-Garg with Citi. Your line is open. Hey, guys. Thanks for taking my question. I just wanna go back to some of the questions earlier around the rate of somnolence and sedation. I'm just curious if in your regulatory discussions, either around Brexanolone or around Zuranolone, if there was maybe a cap that FDA talked about in terms of the rate of those sorts of adverse events. You know, even cross-comparing the data here to Brexanolone, it seems like you have seen higher rates of somnolence and sedation than historically. Thanks. Thanks, Neena, for the question. Let me emphasize that the rates of somnolence and sedation here are actually not that high when you compare it to the labels of antidepressants that are out there. Everyone should take a look. They're used, they're safe, but I think the adverse event tables are not remembered. The second key point here, these are mild to moderate adverse events, and when you look at the discontinuation rate due to adverse events on the trial, it's extremely low. In the overall benefit risk, the key is that any adverse event doesn't negatively impact the patient to stopping drug or in this case, dropping off a trial. We see dropout rates being extremely low. We're highly confident in the benefit risk here and the opportunity to help moms with PPD. Got it. Thank you. Thanks, Neena. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open. Good morning. Thank you for taking my question and my congrats on the data results as well. I'm curious, maybe your latest mechanistic hypothesis on why you're seeing this work in both MDD and PPD, but seeing a larger effect size in the latter. I guess along those lines, I know a full breakdown of HAM-D subcomponents. We'll wait for the detailed data. But I guess broadly speaking, I'm curious if you're seeing a mix of HAM-D component effects that looks similar to what you see in MDD, but just maybe more robust across the board, or if there are particular elements and subcomponents of HAM-D where it seems like PPD patients preferentially benefit. Thanks. Thanks, Brian. Let me just emphasize again that we are seeing consistency of data in both PPD and MDD across 3,000 treated patients. When you look at change from the baseline at day three, 15, 28, out to day 45 or 42 in the MDD case. The drug kinda does what the drug does. It reduces depressive symptoms, anxiety without disruptions to sleep in all of our studies. It's really been consistent. I think the really important question on why and mechanism is critically important. I'm gonna ask Jim to explain it because that's a critical point of why we're seeing such robust results with Zuranolone. Absolutely. I'd say the core hypothesis that we've had consistently is that what we think is happening is that in depression you've got overactivity in key brain circuits, and that's not our work. There's a lot of work looking at four brain circuits that are overactive in depression. What both Brexanolone and ZULRESSO are hypothesized to be doing is calming down that overactivity. As we think about it, the difference between populations may well be what triggers that change in brain function. In postpartum depression, of course, it's the changes in physiology associated with parturition and birth, where it's gonna be more variable in MDD. Once that imbalance has been triggered, it's been triggered. That's why we think that the drugs are treating both patient populations. The only difference is really in the triggering. Our next question comes from Tim Lugo with William Blair. Your line is open. Thanks for the question and congratulations on the results. Most of them have been asked, but I don't think I heard if there were any instances of suicidal ideation at the less than 5% rate. Obviously, I know that's an important you know event given the class and the history of the class. Yeah, Tim, great question. We don't, but Jim, you wanna comment more about what's going on here and why we don't? Yeah, I think that's the short answer, Barry, is you look at. Of course, we do track suicidality, and we see no evidence for suicidality or suicidal ideation. We also routinely track for withdrawal. With the physician's withdrawal checklist, don't see any signs of withdrawal in the study, either. Great to hear. Tim, what's important, and thanks for the question, is this working a fundamentally different way. You know, offering a new mechanism of action and innovation, which we haven't seen in over 35 years, is really exciting. Thanks for the question. Our next question comes from Danielle Brill with Raymond James. Your line is open. Hi, guys. Good morning. Congrats on the data, and thanks so much for the question. First, just to follow up to an earlier question, can you remind us how long post-treatment that breastfeeding restrictions would apply? And then also just curious what the baseline in HAM-D 17 scores were in the treatment and placebo arm. Thanks. Well, thanks, Danielle. Jim, you wanna take those? When it comes to breastfeeding, this is again in the trial. They basically agreed to not breastfeed until seven days after the last dose of zuranolone. The second question? Oh, just curious of the baseline HAM-D scores from the two arms. Right. The baseline HAM-D scores were approximately 28 for each arm. Yeah. Very, very well balanced. Thanks, Danielle. Our next question comes from Ritu Baral with Cowen. Your line is open. Hi, guys. Thanks for taking the follow-up. Very quick one, given time. Barry, are you committed to having a different brand for PPD for Zuranolone? Or is this something that is still on the table? I know this feeds a little bit into pricing considerations, but also, you know, potential sales force and sales force strategy. Can you speak to that at all? Yeah. Ritu, great question. Look, we and Biogen are still in discussions about the way to commercialize. You know, Zuranolone is a drug both for MDD and PPD, so it's highly likely that it'll be the same brand and the same overall pricing strategy. What's important to us is, you know, people living with MDD and PPD get access to this drug, which is why we're partnering with payers to remove all barriers. You know, launching a new depression drug and seeing innovation in this space really for an oral drug for the first time in over 30 years is really exciting. Thanks, Ritu, for the follow-up. Thanks. Thank you. There are no further questions. I'd like to turn the call back over to Barry Greene for any closing remarks. Thanks everyone for joining us this morning. We believe that completion of the SKYLARK study is yet another important step towards our goal of bringing Zuranolone to the market to help those suffering from MDD and PPD. As you've heard in today's call, these data meaningfully contribute to demonstrating Zuranolone's potential to meet the needs of people with depression, including those diagnosed with PPD. I hope in our voices and our comments, you can hear how thrilled we were with these data. We remain committed to making a difference in the lives of people living with brain health disorders, so they can thrive and get back to normal, healthy, independent life. Zuranolone, as well as the rest of our pipeline, is incredibly exciting, and we continue to build ourselves to be leaders in brain health and an opportunity to be a top-tier pharmaceutical company. That's where we're going. Thanks everyone, and have a great day. Goodbye. This concludes today's conference call. You may now disconnect.