Morning, everyone. Welcome to our Piper Sandle Healthcare Conference. Excited to kick off day two of our conference. Really thrilled to have Sage Therapeutics here. Barry, thank you for being here with us. Yeah, yes, thanks for having us and appreciate Piper for organizing this. Oh, we love having you at our conference, and it's been a pleasure covering your name. Lots to talk about over the next 25 minutes. I think a great place to start off would be to talk about the reprioritization and really focus on commercial execution of Zurzuvae. Maybe just give us some color around, I think, in third quarter, you reported $11 million. It was up 49% quarter over quarter. Just how do you see what were the drivers of growth, and what are you doing to continue? What are the key objectives to continue growing this? Right. I'll get to Zurzuvae in a minute because that clearly is a very important value driver for Sage. But before I do, I think it's important to understand that Sage is still a leading thinker in brain health. The unmet need is enormous. We have a significant library of neuroactive steroids, including oxysteroid chemistries, that we can still target dysregulated circuits in the brain for a variety of diseases. And we'll be talking a lot more about that in the months to come. Certainly, Zurzuvae is a key value driver, as you mentioned. And just for background, Zurzuvae was approved last year for the treatment of women with postpartum depression. It's an oral medication that women take at night. It shows improvement in postpartum depression as little as three days. And we're actually hearing that in the real world, too. And it's a 14-day oral short course therapy. So it really is a kind of a revolution in postpartum depression. As I said before, I think Zurzuvae is the key to unlock the blockbuster potential in postpartum depression because for the first time ever, the healthcare providers in the front line, mostly OB-GYN, have the right tool in their toolbox to treat women with postpartum depression. As you mentioned, we had a very strong third quarter. We had a 49% quarter-on-quarter growth in revenue, hitting over $22 million in revenue. That represents just over 2,000 prescriptions shipped in a quarter. So we're really helping many women. That's more than 4,000 women we've helped since launch, which is very gratifying. And the reports we're hearing from the field are what we saw in clinical trials, that Zurzuvae works quickly. We've heard statements like, "The burden has been lifted from my shoulders as early as day three." You can imagine the reports we get out of the field with lots of tears associated with it because of the tremendous impact that we're having on mom, baby, and family. So it's very strong. The key drivers have been what we suspected in the beginning, which is that the OB-GYNs are owning postpartum depression. And that makes sense. If you think about the patient journey, a woman consults with OB-GYN before getting pregnant, works with OB-GYN through pregnancy, obviously at birth. And if she's had a prior history of mental distress or depression, the risks are higher. And OB-GYNs are the right people to do that. The paradigm shift we're seeing is that before Zurzuvae, the OB-GYNs might suspect depression and refer to a psychiatrist or to primary care. The paradigm shift we're seeing in ACOG, the Congress is really helping us drive this, is that they're being asked to screen, diagnose, and treat. And if you think about the roughly six-week course of visit that a mom will be under the care of an OB-GYN, if a mom is reporting darkened mood, anxiety, inability to sleep at two weeks, they're through that baby blues period and into postpartum depression. And if the OB-GYN picks it up before the four or six-week visit, mom might be well already. And if she's not, they can refer out at that point as well. But fortunately, we're hearing for the most part the effects of Zurzuvae, again, as we've seen in the clinical trials. Okay. Now, as many of you know, I have a two-and-a-quarter-year-old son. Exactly. And that's exactly what the experience is, that as soon as you go back after having given birth, you have that week follow-up with your OB-GYN. And even at the hospital, they screen you for it. So there's definitely pretty much the first 12 weeks as you have your OB-GYN appointments, you do get asked that question. So that is a new initiative. So I guess the question that investors will have is, with your sales force as well as the expansion that is incorporated, how many OB-GYNs have been called on? What's the bucket that you guys are moving forward? Because I agree with you, it is a driver of growth, and having that Zurzuvae in that toolbox is going to be key. Yeah, it's really important that you've just had this experience where you were asked the questions at every step of the way. Let me make a couple of comments about diagnosis. Then let's talk about epidemiology, and then we can go to OB-GYN. So while many people, you know, you live in New York, so New York's very good at it, Massachusetts is very good at it, and the states are getting better and better at implementing mandatory screening. But here's what we have to further change. Two years ago, if you asked an OB-GYN about depression, you'd hear, "We don't know. Think about it. We don't look for it. It's not our thing." Starting with the launch of Zurzuvae and ACOG's guidance to screen diagnose, many OB-GYNs will say, "Well, if a mom is hysterical at the two-week visit, I suspect something." If you ask them further, "What if she's not connected with baby or agitated or not sleeping or isn't breastfeeding properly?" "Well, that's not PPD." "Well, in fact, it could be." So we've got a lot of work to do to still help people understand the journey that moms are on and how to look for the signs and symptoms of postpartum depression. I'd say we're kind of good right now, but we have an opportunity to be outstanding. And if you think about epidemiology, and this may be changing, but right now, approximately one in eight live births epidemiologically results in a postpartum depression episode. So if I go to an office and they've delivered 800 babies last quarter and only diagnosed 20 moms, in theory, they're missing 80 potential moms. So there's really opportunity with the sales force and others to continue to do disease state awareness, help understand the signs and symptoms of postpartum depression, and even implement some practice changes. And we're starting to see that. You mentioned this. There are many practices that won't bring moms back in two weeks but do a phone call. Many of them are starting to bring them back, not necessarily for the OB-GYN, but a PA or an NP. And it works out from a business model perspective, but it certainly works out from a mom's health perspective. So of that approximately 500,000 live births a year, that's our opportunity. Now, you know, through a mental health crisis, through COVID, there are a lot more prior incidences now. So we may see that epidemiology changing. We're hearing in some places in the United States, it's more like one in seven, one in six. We don't yet have the data to fully declare the epidemiology changing. The opportunity is pretty significant. We've got to move that 500,000 where about 100,000 are getting treated to most moms getting treated. That really has to happen at the OB-GYN level. Now, we are calling on a significant number of OB-GYNs with our field force. When we started the launch in January, we were split more OB-GYN and psych. Clearly, uncertainty whether OB-GYNs would pick us up. We're moving more and more to focus on OB-GYNs because last quarter, over 70% of the scripts, in fact, came from OB-GYN. And we talked about this before. When you think about the patient journey, that's where we want to pick up Postpartum Depression. How many OB-GYNs are there in a target population? Or how many OB-GYNs with centers where they deliver a large number? We haven't. Target focus, yeah. We haven't. We and Bai just haven't talked specific numbers, but what I can tell you is that we increased the sales force starting this quarter, and in very short order, we're seeing a dramatic increase in the impact that the field force is having as measured by new docs being seen in new scripts. And what's really gratifying is the dynamic that we're seeing is once an OB-GYN starts using Zurzuvae, their practice is seeing many, many more moms with PPD. Now, obviously, they were seeing it before, so it's really a change in diagnosis. And we know that from the codes that once Zurzuvae is prescribed, that practice group is seeing multiple more of moms. And that Zurzuvae, when used, is primarily being used frontline. In less than a year of launch, we're already seeing that dynamic change where OB-GYNs are owning the disease and prescribing Zurzuvae for the most part frontline. And when you think about since the launch, how big was the sales team and how big is the sort of expansion? And do you think you have the sufficient group, or do you consider maybe even expanding it beyond the current status? Yeah, that's really important. So when we launched Zurzuvae, we said we're thinking really big about the opportunity of PPD. We think, again, PPD has blockbuster potential. But we started with clear focus because we wanted to make sure that what we suspected would happen, OB-GYNs would write and own the disease, did happen. Now that we're seeing that, we were able to expand. We'll continue to expand investment with success. So, for example, we increased our non-personal promotion already this year. We increased our sales force this year. I'm confident that we and Biogen will have an aligned 2025 investment plan that is multiples greater than the 2024 investment plan. And if there's opportunities for both of us to further expand, we'll do that, capturing more of the OB-GYN, psych, and primary care audience. Okay. Could you maybe talk to us, based on the 4,000 women that have already taken Zurzuvae, at what time point do they like it post giving birth? How is it after a week that they take it? What does your data tell you on sort of at what point post-birth? Yeah, so at a macro level, the majority of prescriptions are written before the six-month mark. I see. As you talked about, it's mostly under the care of OB-GYN. We've had reports that when moms come in for their two-week visit, if they're diagnosed with postpartum depression, they might get Zurzuvae two to four days later, delivered directly to their home, and at their four-week visit or six-week visit, they're reporting symptom relief, so it does vary, but the important part is that for the most part, PPD is being picked up in the first six months, which is really, really important because, as you're well aware, the longer a mom goes undertreated, untreated or undertreated, she's at risk, that baby's at risk, and it has dire consequences to the family unit and health economic consequences to our society. Do you foresee now that the year is coming to an end and we're heading into the beginning of the year, are you expecting to give guidance and projections how you're thinking about revenue numbers for 2025 for Zurzuvae? How do you envision that? I don't think that we'll be in the position to give specific guidance. And remember, we're partnered here, so we have to make sure that we and our partners are fully aligned on what we're saying. But we do see continued growth, and we'll talk about what kind of growth we'll see. We saw, again, we saw over 40% growth in shipments from second to third quarter. Given the holiday season in December and some of the other dynamics, I'm not expecting that level of growth. But we're continuing to see more and more scripts. And as I said, once a healthcare provider writes Zurzuvae, they're writing multiple times. In fact, the vast majority of those that wrote July or before have already written two or three more times since then. So we're seeing the dynamic of repeat writers as well. What we'll continue to do on a quarter basis is provide the metrics of shipments, revenues, and then some of the other dynamics we're seeing out there, such as coverage, which was very, very good to date. And that leads into, I think, coverage. You guys noted you're at 90%, right, which is pretty amazing within one year of launch. Should we envision that getting it to 100% is pretty easy now or probably less heavy lifting there? That's question one. And question two, it's like, what is the process by which once a physician notes they need to be on Zurzuvae, what is the process and how long does it take till they get the product in their hands? Right. So, as you mentioned, from a commercial and a government pay perspective, and from a government pay, this is mostly Medicaid, about 50% of births per year, about 50% are Medicaid births. Less than that are prescribed, but that's about the ratio. So the really good news is that all three of the major PBMs have favorable coverage for Zurzuvae, which is very rare, as you know, in the first year of a branded launch. All the major insurers have favorable coverage for Zurzuvae. So that last 10% are some of the smaller plans, which we'll get to. And for the most part, the favorable coverage I'm talking about is no steps and a very kind of checkbox prior auth, doctor's attestation rather than tests and assessments. We do have a very liberal free goods program. The free goods right now are a combination for truly functionally uninsured and those that the system's just taking too much time to work out, so they get the drug. We don't want moms to wait. We do believe that into next year, that free goods program will move mostly to the functionally uninsured. So there'll always be some number of, whether it's 10% or 20%, there'll always be some number of functionally uninsured. The way the process works, and this is new for OB-GYN offices, is through a specialty pharma. So if a mom comes in either telephonically or into the office and is diagnosed with postpartum depression, the healthcare provider electronically fills out the script, and depending on the insurance company, fills out the prior auth and any other information required. Now, what's important is since the medication is delivered to the home, the home address has to be right, and then the patient is contacted to verify that, yes, she wants the drug and then contacted that the home address is right, and someone will be available. It's a scheduled drug, so someone has to be available to receive drug when delivered. When it works really, really well, moms can get drug in two-to-three days. Wow. If there's a glitch in the system, the address isn't quite right, zip code's transposed, or the. Just formality mistake. The pharma can't get in touch with the mom, they're not home, or they won't be home that day. It can take five to ten days. The majority are within a week. Okay. That's very, very helpful. How do you think about sort of now with the additional sales force being really ready to go, you're seeing physicians who have experience with the product or uptaking it, are we going to see, I guess, a big change in 1Q, 2Q? Are we going to just sort of see all the hard work that's being put in sort of like a cadence of the launch of a ramp from 1Q to 2Q, 3Q? How should we think about sort of the growth over a quarter over quarter? I can't give you a magnitude of growth. Yeah, no, but that's trend. But what we should be seeing throughout the course of next year and the year after is continued quarter to quarter growth. Obviously, with inventory levels, and 22 is a nice number, but still on the relatively small number. And the number of specialty pharmas, we might see kind of the inventories up and down. But what I'm really looking for is that steady shipment growth, quarter to quarter shipment growth. And we should see that through the course of next year. Okay. And I think we always get also, now that, how has your partner been in terms of really ensuring and aligning with you to make sure that Zurzuvae's resources are really, that you have every tool possible and their commitment? Have you seen a change with your partner in terms of what they're willing to bring to the table to help you through this process? Yeah, Biogen's been a very strong partner all along. What I can say is that at the field level, it's seamless interactions. Yeah. Obviously, we've had a number of people out there for years, Zulresso, and a lot of experience in postpartum depression. So as new people have come on, both our people and Biogen's people, the more experienced field folks have really been willing to help and guide people through the system, which is great. And then at the kind of headquarters level, our marketing teams work step by step. And Biogen's done additional work like bringing toxicology online so that if a mom isn't fortunate enough to get diagnosed in the first couple of weeks over OB-GYN, and sometimes symptoms don't really manifest till the third or fourth month, you've got toxicology out there as a resource. As I said, I believe that going into 2025, we'll have a very aligned investment plan, including some potential kind of direct-to-consumer work that is the new kind of direct-to-consumer where you can go DirecTV or right to someone's device rather than big ads on cable news networks, so it's a very well-aligned force. Last quarter, I think you heard from Bai Jin that they continue to be pleasantly surprised by the growth and the excitement surrounding postpartum depression, and it is a shining light for both companies. I mean, being in the maternal mental health space is something everybody wants to see us succeed in. And then, I guess what investors are struggling with is trying to foresee what is the full market opportunity, right, for Zurzuvae? Is this a peak $300 million drug, $500 million drug, a billion-dollar drug? And I think at the seat that you guys are sitting, and now that you've been launched for a year and you're seeing the uptake, what are the metrics or factors that point that this is more in the direction of a billion-dollar drug or more versus just peak sales of, I don't know, $200 million? Again, let's look at the numbers. Yeah. If we think about 500,000 moms, 500,000 a year having postpartum depression, it's enormous. Now, there's no such thing as 100% market share. But if we can get a significant percentage of only those moms treated today, we've got blockbuster potential. If we can change the diagnosis rates, which we're starting to do, and change the diagnosis to prescription of Zurzuvae frontline, you've got potential over that, so, again, can't give a specific number, but we clearly see a very significant opportunity, and as we've said, we believe that Zurzuvae as a brand has an opportunity to be positive cash flow into 2026. That should give investors a view of where we think it's going without naming specific numbers. Okay. Very helpful. I would love to get your thoughts around the outlook for, in your view, in 2025 across the pipeline. I think it's clear for investors the commitment that you guys are bringing to Zurzuvae to make it a commercial success. But how do you envision sort of the pipeline growth and opportunities for investors to want to own ahead of those pipeline data readouts? Yeah, absolutely. So, look, as I said upfront, we have a significant knowledge base of creating neuroactive steroids, including oxysteroid chemistries that are brain penetrant. And as everybody knows, one of the key challenges with brain health is getting the drugs into the brain. So we do that very well. We've got a vast knowledge of different diseases and the malfunctioning of circuitry, if you will, and then we can use our chemistries to target that dysfunction. We have been very successful with our GABA PAMs in postpartum depression and, frankly, been less successful in some other indications as well as our NMDA positive allosteric modulators. But we can learn from all that and apply it to the pipeline. The first best example of that learning is SAGE-319. So SAGE-319, which is in phase one today, and we will have data next year. I'll talk a lot more about what that is in January. We'll have data next year. It's been designed to be extra-synaptic preferring. Unlike the balanced PAMs, which are what Zurzuvae is, which work very, very well, the idea behind the extra-synaptic preferring SAGE-319 is that it has slightly different pharmacology. If we got it right, a larger therapeutic index because we're targeting the extra-synaptic area. What that should translate to is being able to give better dosing without some of the somnolence and sedation we see today. If that holds out next year, there's a variety of places like neurodevelopmental diseases we can turn to. We also have a platform of NMDA negative allosteric modulators. So think kind of ketamine, again, without some of the side effects we see from ketamine. We'll talk more about this, but we're pretty confident that we can apply the learnings from success and lack of success to the earlier stage pipeline and be a Zurzuvae company, but a Zurzuvae company with an emerging pipeline as well. I think it's clear that there's a lot of learnings from developing new generation molecules with the platform that allows you then to be positioned. Looking back into 2024, are there learnings from clinical execution that could help? Because sometimes, could there be elements of execution in terms of type of studies, type of patients that you've learned from that could also be incorporated for sort of ensuring the clinical success of the next generation compound? Absolutely. I'm glad you mentioned that, so what I already talked about is learnings from the pharmacologic design of a molecule, so we've taken those learnings and we're taking that and designing molecules to hit brain circuits in slightly different ways, and we think applying that learning, but absolutely, as we think about the conduct of studies, a challenge in any brain health or CNS study is often that the endpoints are more subjective, and when you have subjective endpoints, you have large placebo effects, so study conduct, site selection, how to minimize placebo effects, how to make a patient population more homogeneous, all of those learnings we're going to apply going forward, and clearly, there's learnings in what we did in 2022, 2023, and 2024. Okay. Perfect. And what is the current cash runway? So fund not only the commercialization, but also the development or creation of the pipeline? What we said previously is we've got cash runway well into 2026 and that we will revise that shortly. Okay. Perfect. Barry, it's been a pleasure having you. Thank you. Very much looking forward to 2025. So let's say thanks, Barry, for a great discussion. Thank you.