Title

Presentation

Sage Therapeutics, Inc. misses on earnings expectations. Reported EPS is $-1.01 EPS, expectations were $-0.99.

Operator: Good afternoon. Welcome to Sage Therapeutics First Quarter 2025 Financial Results Conference Call. [Operator Instructions] 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 expressed written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Ashley Kaplowitz, Vice President of Investor Relations and Capital Markets at Sage.

Ashley Kaplowitz: Good afternoon and thank you for joining Sage Therapeutics’ first quarter 2025 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 and slides related to today’s call. 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 first quarter 2025.

Our Chief Operating Officer, Chris Benecchi, will provide an update on the ongoing commercialization of ZURZUVAE and key financial results from the first quarter 2025. Our Chief Scientific Officer and Interim Head of R&D, Mike Quirk, will then provide a brief update on our pipeline. With that, I’ll now turn the call over to Barry.

Barry Greene: Thanks, Ashley and thank you everyone for joining us this afternoon. We had a strong start to 2025 as we advanced our commercialization efforts for ZURZUVAE, the first and only oral treatment approved for adults with postpartum depression, or PPD, and we also are strategically progressing our refocused pipeline. Now before I get into detail, I wanted to briefly address an important initiative. The Sage Board of Directors continues to advance its strategic alternatives process. As we previously noted, Sage is conducting a comprehensive process to evaluate a broad range of opportunities for the company to maximize value for shareholders. The review process remains ongoing. We’ve not set a timetable for the review process and do not intend to disclose further developments until we determine that disclosure is appropriate or necessary.

Now turning back to ZURZUVAE, we continue to be energized by the profound impact we’re having on women with PPD and are driving our efforts forward to bring ZURZUVAE to more women suffering from this urgent medical condition. In the first quarter of 2025, ZURZUVAE was shipped to greater than 3,000 women with PPD. That represents a 22% increase from the fourth quarter of 2024. We generated $13.8 million in collaboration revenue for ZURZUVAE in the first quarter, which represents 50% of the net revenue recorded by Biogen, a 21% increase from the fourth quarter of 2024. Importantly, we are starting to see signs of a system-wide paradigm shift in the way health care providers, specifically OB/GYNs, are increasingly screening, diagnosing and treating PPD.

We believe that enhanced screening, diagnosis and treatment, paired with the continued elevated national dialogue around maternal mental health are critical to accelerating ZURZUVAE growth in PPD. In fact, as of today, I’m pleased to share that we’ve reached a significant milestone in advancing patient care. Since launch, we’ve shipped ZURZUVAE to greater than 10,000 women with PPD. We remain focused on our goal of establishing ZURZUVAE as the standard of care for women with PPD. And with our continued progress, we believe we’re making advancements toward that goal. In addition to executing on our launch, we also continue to make progress on our pipeline. Last year, we recalibrated our R&D approach, and we significantly reduced our cost structure, aligning our resources around the areas that we believe have the greatest potential for value creation.

As a result of this work, we prioritized our clinical pipeline in neuropsychiatry and neurodevelopmental disorders, where we see a strong scientific rationale and believe a significant unmet need exists. Specifically, we’re excited about the potential opportunities for both SAGE-319 and our NMDA receptor NAM platform, which we believe could add significant value for shareholders and patients if our development efforts are successful. We also continue to evaluate next steps for SAGE-324. Mike will provide additional details on these programs. As we previously shared, Mike was appointed Interim Head of R&D and is leading the team forward. I’m confident in the continuity and execution of our clinical priorities under his leadership. With the commercial momentum of ZURZUVAE in PPD, our focused R&D approach and cash runway expected to support operations to mid-2027 we believe we are well-positioned toward our goal of creating value for our shareholders.

I’ll now turn the call over to Chris to discuss ZURZUVAE and our financial performance for the quarter. Chris?

Chris Benecchi: Thanks, Barry. I’ll begin with an update on our ZURZUVAE commercialization progress, ongoing initiatives to maximize reach to women with PPD and conclude with our financials for the first quarter of 2025. As Barry noted, we are off to a strong start this year as demand for ZURZUVAE in the treatment of women with PPD continued to grow. In the first quarter of 2025, we shipped greater than 3,000 prescriptions, representing a 22% increase from the fourth quarter of 2024. We continue to see greater than 70% of women prescribed ZURZUVAE receive it as their first new treatment for PPD, which we believe shows the potential for ZURZUVAE to become the standard of care for this urgent medical condition. In terms of prescriber trends, in the first quarter, almost 80% of prescriptions came from OB/GYNs who are at the forefront of peripartum care, the most critical time to screen, diagnose and treat PPD.

In addition to OB/GYNs, we saw the balance of prescriptions come from a mix of psychiatrists and PCPs. As we’ve expanded our promotional efforts, including through the recent sales force expansions, we believe that utilization of ZURZUVAE will continue to increase among these physician types. Further, we continue to see strong overall prescribing trends with ongoing broader adoption of ZURZUVAE. Total ZURZUVAE writers increased by greater than 20% in Q1, and we continue to observe that once in HCP writes, there is strong repeat prescribing. Importantly, we are seeing that once an OB/GYN has prescribed ZURZUVAE, there is a significant increase in the number of women with PPD they treat based on prescriptions for all medications. At the beginning of the year, we announced a robust investment plan intended to help accelerate the launch of ZURZUVAE, which included a joint sales force expansion to broaden our reach of health care providers who treat PPD, investments in media opportunities to further communicate the ZURZUVAE brand value proposition and amplify the message that PPD is an urgent medical condition, and increased visibility via social media to support PPD awareness and educational efforts.

In the first quarter, we made significant progress in these areas. Our recent sales force expansion is now complete with our initial expansion in the fourth quarter of 2024, followed by additions in the first quarter. Following our launch of consumer social media at the end of 2024, we saw greater than 65 million video views across Meta and TikTok. And at the beginning of April, we launched our first HCP social media campaign, which deepens our engagement with HCPs and advances efforts to build awareness of ZURZUVAE in PPD. We are pleased with the progress made to date and anticipate that our investments this year will help support our goal of significant top line revenue growth in 2025. We look forward to sharing additional updates in the coming quarters.

Now turning to our financial results for the first quarter of 2025. As a reminder, our full financial results for this period are detailed in our press release issued this afternoon with further details in our 10-Q. We reported collaboration revenue from the sale of ZURZUVAE of $13.8 million in the first quarter, a 21% increase compared to the fourth quarter of 2024. As a reminder, our reported collaboration revenue is 50% of the net revenue Biogen reports for ZURZUVAE. R&D expenses were $22.8 million and SG&A expenses were $57.6 million in the first quarter of 2025. Sage underwent a reorganization late last year designed to right-size the company to support the ongoing launch of ZURZUVAE and our focused pipeline development efforts. R&D expenses were significantly reduced as a result of the restructuring.

You’ll see that reflected in the decrease of our R&D expenses by 68% in Q1 2025 as compared to the same period in 2024. Further, last quarter, we said we expected the first full quarter of savings from the reorganization to be realized in Q1 2025. An example of those cost savings is the nearly 40% decrease in R&D expenses in Q1 2025 as compared to Q4 2024. As we noted previously, while we expect ZURZUVAE joint commercialization investment to increase in 2025, we anticipate overall operating expenses will substantially decrease in 2025 relative to 2024. We continue to be very diligent with our investments aimed at creating shareholder value. Our net loss for the first quarter of 2025 was $62.2 million as compared to our net loss for the fourth quarter of 2024, which was $95.8 million, illustrating Sage’s continued efforts to streamline business operations.

Based upon our current operating plan, we anticipate that our existing cash, cash equivalents and marketable securities of $424 million as of March 31, 2025, together with anticipated funding from ongoing collaborations and estimated revenues and excluding any potential milestone payments we may receive under our collaboration agreements will support our operations to mid-2027. With that, I’ll turn the call over to Mike to provide an update on our pipeline. Mike?

Mike Quirk: Thanks, Chris. As Barry noted earlier, we remain focused on developing medicines for neuropsychiatry and neurodevelopmental disorders, where we see a strong scientific rationale and believe an unmet need exists. I’ll begin with SAGE-319, our wholly-owned extrasynaptic preferring GABA A receptor positive allosteric modulator, or PAM, which was designed to have novel pharmacology and a differentiated profile from other GABA A receptor PAMs in our portfolio. Our goal with SAGE-319 is to demonstrate meaningful clinical effect and a product profile that is differentiated by a broader therapeutic index given the preferential modulation of extrasynaptic GABA A receptors. SAGE-319 is currently being investigated as a potential treatment for behavioral symptoms associated with certain neurodevelopmental disorders, which could include autism spectrum disorder, Tourette’s and other rare neurological disorders, all of which are known to have high burdens on patients, families and the health care system.

We expect to share data from the Phase 1 Multiple Ascending Dose or MAD study by late 2025 and anticipate that the upcoming results from this study could enable potential studies in a patient population in early 2026. Further, we have two orally administered NMDA receptor negative allosteric modulators or NAMs in preclinical development, SAGE-817 and SAGE-039. Our intention with these drug candidates is to develop a drug with similar or better efficacy than NMDA receptor blockers like ketamine, but with a potentially improved safety and tolerability profile. SAGE-817 and SAGE-039 have distinct preclinical profiles with SAGE-817 inhibiting a broad array of NMDA receptor subtypes and showing stronger inhibition, whereas SAGE-039 exhibits subtype specificity and has more limited inhibition.

We are also exploring SAGE-324, our wholly-owned GABA A receptor PAM for various potential indications, including seizures and developmental and epileptic encephalopathies or DEEs. We expect to provide an update on next steps, if any, in mid-2025. To be clear, we are not spending developmental dollars on SAGE-324, but rather, we are evaluating SAGE-324 as part of an overall portfolio decision. We remain excited about opportunities to bring forward developmental candidates from our deep reservoir of proprietary compounds that target the GABA and NMDA receptor systems. While many of these activities are ongoing in the background, we look forward to sharing updates on our progress with you in due course. With that, I will turn it over to Ashley to help facilitate the Q&A portion of today’s conference call.

Ashley?

Ashley Kaplowitz: Thanks Mike. As a reminder, we will now be answering questions related to the strategic alternatives process and ask that questions be focused on our first quarter 2025 results. [Operator Instructions] Now I’ll turn the call over to the operator to handle Q&A. Operator?

Operator: Thank you. [Operator Instructions] We will take our first question from Anupam Rama with JPMorgan.

Malcolm Kuno: Hi, thanks for taking the questions. This is actually Malcolm Kuno on for Anupam. What kind of early pull-through are you seeing from your sales force initiatives?

Barry Greene: Hey, Malcolm. Yes, I’ll start and I’ll ask Chris to comment. As you saw, we had a really strong first quarter of the year, with over 20% growth both in demand and revenue. As a reminder, both companies expanded the sales force in the first quarter. That is complete. And what we believe is that we’ll continue to see quarter-on-quarter revenue growth throughout the remainder of the year.

Chris Benecchi: Yes. What I would add is when we made the decision strategically to expand the sales organization first in the fourth quarter of last year and again, beginning this year, what we wanted to do is we wanted to broaden our reach and increase the frequency associated with the contacts that we were having with health care professionals. And the implications of that have been that OB/GYNs have really seen a significant portion of our activity. And in fact, with 80% of prescriptions coming from OB/GYNs, we really are doing a lot of work to make sure that there is an activated prescriber base on the front line of peripartum care who are engaged and prepared to not only prescribe ZURZUVAE but to, in effect, broaden the screening process and the diagnosis of PPD, which is really exciting.

It’s always important to have that kind of foundation. So, we’ve really focused in the sales force on OB/GYNs and really capitalizing on that as an opportunity as we go forward.

Malcolm Kuno: Great. Thank you.

Chris Benecchi: Thanks, Malcolm.

Operator: We will take our next question from Salveen Richter with Goldman Sachs.

Shrunatra Mishra: Hi, this is Shrunatra on for Salveen. Could you provide some additional color on the pipeline and your upcoming catalysts? And particularly, what is driving Sage’s confidence in the GABA and NMDA pathways, given the setbacks on the pipeline that we saw last year?

Barry Greene: Yes. Thanks for the question. I’ll start, and then I’ll ask Mike to comment. So, as we talked about earlier in the year, we recalibrated our R&D approach and really focused our pipeline. We believe that we are now pursuing drugs with the pharmacology appropriate for indications we’re pursuing that SAGE-319. We’re also focused with our NMDA NAMs on very validated targets. So, we feel very good about the drugs that we have, the pharmacology that we have and the indications that we’re going after. We believe that if successful, we’ll create major shareholder value as well, of course, patient impact. Mike, do you want to talk a little bit more about that?

Mike Quirk: Yes Barry, if I could just add on to a little bit of that. I mean, I think there are two elements of our recalibrate approach. One is the areas of disease biology that we’re focused on and really prioritizing neuropsychiatry and neurodevelopment disorders where we think there is a very strong biological rationale for both SAGE-319 or extrasynaptic preferring GABA A positive allosteric modulator as well as for our NMDA receptor NAM platform. And second, by also looking at those indications where we think that there are feasible regulatory pathways. And across both of these programs, 319 and the NMDA NAM platform, as Barry mentioned, one of the key elements that we’re looking at is making sure that we leverage clinical insights and clinical validations as much as possible.

So, for example, with the NMDA receptor NAMs, we know that negative modulation or inhibition of NMDA receptors is a very valid target in areas of neuropsychiatry and neurodevelopment disorders with molecules such as ketamine and memantine. The key difference is with our NAMs, we believe that we’ll be able to provide similar or better therapeutic efficacy as open channel blockers, but with an improved tolerability profile. So again, really leaning into the clinical insights that we can derive across our programs. And similarly, with 319 being a differentiated extrasynaptic preferring PAM, we’re able to leverage a lot of our own learnings as well as learnings from others in being able to have a lot of the efficacy signals that we’ve seen in various indications, but also potentially have an improved tolerability profile by specifically modulating the extrasynaptic components of the GABA system.

Shrunatra Mishra: Thanks Mike.

Operator: Thank you. We will take our next question from Vikram Purohit with Morgan Stanley.

Morgan Gryga: Hi. This is Morgan on for Vikram. Thanks for taking our question. So, on ZURZUVAE, for those prescribers and patients deciding not to use ZURZUVAE as their first-line treatment, what do you believe are the key factors as to why? And which efforts do you have underway that you think are likely to be key to addressing these reasons? And then second question, could you speak about the concentrations of the sales force in particular regions? I know in the last update, you had said in the regions where the sales force had been expanded, you had seen, I believe it was a 33% uplift. Could you provide any color or details there on updates and how that’s panning out? Thank you.

Barry Greene: Yes, Morgan, thanks for the questions. So let me answer the second one first. As we said, both companies have completed their expansion in the first quarter. With that expansion complete, we believe that we’re going to see quarter-to-quarter growth in the foreseeable future. So that’s really all we can comment about on the sales force. As Chris said earlier, our reach is greater to more OB/GYNs. And in this quarter, we saw a significant number of new writers, and we continue to bring new writers on every quarter. And as you heard from Chris earlier, those new writers become repeat writers as new writers come on. So that’s a trend we’re seeing. In terms of ZURZUVAE, more than 70% of women prescribed ZURZUVAE are receiving it as their first new treatment for PPD. So, about a year into launch, that’s quite a remarkable number. We really don’t see obstacles to ZURZUVAE becoming the frontline use.

Morgan Gryga: Okay. Thank you.

Operator: Thank you. We will take our next question from Ritu Baral with TD Cowen.

Unidentified Analyst: Hi, guys. This is Athena on for Ritu Baral. Thanks for taking the question. During the last earnings call, you guys noted that inventory levels for ZURZUVAE were kind of fluid. So how should we look at these levels now and when can we expect them to stabilize? Thank you.

Barry Greene: Thanks, Athena. Let me ask Chris to talk about the inventory.

Chris Benecchi: Yes. So, what I can say is that inventory varies from quarter-to-quarter as wholesalers apply their various purchasing habits associated with inventory. So, it’s tough to peg inventory as it fluctuates up and down. What’s most important is to really look at demand here and demand is measured by shipments from specialty pharmacies directly to women with PPD, which is why we are so encouraged by the more than 3,000 shipments that went through in the first quarter of 2025 as reflective of the uptake of the interest in ZURZUVAE and the uptake of the medication early in the launch. So again, I would direct you to focusing on the demand rather than the inventory fluctuations over a period.

Barry Greene: Alright. Thanks, Chris. Thanks, Athena.

Unidentified Analyst: Thank you.

Operator: Thank you. We will take our next question from Paul Matteis with Stifel.

Unidentified Analyst: Hey, this is Julian on for Paul. Thanks so much for taking my questions. I know first quarter tends to be a little bit difficult to understand read-through on to the rest of the year. But I guess in thinking about what you guys are seeing in demand so far for 2Q, I guess, are you expecting sort of a reacceleration in growth? And I guess were you surprised by the somewhat flat quarter-over-quarter shipments you saw from 4Q? Thanks.

Barry Greene: Yes, Julian, thanks for the question. Well, we actually didn’t see a flat quarter-to-quarter. We saw an over 20% growth from the fourth quarter to the first quarter in both demand and revenue. So, we are excited by that. And I can’t really comment on how the second quarter has started other to say what we said before, which is and we said this in January, we see quarter-to-quarter growth throughout each quarter of this year. I am pretty confident in that statement.

Operator: Thank you. We will take our next question from Ami Fadia with Needham.

Ami Fadia: Hi. Good afternoon. Thanks for taking my question. Just a quick follow-up to the previous question, as we think about the expansion in the commercial efforts by both yourself and Biogen, how should we think about kind of the acceleration in growth in these sort of shipments as the quarters progress? Maybe if you could sort of help us sort of get some sort of a sizing of by how much you have expanded the efforts? And what type of impact you expect from that, that would be helpful. And then a quick follow-up on the inventory question, can you just quantify if there was any inventory changes in the quarter that might have impacted the end market revenue? Thank you.

Barry Greene: Thanks for the question. I will talk about the first part and ask Chris if there is anything to comment on inventory. So, look, as we said, the sales force expansions were complete in the first quarter. We are excited and encouraged to see over 20% growth in the first quarter in both revenues and demand. And I can’t quantify it, and we are not giving forward-looking forecast, but we can say that we see quarter-on-quarter growth. And as I commented previously, we are getting new writers every quarter, and that is a strategic focus. And as you have heard Chris say many times, those new writers become repeat writers. So, you think about that dynamic as well as system-wide dynamic, continuing to grow PPD. Again, we believe that ZURZUVAE is the key to unlock the blockbuster potential in PPD, and we believe we are on a trajectory to make that happen. Chris, any inventory comments?

Chris Benecchi: Yes. I think in terms of inventory, I think I have said it, and I will repeat the statement. I think there is fluctuation in terms of buying patterns associated with the wholesalers here. And as you see a therapy like ZURZUVAE that continues to grow quarter-over-quarter, your wholesalers are trying to project what inventory is going to look like. And when you add expansion into the mix, they are also trying to figure out how to really project forward what the inventory should look like. So, there is going to be fluctuations in terms of inventory as they try to project forward what the uptake of ZURZUVAE is going to look like as we go forward. So, I wouldn’t point you to any one thing in the specific first quarter around inventory other than to go back and say the truest predictor of the success of the product is looking at the demand trend that we are on, as Barry noted, 22% quarter-over-quarter, more than 3,000 women with PPD received ZURZUVAE.

Barry Greene: Yes. Thanks Chris. Thanks Ami.

Ami Fadia: Thank you.

Operator: Thank you. We will take our next question from Brian Abrahams with RBC Capital Markets.

Brian Abrahams: Hi. Thanks so much for taking my question. What do you guys sense is the overall awareness of ZURZUVAE, both amongst OB/GYNs and amongst the expecting a new mother community. And I guess I am also curious what kind of metrics you can use to assess both that awareness as well as the degree to which screening for PPD may be increasing? Thanks.

Barry Greene: Yes. Thanks. Let me ask Chris to start, and I can loop back with some additional color.

Chris Benecchi: Yes. So, it’s a great question, Brian. What I would say is – and we do tracking studies on a routine basis quarter-over-quarter. And so, we look at what physician awareness is of ZURZUVAE. And what we have said is that there is approximately a 90% aided awareness for ZURZUVAE, which given where we are at the launch is remarkably high. So, when you go out and you look at the physicians that are out there that are treating with PPD, when you have the conversation with them around the medication, 90% with aided awareness know ZURZUVAE and understand what it’s being used for. So, again, I think that that’s really remarkable at this stage. We are going to continue to do everything that we have talked about around personal promotion through the sales force as well as non-personal promotion to broaden reach, increase our frequency, not only with OB/GYNs, but also with psychiatrists and PCPs who see women with PPD to further expand that, again, capitalizing on the understanding of the product and to broaden the impact that it has when a physician wants to choose ZURZUVAE for women with PPD.

I would also say that we have seen a real uptick in terms of screening and diagnosis amongst those who have actually chosen to prescribe ZURZUVAE. So, think about it like this. Once a physician has the experience with ZURZUVAE, he or she begins to change her prescribing practices, not only because of the interest in the medication, but an increased or a renewed interest in screening and diagnosis. So, there is not just an opportunity here in effect for ZURZUVAE to be used, but it’s to increase the overall size of the population that’s viable for a medication like ZURZUVAE.

Barry Greene: Thanks Chris. Thanks Brian.

Brian Abrahams: Thanks Chris. Thanks Barry.

Operator: And we will take our next question from David Amsellem with Piper Sandler.

David Amsellem: Thanks. So, I wanted to ask you about your partner, and specifically, has anything changed regarding their commitment to the product? And I guess to the extent that things are status quo strategically, just looking at ZURZUVAE as primarily a women’s health product and where the rest of Biogen’s business is, do you get the sense that their commitment to the product might wane just given the strategic fit or lack of strategic fit, just wanted to get your thoughts there. Thank you.

Barry Greene: Yes. Thanks David and welcome to the team. So, what I can say is there is no change to the way we are working with our Biogen counterparts. And I would say they, like us, are very excited by the impact, the profound impact we are having on PPD and the paradigm shift we are seeing in the market. So, I mean you would have to ask them, but what we are seeing so far is highly encouraging in terms of a build a market opportunity.

David Amsellem: Okay. Thank you.

Barry Greene: Thanks David.

Operator: Thank you. We will take our next question from Douglas Tsao with H.C. Wainwright.

Douglas Tsao: Hi. Good afternoon. Can you hear me?

Barry Greene: Yes, Doug, we can hear you.

Douglas Tsao: So, I think as you mentioned that once a prescriber writes a script [ph] of ZURZUVAE, you just see greater activity for PPD in that office. Are they – and I think you might have said and I am sorry if I misheard that they might be writing other products as well. So, I am just curious sort of how you are seeing that mix and ultimately what it takes to shift them just so they can immediately go for ZURZUVAE?

Barry Greene: Yes. Doug, thanks. I will take that. So, just to clarify what we have said is once a healthcare provider, in our case, mainly OB/GYNs writes ZURZUVAE, we are seeing a significant number of new PPD or PPD they are seeing in their practice. So, you see a huge practice growth in terms of the women they are treating with PPD. We also said that more than 70% of the women prescribed ZURZUVAE are receiving it as their first new treatment for PPD. So, that trend is a very strong trend. And I said this earlier, there aren’t really obstacles getting in the way of frontline use. You might have a mom already on an antidepressant where ZURZUVAE is added. So, that wouldn’t be part of the 70%. But we are not seeing reluctance to use ZURZUVAE first.

Douglas Tsao: Okay. And Barry, that’s really helpful. And then I guess, I am just curious, if you see any, and obviously, you did grow quarter-on-quarter. I am just curious if you saw any seasonal impact. Obviously, across the industry, we typically see resets and so forth. And so, I am just curious if as we think about the future quarters that we should see sort of some catch-up in terms of the growth.

Barry Greene: So, again, we completed the sales force expansion in the first quarter. There is some disruption when you do that, we still had strong quarter-to-quarter growth. And it’s too early to know whether there is any kind of seasonality associated with ZURZUVAE and PPD. We don’t have the classic first quarter Medicare issues that some drugs have. This is commercial and Medicaid. So, we wouldn’t see that. Thanks Doug.

Douglas Tsao: Thank you very much.

Operator: Thank you. We will take our next question from Uy Ear with Mizuho.

Uy Ear: Hey guys. Thanks for taking our question. Just curious, could you speak a bit about gross to net, whether you have seen it improve from the fourth quarter, or does it – or in this quarter, did it experience a typical gross to net depression that other products in the space experience? Thanks.

Barry Greene: Yes. Chris, do you want to take that?

Chris Benecchi: Yes. We haven’t communicated exactly what the gross to net is in terms of the percentage. What we have said, though, is that when you think about the gross to net for ZURZUVAE, which is the first oral therapy approved for the treatment of women with PPD that it doesn’t require the same type of gross to net that you might see with other antidepressants used more broadly in this category because I think payers recognize the novel or the uniqueness of this medication, which is really important. So, we haven’t communicated the number. It’s not that substantial gross to net that we have talked about. And I think, Barry, as you said it, given that there isn’t fluctuations associated with Medicare and things like that, that you wouldn’t expect to see the ups and downs associated with gross to net in the category like this with the medication like ZURZUVAE.

Barry Greene: Thanks Chris. Thanks Uy for the question.

Operator: Thank you. We will take our next question from Joel Beatty with Baird.

Joel Beatty: Thanks. In the survey we published earlier this month, we received comments from quite a few docs that said they liked the profile of ZURZUVAE and wanted to prescribe it more. But then they said that getting payer coverage was often challenging and that this had been a barrier to their use. I am curious, how does that fit with what you are hearing from OB/GYNs regarding challenging payer coverage?

Barry Greene: Yes. Joel, I think we hear a lot about these surveys, and I would challenge you to find out those you are surveying whether they are actually using the drug or not or whether they are making assumptions. We see a lot of surveys come back with historical biases, which are not true. You have heard us, we have got over 95% coverage. So, the coverage is very, very strong. Now, sometimes we hear about a challenge with a prior auth or specialty pharma. But the majority of moms are getting – a vast majority of moms are getting ZURZUVAE in less than a week from prescription and many, many receive ZURZUVAE in two days to three days. So, we are not hearing issues with coverage at all.

Chris Benecchi: I would add, Barry, 70% of women prescribed ZURZUVAE are receiving it as their first new treatment for PPD, which again is another proof point to the kind of coverage that we have and the ability of a woman with PPD to get it and to get it without onerous prior authorizations and step edits.

Barry Greene: Yes. This launch profile is very different than “classic” branded launches. And unfortunately, what we see is we see many healthcare providers answering questions with a historical bias rather than a current a fact base.

Joel Beatty: Thank you.

Barry Greene: Thanks Joel.

Operator: Thank you. We will take our next question from Laura Chico with Wedbush Securities.

Laura Chico: Hi. Good afternoon. Thanks very much for fitting me in here. I guess one question I just wanted to clarify. I know there were about 3,000 shipments in the quarter that occurred. Have you quantified the number of HCPs you have that are actively prescribing? And I am just trying to understand what would be a reasonable or aspirational goal in terms of the number of prescribers. Thanks.

Barry Greene: Yes. Thanks Laura for the question. Let me ask Chris to comment.

Chris Benecchi: Yes. So, Laura, we have looked at the number. We have a sense for the size of the population here in terms of OB/GYNs and psychiatrists and PCPs, but we haven’t communicated the number at this time. What we have talked about is the number of shipments that go out. We have talked about the percentage of prescriptions coming from OB/GYNs and other physicians, so not from us yet on the exact number of physicians.

Barry Greene: What I would add, Laura, and it’s an astute question is, again, we continue to see new writers coming on every quarter. We don’t see that stopping. Once we bring new writers on, they become repeat writers. Obviously, the new writers from last quarter are repeat writers. And more and more offices come on where they are using ZURZUVAE more than 7% frontline and continuing to repeat. So, the reason we are confident in our quarter-to-quarter growth is that the dynamics are in place to continue to make that happen.

Laura Chico: Okay. That’s helpful, Barry. And maybe I will just toss one, I will talk kind of related, but I don’t know if you will be able to answer this. In terms of the average scripts per provider, how are you – would you be able to quantify kind of the changes you are seeing there? I think your qualitative commentary suggests it’s increasing, but wondering if you can add any metrics there. Thank you.

Barry Greene: I can’t quantify it. We are really not providing that. We are saying that once someone writes, we see a significant number of new patients they are treating in the practice. And again, if ZURZUVAE is used more than 70% frontline, we are getting most of that use. There are dynamics where someone might be an antidepressant or previous antidepressant, but that 70% continues to grow. And once we raise awareness is an office, they don’t look back. They want to treat postpartum depression.

Laura Chico: Thanks very much.

Barry Greene: Thanks Laura. Appreciate it.

Operator: Thank you. Your next question comes from Marc Goodman with Leerink Partners.

Basma Radwan: Hi. Good afternoon. This is Basma on for Marc. Can you please tell us what is the current penetration in the OB/GYN, and what is your target? And we also have a second question on the pipeline. Regarding the 319 and the DEEs, are you basing the decision to advance the development in the DEEs based on the safety profile? And if so, what is the threshold of somnolence rates to make a go or no-go decision for the development? That’s it for us. Thank you.

Barry Greene: So, let me start with the second one. I think if you are talking about DEEs, we are talking about SAGE-324. And there is a number of factors we are looking into. It’s not about – it’s about whether doses that are suitable for chronic administration will work in the DEE population. It’s also about what the regulatory pathway looks like and our portfolio. So, once we have clarity around dose, regulatory pathway, portfolio, we will guide mid this year the path forward, if any, with 324. I am not sure we can say much more about your first question. So, I think we have already talked about that.

Basma Radwan: Prefect. Thank you.

Operator: Thank you. Your next question comes from Sumant Kulkarni with Canaccord.

Sumant Kulkarni: Good afternoon. Thanks for taking my question. It’s nice to see the growth on ZURZUVAE, but what specifically needs to happen to get a more meaningful inflection on the product, so we could see sales far outstrip the SG&A dollars that are spent currently? And how would you put that in context relative to your current cash runway or versus the timelines on any meaningful pipeline catalysts that might help extend that runway?

Barry Greene: Sumant, thanks for the multi-factorial question there. So, look, we are excited by the fact that we had greater than 20% growth in the first quarter from fourth quarter in both demand and revenue. As we have said, we continue to see quarter-to-quarter growth now that the expanded force is in there, and we have got an aligned commercialization plan. We don’t see that growth slowing. We have also said that ZURZUVAE as a brand will be cash flow positive exiting 2026. We are pretty confident in that. As we see opportunities to expand or spend more to continue to grow ZURZUVAE, we will take advantage of those opportunities. In terms of product pipeline progression and overall profile of the company, we have guided that we have got cash runway into 2027. And what goes on further will depend upon data and our decisions to move other drugs forward.

Sumant Kulkarni: Thank you.

Barry Greene: Thanks Sumant.

Operator: Thank you. Your next question comes from Joon Lee with Truist Securities.

Asim Rana: Good afternoon. This is Asim Rana on for Joon. Congrats on the quarter and thanks for taking the questions. Just a question on 324, I mean what remaining work are you looking to do on 324 to develop for DEE? And then in terms of ZURZUVAE, what’s the persistence of prescribers? Do you see any prescribers that start the drug and then stop prescribing? Thank you.

Barry Greene: Let me take the second one. I guess in terms of ZURZUVAE, as we have said, once a healthcare provider writes ZURZUVAE, they become a repeat writer. We are seeing that consistently. I can’t really comment on those that have written and stopped. We are not seeing that dynamic in the marketplace. It’s quite the opposite. In terms of 324, as we said earlier on the call, we are looking at dose appropriate for chronic administration in DEEs, regulatory pathway and our overall portfolio. And once we have clarity on all of those, which we will have midyear, we will provide some guidance on paths forward, if any. Just another point is we are not spending developmental dollars on SAGE-324. It’s really people working on answering the questions that I have outlined.

Asim Rana: Thank you.

Barry Greene: Thank you.

Operator: Thank you. This will conclude the Q&A portion of today’s call. With that, I will turn it back over to Mr. Greene for closing remarks.

Barry Greene: Thanks Rachel and thanks again to everyone for joining us this afternoon to review our results from the first quarter of 2025. As we look ahead to the ongoing commercialization of ZURZUVAE and advancements in our focused pipeline, I am confident that we are making important progress on our mission to deliver life-changing brain health medicines, so every person can thrive. Thanks again everyone and have a great evening. Bye.

Operator: This does conclude today’s call. Thank you for your participation. You may now disconnect.