Sage Therapeutics, Inc.

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.

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 Green, our Chief Executive Officer, who will provide an overview of our progress during the first quarter 2025. Our Chief Operating Officer, Chris Benucki, will provide an update on the ongoing commercialization of Zerzuve 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.

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 Zerzuve, the first and only oral treatment approved for adults with postpartum depression, or PPD. And we also are strategically progressing our refocus 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 Zerzuve, we continue to be energized by the profound impact we're having on women with TPD and are driving our efforts forward to bring Zerzuve to more women suffering from this urgent medical condition. In the first quarter of 2025, Zerzuve was shipped to greater than 3,000 women with TPD. That represents a 22% increase from the fourth quarter of 2024. We generated $13.8 million in collaboration revenue for Zerzuva 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 healthcare providers, specifically OBGYNs, are increasingly screening, diagnosing, and treating PPD. We believe that enhanced screening, diagnosis, and treatment paired with a continued elevated national dialogue around maternal mental health, are critical to accelerating Zerzuve 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 Zerzuve to greater than 10,000 women with PPD. We remain focused on our goal of establishing Zerzuve as a 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 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 Zerzuva and 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 Zerzuve and our financial performance for the quarter. Chris?

Thanks, Barry. I'll begin with an update on our Zerzuve 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 Zerzuve and the treatment of women with PPD continue 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 Zirzuve receive it as their first new treatment for PPD, which we believe shows the potential for Zirzuve 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 OBGYNs, who are at the forefront of peripartum care, the most critical time to screen, diagnose, and treat PPD. In addition to OBGYNs, 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 Salesforce expansions, we believe that utilization of Zerzuve will continue to increase among these physician types. Further, we continue to see strong overall prescribing trends with ongoing broader adoption of Zerzuve. Total Zerzuve writers increased by greater than 20% in Q1, and we continue to observe that once an HCP writes, there is strong repeat prescribing. Importantly, we are seeing that once an OB-GYN has prescribed Zirzuve, 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 Zirzuve, which included a joint Salesforce expansion to broaden our reach of healthcare providers who treat PPD, investments in media opportunities to further communicate the Zerzuve 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 Salesforce 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 Zerzuve and 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 10Q. We reported collaboration revenue from the sale of Zerzuve 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 Zerzuve. 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 Zerzuve 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 Zerzuva 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?

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 SAGE319, 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 SAGE319 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. SAGE319 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 healthcare system. We expect to share data from the Phase I 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, SAGE817 and SAGE039. 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. SAGE817 and SAGE039 have distinct preclinical profiles, with SAGE817 inhibiting a broad array of NMDA receptor subtypes and showing stronger inhibition, whereas SAGE039 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 in 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 phage 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?

Thanks, Mike. As a reminder, we will not be answering questions related to the strategic alternatives process and ask that questions be focused on our first quarter 2025 results. Please limit yourself to one question. If you have an additional question, feel free to return to the queue. Now I'll turn the call over to the operator to handle Q&A. Operator?

Thank you. If you would like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, please press star 1 to ask a question. We will pause for just a moment to allow everyone an opportunity to signal for questions.

We will take our first question from Anupam Rama with JP Morgan.

Hi, thanks for taking the question. This is actually Malcolm Kuno on for Anupam. What kind of early pull through are you seeing from your Salesforce initiatives?

Hey, Malcolm. Yeah, 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.

Yeah, 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 healthcare professionals. And the implications of that have been that OBGYNs have really seen a significant portion of our activity. And in fact, with 80% of prescriptions coming from OBGYNs, 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 their Zubay, 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 OBGYNs and really capitalizing on that as an opportunity as we go forward.

Great. Thank you.

Thanks, Malcolm. We will take our next question from Saldine Richter with Goldman Sachs.

Hi, this is Srinath Rao 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?

Yeah, thanks for the question. I'll start, and then I'll ask Mike to comment. You know, 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 stays through 1-9. We're also focused with our NMD 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 go after. We believe that if successful, we'll create major shareholder value as well, of course, patient impact. Mike, you want to talk a little bit more about that?

Yeah, Bear, 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. We think there is a very strong biological rationale for both SAVES-319 or exosynaptic 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 differences 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 and 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 extra synaptic components of the GABA system.

Thanks, Mike. Thanks, Renata.

Thank you.

We will take our next question from Vikram Pirahit with Morgan Stanley.

Hi, this is Morgan on for Vikram. Thanks for taking our question. So on Zirzuve, for those prescribers and patients deciding not to use Zirzuve 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 details there on updates and how that's panning out? Thank you.

Yeah, Morgan, thanks for the question. So let me answer the second one first. As we said, both companies have completed their expansion the first quarter. With that expansion complete, we believe that we're going to see a quarter-to-quarter growth in the foreseeable future. So that's really all we can comment about on the Salesforce. As Chris said earlier, our reach is greater to more OBGYNs. 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 Zirzuva, more than 70% of women prescribed Zirzuva 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 Zirzuva becoming the frontline use.

Okay, thank you.

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

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

Thanks, Athena. Let me ask Chris to talk about the inventory. Yeah.

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're 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 Zirzuve 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.

Right. Thanks, Chris. Thanks, Athena.

Thank you. Thank you.

And we'll take our next question from Paul Matisse with Stifo.

Hey, this is Julian. I'm Paul. Thanks so much for taking my question.

I know first quarter, you know, tends to be a little bit difficult to understand, you know, read through onto the rest of the year. But I guess in thinking about, you know, what you guys are seeing in demand, you know, so far for 2Q, you know, I guess, are you expecting sort of a reacceleration in growth? And I guess, were you surprised by, you know, the somewhat, you know, flat quarter over quarter payments you saw from 4Q? Thanks. Thanks.

Yeah, Julian, thanks for the question. Well, we actually didn't see a flat quarter-to-quarter. We saw over 20% growth from the fourth quarter to the first quarter in both demand and revenue. So we're 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 this year.

I'm pretty confident in that statement.

Thank you.

We'll take our next question from Ami Sadio with Needham.

Hi, Gaurav. Thanks for taking my question. Just a quick follow-up to the previous question. As we think about the expansion and the commercial efforts by both yourself and Biogen, how should we think about 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've 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.

Thanks for the question. I'll talk about the first part and ask Chris if there's anything to comment on inventory. So, look, as we said, the Salesforce 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're not giving forward-looking forecasts, but we can say that we see quarter-on-quarter growth. And as we've commented previously, we're getting new riders every quarter, and that is a strategic focus. And as you've heard Chris say many times, those new riders become repeat riders. So you think about that dynamic as well as system-wide dynamic, the team to grow PPD. Again, we believe that Zerzuve is the key to unlock the blockbuster potential in PPD, and we believe we're on a trajectory to make that happen.

Chris, any inventory comments? Yeah, I think in terms of inventory, I think I said it and I'll repeat the statement. I think there's fluctuation in terms of buying patterns associated with the wholesalers here. And as you see a therapy like Zerzuve 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're also trying to figure out how to really project forward what the inventory should look like. There's going to be fluctuations in terms of inventory as they try to project forward what the uptake of Zerzuve 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're on. And as Barry noted, 22% quarter over quarter, more than 3,000 women with PPD receive Zerzuve.

Yeah, thanks, Chris. Thanks, Ami.

Thank you.

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

Thanks so much for taking my question. What do you guys sense is the overall awareness of Zerzuve, both amongst OB-GYNs and amongst the expecting a new mother community? And I guess I'm 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.

Yeah, thanks. Let me ask Chris to start, and I can loop back with some additional color.

Yeah, 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 Zerzuve, and what we've said is that there is approximately a 90% aided awareness for Zerzuve, 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 knows their Zuvia and understand what it's being used for. So, again, I think that that's really remarkable at this stage. We're going to continue to do everything that we've talked about around personal promotion through the sales force, as well as non-personal promotion to broaden reach, increase our frequency, not only with OBGYNs, 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 Zirzuve for a woman with PPD. I would also say that we've seen a real uptick in terms of screening and diagnosis amongst those who've actually chosen to prescribe Zirzuve. So think about it like this. Once a physician has the experience with Zirzuve, 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's not just an opportunity here, in effect, for Zirzube to be used, but it's to increase the overall size of the population that's viable for a medication like Zirzube.

Thanks, Chris. Thanks, Brian. Thanks, Chris. Thanks, Barry.

And we'll take our next question from David Amselin with Piper Sandler.

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 Zerzube 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.

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

Thank you. Thanks, David.

Thank you. Thank you. We will take our next question from Douglas Sao with H.C. Wainwright.

Hi, good afternoon. Can you hear me?

Yep, Doug, we can hear you.

Okay. So I think because you mentioned that once a prescriber writes a script reserve, you just see greater activity for PPD in that office. You know, are they, and I think you might have said, and I'm sorry if I'm deferred, but they might be writing other products as well. So I'm just curious sort of how you're seeing that mix and ultimately what it takes to shift them to sort of immediately go first with that.

Yeah, Doug, thanks. I'll take that. So just to clarify what we've said is once a healthcare provider, in our case mainly, you know, OBGYNs, writes Zirzuve, we're seeing a significant number of new PPD or PPD they're seeing in their practice. So you see a huge practice growth in terms of the women they're treating with PPD. We also said that more than 70% of the women prescribed Zirzuve are receiving it as their first new treatment for PPD. So that trend is a very strong trend. 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 Zirzuva is added, so that wouldn't be part of the 70%, but we're not seeing reluctance to use Zirzuva first.

Okay. That's really helpful. And then I guess I'm just curious, and obviously you did grow quarter on quarter, I'm just I'm curious if you saw any seasonal impact, you know, obviously across the industry, typically being, you know, resets and so forth. And so, you know, I'm just curious if, you know, as we think about the future quarters, if we could sort of touch up in terms of the growth.

So, you know, again, we completed the Salesforce expansion in the first quarter. You know, there's some disruption when you do that. We still had strong quarter-to-quarter growth. And it's too early to know whether there's any kind of seasonality associated with Zuzuvay and PPD. You know, we don't have the classic first quarter Medicare issues that some drugs have. This is commercial Medicaid, so we wouldn't see that.

Thanks, Doug. Okay, great. Thank you very much.

Thank you. We will take our next question from Ayer with Mizuho.

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

Yeah. Chris, you want to take that?

Yeah. We haven't communicated exactly what the gross-to-net is, you know, in terms of the percentage. What we've said, though, is that when you think about the gross-to-net for Zerzuve, 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've talked about. And, you know, 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 a category like this with a medication like Sursuvay.

Thanks, Chris. Thanks for the question.

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

Thanks. In the survey we published earlier this month, we received comments from quite a few docs that said they liked the profile of Zerzuvae 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'm curious, how does that fit with what you're hearing from OBGYNs regarding challenging payer coverage?

Yeah, Joel, I think we hear a lot about these surveys, and I would challenge you to find out those you're surveying, whether they're actually using the drug or not, or whether they're making assumptions. We see a lot of surveys come back with historical biases which are not true. You've heard us, we've 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, you know, the majority of moms are getting, a vast majority of moms are getting Zirzuva in less than a week from prescription, and many, many receive Zirzuva in two to three days. So we are not hearing issues with coverage at all.

I would add, Barry, 70% of women prescribed Zirzuva are receiving it as their first new treatment for PPD, which, again, is another proof point for the kind of coverage that we have and the ability of a woman with PPD to get it and to get it without owner's prior authorization to step in.

This launch profile is very different than quote-unquote classic branded launches, and unfortunately what we see is we see many healthcare providers answering questions with a historical bias rather than a current-day fact base.

Thank you. Thanks, Joel.

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

Hey, 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'm just trying to understand what would be a reasonable or aspirational goal in terms of the number of prescribers. Thanks.

Yeah, thanks, Laura, for the question. Let me ask... Chris, to comment?

Yeah. So, Laura, we've looked at the number. We have a sense for the size of the population here, you know, in terms of OBGYNs and psychiatrists and PCPs, but we haven't communicated the number at this time. What we've talked about is the number of shipments that go out. We've talked about the percentage of prescriptions coming from OBGYNs and other physicians. So, not from us yet on the exact number of physicians.

Exactly. What I would add, Laura, and, you know, it's an astute question, is, again, we continue to see New riders coming on every quarter, we don't see that stopping. Once we bring new riders on, they become repeat riders. Obviously, the new riders from last quarter are repeat riders. And more and more offices come on where they're using more than 70% front line and continuing to repeat. So the reason we're confident in our quarter-to-quarter growth is the dynamics are in place to continue to make that happen.

Okay, that's helpful, Barry. Maybe I'll just toss one. I'll talk kind of related, but I don't know if you'll be able to answer this. In terms of the average script per provider, would you be able to quantify kind of the changes you're seeing there? I think your qualitative commentary suggests it's increasing, but wondering if you can add any metrics there. Thank you.

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

They want to treat postpartum depressions.

Thanks very much.

Thanks, Laura. I appreciate it.

Thank you. Your next question comes from Mark Goodman with Learing Partners.

Hi, good afternoon. This is Basmon for Mark. Can you please tell us what is the current penetration in the OBGYN 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 of the DEEs based on the safety profile? And if so, what is the threshold of some of the rates to make a go or no-go decision for the development? That's it for us. Thank you.

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

Got it. Thank you.

Thank you.

Thank you.

Our next question comes from Sumant Kulkarni with Canaccord.

Good afternoon. Thanks for taking my question. It's nice to see the growth on Zue, 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?

Suman, thanks for the multifactorial question there. So, look, we're 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've said, we continue to see quarter-to-quarter growth now that the expanded force is in there and we've got an aligned commercialization plan. We don't see that growth slowing. We've also said that Zerzuve as a brand will be cash flow positive exiting 2026. We're pretty confident in that. As we see opportunities to expand or spend more to continue to grow Zerzuve, we'll take advantage of those opportunities. In terms of product pipeline progression, overall profile of the company, we've guided that we've got cash runway into 2027 and What goes on further will depend upon data and our decisions to move other drugs forward. Thank you.

Thanks, Suman.

Thank you. Your next question comes from Jun Li with Truist Securities.

Good afternoon.

This is Asim Rana on for June. 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 good luck for DEE? And then in terms of Zerzuve, what's the persistence of prescribers? Do you see any prescribers that start the drug and then stop prescribing? Thank you.

Let me take the second one. I guess in terms of Zerzuve, as we've said, once a healthcare provider writes Zerzuve, they become a repeat writer. We're seeing that Can't really comment on those that have written and stopped. We're not seeing that dynamic in the marketplace. It's quite the opposite. You know, in terms of 324, as we said earlier on the call, we're looking at dose appropriate for chronic administration DEs, regulatory pathway, and our overall portfolio. And once we have clarity on all of those, which we'll have mid-year, we'll provide some guidance and some paths forward, if any. Just another point is we're not spending developmental dollars on sage seeds. It's really people working on answering the questions that I've outlined.

Thank you. Thank you.

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

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 Zerzuve and advancements in our focus pipeline, I'm confident that we're 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.

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