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spk22: Good morning and welcome to Sage Therapeutics first quarter 2024 financial results conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media Selection section of Sage's website at sagerx.com. This call is the property of Sage Therapeutics and recording, reproduction, or transmission of this call without the express written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Ashley Kaplowitz, Vice President of Investor Relations and Capital Markets at Sage.
spk10: Good morning, and thank you for joining Sage Therapeutics' first quarter 2024 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 marks by Barry Green, our Chief Executive Officer, who will provide an overview of our progress during the first quarter of 2024. Our Chief Business Officer, Chris Bonecki, will provide an update on the ongoing commercialization of Zerzube. We will also be joined by Laura Gault, our Chief Medical Officer, who will review development activities across our programs. We will then be joined by Kimi Noguchi, our Chief Financial Officer, who will review our financial results from the first quarter of 2024. Mike Quirk, our Chief Scientific Officer, will be available for questions during the Q&A portion of the call. With that, I'll now turn the call over to Barry.
spk06: Thanks, Ashley, and thank you, everyone, for joining us this morning. As we progress through 2024, we are singularly focused on addressing unmet needs in brain health. And while the science is extremely challenging, we remain motivated toward a common goal, improving human health. As you may have seen, last week we announced negative results from our precedent study in the DALS and MDAR program in participants with mild cognitive impairment related to Parkinson's disease. We're deeply disappointed for patients and their families. As we know, mild cognitive impairment in Parkinson's disease can have a devastating impact on an individual's life. We continue to believe that these results are not necessarily predictive of the results in our ongoing studies. It's important to remember that all cognitive impairment is common across Huntington's disease and Alzheimer's disease. The underlying pathophysiology and symptomatology of these diseases are very distinct. We look forward to data across the Dalsan-Emder program expected throughout 2024, as well as top-line data from our Kinetic II study in essential tremor expected mid-2024. I'd now like to focus on a very encouraging area of opportunity for SAGE and for women with PPD. As you'll soon hear from Chris, the launch of Zuzube is off to a strong start, as is reflected by our first full quarter performance. I'm inspired by the positive anecdotes and success stories we're starting to hear from women with PPD who have been treated since launch. The impact of Zuzube on these moms and their families is profound, and it's energizing all of us. we continue to believe Zirzuve is the key to unlocking the blockbuster potential of PPD, enabling us to help many women suffering from this devastating disease. While early, we're beginning to see signs of practice patterns changing, particularly among OBGYNs. With approved oral treatment specifically for PPD, we believe healthcare prescribers have started to shift from suspect and refer to screen, diagnose, and treat. I'll highlight a few of the encouraging signals we're seeing in the first quarter of launch. Demand in PPD has been strong and continues to grow. Interest among healthcare prescribers with whom we've engaged or who have learned about Zirzuve has been high, evidenced by Zirzuve being prescribed for women with PPD across a wide range of healthcare prescribers. We're also highly encouraged by the progress we've made with commercial and government payers. Payers are beginning to develop policies, and for the majority of plans to date, we're not seeing onerous prior-offs or step-adds to PPD. Our teams in the field remain busy engaging with critical stakeholders, educating prescribers, and contributing to the recognition of PPD as an urgent medical condition. We believe the PPD opportunity is significant and have thought broadly about the initiatives needed to achieve commercialization success with Zerzuve. Our strategy is to launch with a focused approach and scale as we see success. As the early signs of launch have been encouraging, we've been increasing our marketing and non-personal promotion resources. If the positive trends continue, we believe additional scaling this year makes sense. Our goals are clear. Establish Zerzuve as the first-line therapy and standard of care for women with PPD and advance our brain health pipeline. Our work is more important than ever, and the countless lives we have potential to positively impact continues to serve as our North Star. With that, I'll turn the call over to Chris to provide additional context on the ongoing commercialization of Zerzuve. Chris? Thanks, Barry.
spk05: The Zerzuve launch is off to a strong start and exceeding expectations. We've made important progress during the first full quarter of commercial availability, and I'm excited to share our recent launch accomplishments and ongoing initiatives. As we've engaged with healthcare professionals, patient advocacy organizations, payers, and policymakers, our mission is clear. There is desperate need and critical gaps in care for women with PPD. SAGE is committed to working with all stakeholders with the goal of rapid affordable access to Zerzuve for women with PPD, as there often can be incredibly heartbreaking and unintended consequences for the mother, her baby, her family, and future generations when PPD is not adequately treated. It is critical to diagnose, treat, and provide care and support for all women with PPD. We're beginning to see the initial signs of hope and progress in the first few months following the launch of Zerzuve. As Barry noted, we are starting to see signs of practice patterns changing, particularly among the OBGYN community. In a short period of time, we believe we are already beginning to see PPD move from a disease where some HCPs would suspect PPD and then refer the patient for evaluation and treatment to a disease that HCPs are confident to diagnose and treat. I'm proud to be part of this important movement and grateful for the countless agents working to accelerate our impact in collaboration with our partner Biogen. As we said previously, our goal is to establish Zerzuve as the first-line therapy and standard of care for women with PPD. We believe we are already making meaningful progress. Before I dive into the specifics of early launch performance, it's an important reminder to note that IQVIA data does not reflect all shipments of Zerzuve. The key takeaway is that right now there is variability in the data and it may not provide a complete picture of Zerzuve demand in PPD. Even in the future, we see potential for variability in the data. With that said, I'm now excited to share more detail on the encouraging progress seen during our first full quarter of launch. Zerzuve generated $12.4 million in total revenue, of which Sage recognized $6.2 million in collaboration revenue during the first quarter of 2024. In the first quarter, there were more than 1,200 prescriptions written. The growth in prescriptions this quarter was strong and reflective of the interest and enthusiasm we're seeing for Zerzuve in the treatment of women with PPD. While we believe the number of prescriptions is an important early indicator, in the coming quarters as the launch matures, we plan to focus primarily on shipments and collaboration revenue. We were pleased to see prescribing across a wide breadth of HCPs who treat PPD with the largest percentage of prescriptions coming from OBGYNs. OBGYNs are on the front line of care for women with PPD and are often the first opportunity for an HCP to recognize symptoms, diagnose, and treat. As we know, the patient journey can vary greatly for women suffering from this disease. We also continue to expect growth in prescriptions from psychiatrists and PCPs who are also actively diagnosing and treating women with PPD. Further, we are encouraged that the breadth of adoption of Zirzuve in the treatment of PPD continues to grow, with the number of new Zirzuve prescribers increasing each month during the first quarter. We are also beginning to see signs of depth with repeat prescribing. A growing number of HCPs have already written multiple prescriptions for Zirzuve. Based on early claims data, we see that many Zirzuve patients appear to be receiving Zirzuve as first-line therapy for PPD. As of the end of the first quarter, more than 700 prescriptions were shipped and delivered to patients. Our goal is to get Zirzuva to women with PPD who are prescribed the medication as quickly as possible, and we continue to make improvements intended to help optimize the experience for HCPs and patients. This includes educating HCPs on the specialty pharmacy system, as well as operational improvements designed to expedite prescription processing. We expect the process will get better and quicker through these efforts and as formulary coverage decisions are made. Working towards broad and equitable access for women with PPD continues to be a key priority, and we know access is critical for a successful launch. Conversations continue to advance at an accelerated pace across national, regional, and government payers. Notably, two of three national PBMs have published policies for Zerzuva and PPD without step therapy or complex prior authorization, and we're progressing in conversations with the third national PBM. We're encouraged by similar trends with national and regional insurers. Today, we have over 65% of commercial lives covered for Zerzuva and PPD, with the majority having no step therapy or complex prior authorization, and we expect this number to increase over the coming months as we continue engaging with payers who have not yet published policies. With respect to Medicaid, we are pleased to see almost half of the states, including several of the largest states, have completed reviews much more quickly than is typically seen for a product launch. While Medicaid policies continue to develop, most states that have made a decision to date are covering Sersuve for women with BPD, in line with our expectation of no-step therapy and no complex prior authorizations. Where Medicaid policies are in place, we are seeing most women with PPD access Zerzuve at a nominal cost or zero copay. We expect the majority of Medicaid coverage decisions in PPD by the end of the year. We believe the strong payer progress we and Biogen have seen to date is the result of our active and longstanding engagement with payers, our knowledge of the PPD market, and the strong value proposition for Zerzuve in the treatment of women with PPD. It is also critical that we continue to work to enable access to Zerzuve for all women with PPD who are prescribed treatment, regardless of financial means and coverage, for our patient support and financial assistance programs for those who are eligible. While we did see use of these programs, the majority of shipments were covered by commercial and government payers in the first quarter, even as coverage policies were being developed. We anticipate that if formulary coverage decisions continue to be favorable, And as the SP process is further optimized, the need for the functionally uninsured program will decrease over time. Lastly, I'm excited to share some color on our ongoing marketing efforts. Based on our experience, we believe this is a highly promotionally sensitive market, which benefits from the surround sound of omnichannel effort. We continue to see enthusiasm from HCPs to learn more about Zerzuve and have expanded commercialization efforts across stakeholders. with the goal that Zerzuve is top of mind as first choice treatment for women with PPD. For example, we have executed ACP peer-to-peer live and virtual branded educational platforms, attracting wide attendance across multiple specialties that treat women with PPD. We also launched our fully operational Zerzuve.com healthcare professional website at the end of February, in conjunction with several media drivers encompassing paid search, programmatic displays, banner ads, and HCP-targeted email. Recently, we launched the zurzuve.com full consumer website, where women with PPD can find branded education, support resources, and opt in to receive proactive zurzuve communications. We're highly encouraged by what we're seeing so far, and the launch has reaffirmed our belief that zurzuve is an important treatment option to address the urgent and profound unmet need for women living with PPD. We want to build on the momentum we have seen in the first full quarter of launch to reach even more of the women with BPD who need Zirzuve. We know we have more work to do to get there. We know that women living with the disease cannot afford to wait, and now with Zirzuve available as a treatment option, they should not have to. I look forward to sharing additional details in the coming quarters. With that, I'll turn it over to Laura for a more detailed discussion of our recent pipeline progress. Laura?
spk08: Thanks, Chris, and good morning, everyone. As a clinician, I've seen firsthand the challenges that women with PPD and their families face, and so it is gratifying to see the impact we are already making for these women. I'm excited to be part of such a significant moment in maternal health as we continue to execute on the launches through Zubay and PPD. I'll now turn to Dalsanemdor, our wholly-owned, first-in-class NMDA receptor positive allosteric modulator, or PAM, as a potential oral therapy for certain cognitive disorders associated with neurodegenerative disease. Last week, we reported top-line data from the PRECEDENT study, a double-blind, placebo-controlled Phase II study in people with mild cognitive impairment, or MCI, in Parkinson's disease. After six weeks of treatment, patients who received Belzenendor did not demonstrate a statistically significant difference from baseline compared to placebo. on the primary endpoint, the WAIS-IV coding test score at day 42. Based on the data, we do not plan any further development of Delzenendor and Parkinson's disease. As we said on our call last week, it is important to remember that these results are not necessarily predictive of the results we may see in our ongoing Huntington's disease and Alzheimer's disease studies, given the very distinct underlying pathophysiology and symptomatology of these diseases. While we're disappointed by the results of the precedent study, we continue to believe in the potential of Dalsimandor and the other indications we are studying, and look forward to the various data readouts anticipated later this year. Specifically, in mid-2024, we expect to report top-line data from the Surveyor study, a Phase II study designed to generate evidence linking cognitive performance to real-world functioning in people living with HD. In late 2024, We expect to report top-line data from the LightWave study, a double-blind, placebo-controlled Phase II study of dalsanemdor in people with MCI and mild dementia due to Alzheimer's disease. We also expect to report top-line data in late 2024 from the Dimension study, a double-blind, placebo-controlled Phase II study designed to evaluate the efficacy of dalsanemdor in cognitive impairment in HD over a three-month treatment period. As we've described previously, we want to underscore that the primary objective of the Surveyor Study is to understand the magnitude of the cognitive impairment in HD relative to healthy individuals. A key secondary objective is to advance our understanding of the effects of dalsanemdor on cognition and function in participants with HD. It's important to emphasize that the Surveyor Study is not designed nor powered to show statistically significant differences between dalsanemdor and placebo. These data are meant to complement the dimension study by generating evidence to better define clinically meaningful change and the relationship between changes in cognition and function. We look forward to sharing these results with you as they become available. I'll now turn to SAGE324, an investigational positive allosteric modulator of GABA-A receptors with potential in the treatment of essential tremor, or ET. We are developing SAGE324 in collaboration with Biogen. There has been a lack of innovation in treatments for ET with no new approved treatments in more than 50 years. Essential tremor can have a significant impact on an individual's ability to perform everyday tasks. Developing new treatment options that could help an individual maintain his or her quality of life, daily functioning, and independence is critical. Following the encouraging data from our completed kinetics study, which demonstrated statistically significant reduction from baseline in upper limb tremor amplitude, we look forward to seeing the data from the Kinetic II study. This study is a three-month study designed to identify a dose with a safety and tolerability profile that is suitable for chronic dosing and further development of stage 324 as a potential treatment for ET. We look forward to sharing this data expected in mid-2024. Lastly, I'd like to reiterate our excitement around our earlier stage pipeline, including SAGE 319, our extra synaptic preferring GABA-A receptor PAM, and SAGE 421, our NMDA receptor PAM. We look forward to sharing more about these programs as they progress. With that, I'll turn the call over for a review of our financials.
spk13: Kimmy? Thanks, Laura. Our financial results for the first quarter of 2024 are detailed in our press release issued this morning. Before diving into the financials, I want to share my excitement around the launch of Zerzuve and the opportunity to help so many women suffering with PPD. We in Biogen are mobilized with the goal of capitalizing on early success and jointly supporting the launch of Zerzuve in the United States. Commercialization of Zerzuve remains a key priority for us as we work to expand access in the treatment of women with PPD and build momentum. We also plan to continue to make disciplined pipeline investments backed by data to support our goal of near, mid, and long-term value creation. I'll now turn to the financials. Today, we announced collaboration revenue in Q1 from sales of Zerzuve of $6.2 million. Our reported collaboration revenue is 50% of the net revenues Biogen reports for Zerzuve. As a reminder, net revenues are recorded by Biogen when Zerzuve is shipped to the wholesalers and are not calculated based on the number of shipments to patients or prescriptions written for Zerzuve. Net revenues for the first quarter can be attributed to a combination of wholesalers purchasing Zerzuve to fill orders as well as building inventory and anticipation of increasing demand for Dersuve in the treatment of women with PPD. We're not guiding today on gross to net, other than to say, given the fact that Dersuve is a novel medication and the only oral treatment specifically approved for women with PPD, we do not anticipate the type of discounting we see for other branded CNS agents. Turning to operating expenses. R&D expenses were $71.7 million in the first quarter of 2024. SG&A expenses were $52.6 million in the first quarter of 2024. The decrease in both R&D and SG&A expenses compared to the first quarter of last year was primarily related to decreased headcount, overhead in technology, as well as decreased spend on the early stage pipeline, the ran alone clinical trials, and manufacturing. primarily as a result of the Q3 2023 restructuring. As we've previously stated, we expect operating expenses to decrease in 2024 relative to 2023. Our net loss for the first quarter of 2024 was 108.5 million, and we ended the first quarter of 2024 with cash, cash equivalents, and marketable securities of approximately 717 million. We are reaffirming that based on our current operating plan, we anticipate cash, cash equivalents and marketable securities, anticipated funding from ongoing collaborations, and estimated revenues will support operations into 2026. As we said on our last earnings call, we do not anticipate receipt of any additional milestone payments from collaborations in the remainder of 2024. Before I turn the call over for Q&A, I want to reiterate that we remain dedicated to progressing our mission of better brain health for patients. Further, we believe we have a strong financial foundation as we continue to progress through our catalyst-rich year for SAGE. We look forward to providing updates on our progress in the coming quarters. I'll now turn it over to Ashley to handle Q&A with the operator. Ashley? Thanks, Kimmy.
spk10: I'll ask that you limit yourself to one question. If you have an additional question, feel free to return to the queue. Now, I'll turn it over to the operator to handle Q&A. Operator?
spk22: Thank you, and if you would like to ask a question, please signal by pressing star one 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, you can press star one to ask a question. and we'll pause for a brief moment to allow everyone an opportunity to signal for questions. And our first question is coming from Yasmin Rami with Piper Sandler. Your line is open.
spk09: Hi, guys, good morning. This is Lauren on free as just a quick 1 for us for the kinetic to study. Have you guys guided any powering assumptions? And with that, have you. Detailed and efficacy and safety signal that would warrant moving forward into phase 3 and then just coinciding with that. Have you started to engage with the FDA and in regard to a phase 3 for this program? Thank you.
spk06: Yeah, Lauren, thanks for the question about SAGE-324, our GABA PAM meant for chronic administration that's partnered with biogen and movement disorders, initially starting with the essential tremor. Laura, you want to take the question?
spk08: Yeah, sure. So with regard to the study design, we have provided study design details on clintrials.gov, and it's also in the investor deck that's on our website. We don't provide additional information beyond what's available there. For Phase 3, of course, in any development program, as you come close to finishing Phase 2, you start to think about Phase 3 planning. We are certainly doing that in conjunction with Biogen. And as part of that, we are engaging experts.
spk06: Yeah, and the key to Kinetic 2 is a follow-up from the Kinetic study where we saw at 28 days a statistically significant improvement in tremor amplitude as well as activities of daily living. Kinetic 2 is now, we want to see that at three months. And the real key is to make sure that we have a benefit-risk dose to move forward for chronic administration. So that's really what we're looking for out of Kinetic 2.
spk07: Perfect. Thank you. I'll hop back in the queue. Thanks, Lauren.
spk22: Our next question is coming from Anna Pam Rama with J.P. Morgan. Your line is open.
spk04: Hey guys, thanks so much for taking the question. One of the key questions we've gotten sort of post Biogen and your guys' report this morning is any more color on the inventory build in the quarter versus the orders filled for Zerzuva and how we should think about this moving forward. Thanks so much.
spk06: Yeah, Anupam, thanks for the question and we share your enthusiasm off to the strong start. I'll turn it over to Kimmy to talk about that, and then I'll provide some color. Kimmy?
spk13: Yes. Well, thanks, Barry. Zerzuvi generated $12.4 million in total revenue, of which Sage recognized $6.2 million in collaboration revenue during Q1, which we talked about during our opening remarks. The net revenues for the first quarter can be attributed to a combination of wholesalers purchasing inventory to fill orders, as well as building inventory. And that's, of course, in anticipation of increasing demand for Zerzube in the treatment of women with PPD. As the launch progresses and we have a better understanding of the demand and inventory levels, we'll be able to share more at that point.
spk06: Yeah, and I just did have some color there, Anna. It's an important question. I know it's gotten a lot of attention. I will comment that the wholesalers are very smart. They don't want products sitting on the shelves. and aging. So we really believe what we're seeing is demand driven.
spk07: Thanks so much for taking our question and congrats on the strong launch. Thanks, Anupam.
spk22: Our next question is coming from Salveen Richard with Goldman Sachs. Your line is open.
spk12: Hi, this is Srinath Rao for Salveen. Thank you for taking my question and congratulations on the quarter. Could you speak to the process through which OB-GYNs are diagnosing PPD, and at what point are these visits happening? Is it proactive on the part of the doctor or the patient? And also, any general feedback you've received from doctors on the efficacy and safety profile?
spk06: Yeah, Srinath, I'll start, and then I'll see if Laura or Chris want to add any color after I answer it. What's really important and what you've highlighted here is that healthcare providers in general are recognizing that PPD is a medical condition with urgency to treat and it's not a moral failing, and that theme is critically important. The other practice pattern that we've highlighted, and this is really important, is that OBGYNs, who are the front line of seeing moms with potential for PPD, are moving from the practice pattern of suspecting depression and referring to either primary care or psychiatry, to screening, diagnosing, and treating. And that paradigm shift continues when we see it accelerating. So that's really, really important. In terms of what's happening out in the real world, we've got a lot of anecdotes, and lots of anecdotes don't add up to data per se, but it does give us a flavor. What we're hearing from the field is that Zerzuve is performing in the real world as it performed in our clinical trials, and that is a very broad benefit-risk profile, rapid onset as early as two or three days, and that women appreciate this is a 14-day course of treatment or completing that treatment.
spk05: Yeah, what I would add, and I included in my opening remarks, is that in the first quarter of 2024, we saw that OBGYNs accounted for the largest percentage of prescriptions. As Barry noted, that's important because what that begins to signal is that treatment practice for women with PPD is beginning to change as you have OBGYNs on the front line of care for so many of these women. I'd be remiss, though, if I didn't mention that we expect krillton prescriptions from psychiatrists and PCPs as well as OBGYNs moving forward as they continue to actively diagnose and treat women with PPP, representing more broadly the adoption for Zirzuve and really the need to change the way that we think about and treat PPD moving forward, so encouraged by all of those physicians really leaning in.
spk08: Yeah, and Chris, I would add that when you think about diagnosing PPD, there actually are a lot of tailwinds, and those tailwinds come from professional organizations like ACOG and the American Academy of Pediatrics that have both issued guidance practice guidelines that suggest that patients should be screened throughout their pregnancies and in the postpartum period. In the case of AAP, they recommend that the moms are screened at all the well child care visits. So in most healthcare settings at this point, this routine screening is happening, which enhances the ability to detect women with PPD earlier in their disease evolution.
spk06: Thanks, Renata. It's a great question. And as you're hearing, we're pretty excited by the paradigm shift that we're accelerating with Zerzube.
spk12: Thank you for the call.
spk22: Our next question is coming from Ritu Barau. With TD Cowan, your line's open.
spk02: Good morning, guys. Thanks for taking the question. I wanted to ask about the difference between the 1200 prescriptions written and the 700 shipped and delivered. How should we think about the delta there? Are those prescriptions that may result in free drug? Are those prescriptions that are right now sort of in that time to fill period? And can you comment on percentage-free drug and that time-to-fill period? Thanks.
spk06: Yeah, Richie, thanks for the question. Let me start with Chris, see if Kimmy has anything to add on free goods, and I'll loop back to the end.
spk05: Yeah, so as we noted, Zirzuva's launch is off to a strong start and exceeding expectations. And we're encouraged by the breadth of adoption of Zirzuva and the treatment of PPD and see it continue to grow with new prescribers each and every month. and not just new prescribers, but a number of repeat prescriptions coming from many of those same providers as we move forward. As you note, Ritu, with respect to written versus shipped prescriptions, you always expect, particularly at a launch, there to be a delta between written and shipped prescriptions, although over time what you would anticipate is that would actually catch up as the number of shipped prescriptions catches up with the number of written prescriptions. We continue to see a trend of growing prescriptions each month in Q1, with the 700 prescriptions that were actually shipped and delivered to patients, and we'll see that number catch up to the prescriptions that were actually written. Our goal really is to ensure that Zirzuve gets to all women who are prescribed the medication as quickly as possible, and we continue to make improvements to, in effect, the system that we have in place to optimize the physician-patient experience, to make sure that the SP model is working as efficiently and effectively as possible, and as coverage policies come online where There aren't onerous prior authorizations and step edits. The medication flows from prescription to shipment quicker and quicker with each successive day. So really excited about the work that we're doing behind the scenes to make that happen because moms deserve to have this medication. Women with PPD deserve to have this medication as rapidly as possible.
spk07: Okay, great. Thanks, Ritu.
spk22: Our next question is coming from Laura Chico with Weblish Securities. Your line's open.
spk16: Hey, good morning, guys. Thanks very much for taking the question. I guess one thing you mentioned in the prepared remarks centered on potentially scaling up the Salesforce at a given point, but trying to better understand what type of metrics would you need to see to warrant kind of scaling up? And then kind of related to that, how far from symptom onset are women typically receiving a Zerzuvae prescription? I realize that might change over time, but just curious how... At what point from diagnosis are they getting the prescription? Thanks.
spk06: Yeah, Laura, thanks for the couple questions there. I'll start and see if Chris wants to add a quote. Let me start with the second point. So, you know, we don't have solid data on the exact timing from onset of symptoms of treatment. The great sign we're seeing, however, is the number of scripts coming from OBGYN. can imagine the patient journey here if if a woman who has previously suffered depression therefore is at risk suffers PPE you might expect that the diagnosis and prescription comes from her treating primary care prescribed or primary care office or or psychiatrists the fact that we're seeing the OBGYNs prescribed and that about half of the women treated this early claims data so take it with a grain of thought but about half the women treated were naive, meaning they had not been on antidepressant the last year, suggests to us that the PPD is being picked up fairly early on in the treatment, in the landscape here. So that's a great sign. Back to your first question, you know, as we talked about, we really do believe that Zirzuva is the key to unlock the blockbuster potential of PPD, helping as many moms as we can. As you know very well, Laura, we started with a focused approach, and we're already scaling. As we highlighted earlier, We've increased our personal, non-personal promotion, as well as some of the other efforts around specialty pharma and others, which Chris talked about. So we're excited. As we see continued prescribing patterns, we invite you. We'll talk about field force and other aspects of expansion. You'll hear about that in the quarters to come.
spk07: Thank you. Thank you.
spk22: Our next question is coming from Paul Matisse with Stifel. Your line is open.
spk14: Hey, thanks so much. I was wondering if you could expound upon what this mid-year Huntington's readout is going to look like. Like, what are the key couple analyses that you're going to be doing? And more specifically, I was wondering if you could sort of talk about your current thinking on endpoints, and specifically the HD-CAB, which I think you're using as a primary in dimension, but But more recently, another company in the space had trouble getting the FDA on board with that measure. Thank you.
spk06: Yeah, Paul, thanks for the, I guess, the three or four questions in one. Let me turn it over to Laura to tackle the DALT and MDOR questions you're asking.
spk08: Sure. Thanks for the question, Paul. So, the Surveyor Study is the study that we expect to read out next in mid-2024. And that study is designed with a particular purpose in mind. It is designed to provide data to put context around the HD-CAB to help us understand what clinically meaningful change looks like. And so with regard to how we designed the study, there's really two parts. The first part is comparing baseline HD-CAB scores for healthy participants versus patients with Huntington's disease. And that, looking at that delta, is going to help us understand what the magnitude of the impairment is in this population and also help to anchor the meaningfulness of any improvements that we see in the study. The second part of the study takes those patients with Huntington's disease and randomizes them one-to-one to Dalsanemdor or placebo. Now, this is a very small group of people. 40 patients were randomized, so you're talking about 20 subjects in the arm. And they're treated for one month. And so what we're looking at here is looking at trends in the data. We're trying to understand how the magnitude of the change in cognition and how that pulls through to changes on the global measures and the functional measures. And again, these data are really important to help put the results of the HD-CAB in context.
spk07: I'll go to the next question.
spk22: Our next question is coming from Jay Olson with Oppenheimer. Your line is open.
spk00: Oh, hey. Congrats on the Zerzuve launch progress. Since PCPs are relatively less familiar with scheduled drugs for mood disorders compared to psychiatrists and maybe OBGYNs, Can you talk about the strategy for increasing Zerzuva awareness and prescribing among PCPs, and then any color you could provide on your strategy for DTC? Thank you.
spk06: I'll start, and then I'll kick it over to Chris. Thanks, Jay. We're also incredibly excited by the trends we're seeing with the launch of Zerzuva. As you highlighted, while a majority of scripts are coming from OB-GYN, we are seeing prescriptions from psychs. and primary care. And that pattern may shift over time, although we're very excited that OBGYNs, who are the front line of picking up depression in moms here, are the key prescribers. And we think that trend will continue. Now, I talked about the patient journey. So what we are likely seeing, if there's been a prior history of depression and the mom's diagnosed with a with depression in pregnancy or postpartum, and they're under the care of a psychiatrist or primary care physician, we're likely seeing scripts coming from that. If they're newly diagnosed, that's where the OBGYNs are coming in. Actually, you know, primary care are very familiar with prescribing antidepressants. In fact, the majority of SSRIs, SSRIs come from primary care versus especially just the volume. So they're familiar with it. They've got licenses. They're very familiar with scheduling. the scheduled drugs as needed. Chris, you want to add any more?
spk05: Yeah, I think the color that I would add to PCPs here, Barry, is the group of PCPs that we're calling on with the Salesforce right now. It's a core group of PCPs, frankly, who behave more like psychiatrists. They may be in a community where there is not a psychiatrist, and therefore they become the de facto clinician that treat many of these patients. But those are the PCPs that are being called on from a Salesforce perspective. Obviously, as I had mentioned in my prepared remarks, we're continuing to increase digital means in order to reach and broaden our reach and to increase our frequency across all physician types. And digital has been particularly effective in actually going forward and doing that and dialing up the investment in that over the course of the year is going to have that impact in terms of reaching PCPs as we go forward because we know oftentimes they're the ones who become the first line of care after a woman has seen her pediatrician or other types of clinicians seeing women outside of OBGYN psychiatry so we'll continue to invest in that I think your question around DTC is also an important one and certainly one I'm sure is on the mind of many people on the call here today we've talked about being focused work with our investment in scaling with success obviously the first step in this is making sure that we have a very well educated and prepared clinician audience so that when patients come in and ask for the medication by name that they're ready to effectively prescribe the medication with an understanding of the efficacy and the safety profile and You know, obviously the first step is educating clinicians. We use both personal and non-personal to do that. And when the time is right to expand DTC so that patients can go in and have that informed discussion, we'll actually invest in that. What I would be remiss, though, if I didn't mention was the helping tailwind that we have with respect to online and social media activity in and around Zerzuwe. This is a popular topic of conversation. In many senses, that's going to precede and has preceded the DTC effort that we know will come in the future. And when the time is right, we'll invest in DTC and move it forward.
spk00: Thank you. Super helpful. Congrats again.
spk07: Thanks, Jay.
spk22: Our next question is coming from Ami Fadia with Needham. Your line is open.
spk11: Hi, good morning. Thanks for taking my question and congrats on the progress on the ZOE. Sorry about that. Could you talk a little bit more about the use of ZOE in first line versus second line? And in what situations do patients get ZOE as a second line treatment? And are they getting it in combination with any existing SSRI, SNRI treatments? And just to follow up from an earlier topic, could you sort of go over in what way the survey or data will inform the dimension study?
spk06: Thanks. Let me start with your Zuby question, then I can ask Laura to talk about the Dowson-Ember question. As we stated, Zirzuva is the first and only oral medication specifically approved for postpartum depression. Our goal is for Zirzuva to be used frontline. And what we're seeing from a payer perspective is, in fact, support of that. As Chris highlighted, we're seeing a very strong payer coverage. I call them kind of payer tailwinds with no steps for majority of cut plans and very limited prior offs. So that's a very important thing. We're seeing women step up to be treated. We're seeing healthcare prescribers prescribed and OBGYNs leading that chart. So all signals are that Zuzuvay is becoming a frontline first choice for the treatment of postpartum depression. I highlighted this earlier, but when we look at early claims data, almost half of the claims data suggests that those being prescribed Zuzuvay already in the first quarter, which is pretty remarkable, have not had an antidepressant for the previous year. So we are seeing the trend for Zuzube to be used frontline and really no obstacles to make that happen. Laura, you want to talk about DELS and MDAR?
spk08: Sure. So your question is related to how Surveyor will inform the dimension study. And I think there are really two main ways that we would see this happening. The first is we will get some data that will help us understand the performance of the different scales that we've included in the studies because the scales included in dimension and surveyor are largely overlapping. The second is, as I mentioned earlier, we'll be looking to really better identify clinically meaningful change in patients with Huntington's disease on the HD-CAB and other endpoints. And so that will help inform the data interpretation from dimension. Of course, when we get the surveyor data, we're going to learn as much as we can from it. But we don't have plans at this time to change the dimension study design.
spk07: Would you change any part of the function for dimension?
spk08: As I mentioned, we'll learn as much as we can from the data, but we don't have plans right now to change the study.
spk07: Thank you.
spk22: Our next question is coming from Brian Abrams with RBC Capital Markets. Your line is open.
spk21: Hey, good morning, guys. Thanks for taking my question, and congrats on the early progress of the launch. I'm curious, what are you seeing in these early days as the biggest reasons why a diagnosed PPD patient might not receive a written prescription for a course of Zuzube? Is it a matter of awareness or coverage? Are there certain types of Practices or regions where these are they're more later adopters tend to be later adopters versus early adopters I'm curious what you're seeing on the ground there.
spk05: Thanks Yeah, Brian, thanks for the question and I appreciate the the congratulatory note Chris you want to take that yeah So so let me start with the payer piece here because I think I think it's important to highlight this I think with respect to where we stand today We're in a very privileged position with this medication and it's launching and around payer coverage as I noted in my prepared remarks that We're encouraged by the progress that we've made with commercial and government payers. We know that as payers are beginning to develop policies, the majority that we've seen today don't come with onerous prior authorizations and step edits. And importantly, that enables a clinician when he or she wants to prescribe the medication to choose their first line. And we have 65% of all commercialized coverage. That's 180 million lives that are already under coverage with the majority of those being or most of those being plans that don't have onerous prior authorizations and step edits. So from a commercial perspective, we're in good shape. Also with Medicaid, we see that with respect to the Medicaid coverage that we've had, that over the first quarter of the year, almost half of the Medicaid states, including several of the largest states, have already completed reviews. And again, those don't come with onerous prior authorizations and step edits, effectively meaning that patients can get access to this medication both equitably and affordably as we go forward. So what I would say is, to sort of round out my response, is that ultimately if a physician hasn't prescribed Zirzuva yet, it's a matter of getting to that clinician with the education that's needed ultimately to understand the efficacy and safety profile of the medication. Between what we're doing from a personal promotion perspective and now with increased and ongoing investment in non-personal efforts in addition to what we're seeing from what's being communicated socially and online, we believe that we're going to be able to enact that change to help a clinician who may not have heard the message hear it and begin to prescribe Zirzuva.
spk06: Yeah, Brian, just to round that out, I'd say that just like in drug development, the biology of the launch is working, meaning patients are advocating, healthcare prescribers, particularly OBGYNs, are prescribing, and payers are paying, as Chris highlighted. The rest of it is classic engineering of a launch. We need to get reach and frequency to educate. And as you very well know, changing healthcare provider practice behavior is the key to success, and that's what we're in the midst of doing.
spk07: Thanks, Barry. Thanks, Chris. Thanks, Brian.
spk22: Our next question is coming from George Farmer with Scotiabank. Your line is open.
spk19: Hi. Good morning. Congratulations on all the progress. I was wondering if you could comment on expanded geographies for Zuzube and how that might be progressing and what other steps might be necessary. I think Brian mentioned maybe another trial would be required. I was wondering if you could potentially comment on that.
spk06: So, George, when you say geography, you're talking about ex-U.S.?
spk18: Yeah.
spk06: Yeah, so I'll remind you that the relationship that we have, the partnership that we have with Biogen is we're 50-50 co-co in the United States. You've heard over and over that's going incredibly well. And outside Japan, Korea, and Taiwan, where we have another partner, Biogen is responsible for the rest of the world. So it's really a Biogen question to answer.
spk07: Okay, thanks. Thanks, George.
spk22: Our next question is coming from Sumat Kakarni with Canaccord. Your line is open.
spk18: Good morning. Nice to see the progress on Zazuve, and thanks for taking my question, which is on Dazenemdar. So other than some factors you mentioned before that might make read-throughs to upcoming trial readouts challenging, is there anything specific that makes cognitive impairment in Huntington's and Alzheimer's different versus Parkinson's? I'm asking because there are most likely some nuances involved in specific areas of neuronal loss in these disease states, and to see if there's a potential mechanistic basis for DALZEN to target specific parts of the brain in different ways.
spk06: Yes, well, thanks for the congratulations, Zub, and great question on DALZEN and EMDR, and a very important one. Let me ask Mike to start with sort of the biologic appreciation that started in Huntington's with 24-second cholesterol, and maybe Laura can talk about that. why we think the results we see are not necessarily predictive of future results. Mike?
spk03: Thanks, Barry. So what I would say is that there are decades of research that have really implicated NMDA receptor hypofunction in a range of disorders associated with cognitive impairment. And further, there's increasing evidence specifically of NMDA receptor loss or expression changes in disorders such as Huntington's disease, Parkinson's disease, and Alzheimer's disease. That being said, While cognitive impairment is a common feature across these diseases, the underlying pathophysiology and the relative contribution of NMDA receptor dysfunction is likely to be distinct across these groups. And we really have different hypotheses that we're testing across the three studies that we're running. And so for this reason, we've always seen the studies in HD, Parkinson's disease, and Alzheimer's disease as distinct and independent tests of the NMDA receptor hypofunction, where we're really looking at different pathophysiological consequences there. So, as Barry mentioned, in the context of Huntington's disease, which is our lead indication, we're really focusing on the loss of the endogenous modulator 24S hydroxycholesterol as the rationale for why a molecule such as dalsanemdir should work in treating these cognitive impairments. So that's sort of the scientific rationale across these disease. I'll let Laura comment a little bit more about this distinct symptomology as we think about the disorders.
spk08: Right. So these disorders obviously are all characterized by cognitive impairment, but they have accompanying symptoms that are quite different across. As we talked last week about Parkinson's disease, that's a disorder where you see the onset of cognitive impairment after motor symptoms appear in most cases. In Huntington's disease, the reverse is true. the onset of symptoms can be 10 or 15 years even before the onset of the motor symptoms. And so it's a very different progression. You're looking at a younger population. You're also looking at a much more homogeneous population based on the underlying etiology. And then you move over to Alzheimer's disease, a very different population again in terms of the underlying pathophysiology. We have the amyloid plaques and the neurofibrillary tangles, which are driving the downstream pathophysiology downstream pathology and NMDA receptor hyperfunction, but that is a very distinct driver compared to Huntington's and Parkinson's. So, for all these reasons, as Mike said, these are really distinct disorders with differences in the symptomatology, differences in the study design, and we expect that each of these is an independent test of the hypothesis. Thanks.
spk07: Thanks, Simone.
spk22: Our next question is coming from Yatin Sanaje with Guggenheim. Your line is open.
spk01: Thank you for taking my question and congrats on the nice launch. Question on 324 with regard to the Kinetics 2 study. Could you maybe help us understand the difference between the endpoint between Kinetic and Kinetic 2, what you would like to show? And then how should we think about pivotal endpoint, because I think there are other companies that are using ADL as an endpoint for pivotal development. So anything you can talk from the regulatory perspective on the endpoint channel would be great. Thank you.
spk06: Yeah, yeah, Tina, and thank you for congratulating on the launch. Laura, you want to take the – thank you for your question?
spk08: Sure. So with regard to the original kinetic study and the Kinetic II study that's currently ongoing, we actually use the same primary endpoint, which is the upper limb extremity score from the Tetris performance scale. We use that measure because it's a sensitive measure to detect change. We are aware, as you are, that there has been regulatory feedback about using the ADL scale associated with the Tetris. We are collecting all of that data in the ongoing Kinetic II study And we will be poised with a lot of data to have discussions with regulators at the end of phase two about which instrument would be the best for a phase three endpoint.
spk07: Thank you, Atene.
spk22: Our next question is coming from Douglas Hull with HC Wainwright. Your line is open.
spk20: Hi, good morning. Thanks for taking the questions and congrats on the progress. Just curious, what percentage of the overall sort of sales details so far have been made by you versus Biogen? And I'm just curious in terms of how, when you contemplate sort of scaling up the launch, how do you coordinate that and sort of determine the needed resources?
spk06: Let me start and then So I was actually with our field team a couple weeks ago, and I can tell you that whether you're sage or biogen, they're working incredibly well together as a well-functioning machine. And the team is very well integrated. They're helping each other literally every day to do what's right, which is help moms get diagnosed and treated with Zirzuva as quickly as possible. So it's a very well-coordinated effort. Chris, you want to talk, we've talked about this before, you want to just mention the scaling aspect?
spk05: Yeah, I think in terms of the activity at a field level, it's 50-50 between the two organizations. You know, we really work well and collaboratively around how we execute at a field level with respect to reach and frequency. I think in terms of scaling, those are conversations that are ongoing. The teams talk about the future of this product on a daily basis. And it's everything from the strategy that we employ all the way through to the tactics that and specifically how we're going to execute. And again, I think it's very noted, that's an ongoing interaction between the two organizations that are committed to fundamentally changing the way PPD is thought about and treated for women that are suffering with the condition.
spk07: Okay, great. Thank you.
spk22: Our next question is coming from Vikram Pruhit with Morgan Stanley. Your line is open.
spk17: Hi, thanks for taking my question. This is Morgan on for Vikram. So, on reimbursement for Zerzuve, I know you had mentioned not guiding to gross-to-net just yet, but where would you expect steady-state gross-to-net to potentially settle out and how long do you think it would take to reach this steady-state? Thank you.
spk06: Thanks for the question, Morgan. Kim, you want to take that?
spk13: Yeah, as we mentioned, and as you just mentioned, we are not guiding to gross to net today. But, you know, again, we've been talking about the fact that we don't anticipate those kinds of discounting that you're seeing for recent branded antidepressants. And another thing is if you think about the key components of what we expect in our gross to net, they're the typical components. They're the rebates and discounts we'll see, the patient assistance programs. you know, including financial assistance. So all the similar kinds of things you'll see, but we just don't anticipate the same type of discounting you see for the other recent antidepressants.
spk07: Thanks, Maureen.
spk22: Thank you. And that will conclude the Q&A portion of today's call. With that, I will turn it back over to Mr. Green for closing remarks.
spk06: Thanks, Shelly, and thanks again to everyone for joining us this morning to review our results from the first quarter of 2024. Just to close it out, the full quarter of Zerzuva launch has been completed, and we remain highly encouraged with the progress, and we're excited to help the many moms suffering with PPD. Of course, we were disappointed with the outcome of the precedent study, but as you heard from Mike and Laura, we remain on track. to read out important data from across our pipeline throughout the remainder of the year. And we do not believe the precedent is necessarily predictive of future studies, as you heard on the call. We're also well-positioned financially to take us through key milestones, and we remain focused on our mission to develop and launch life-changing brain health medicine so every person can thrive. Thanks again, everyone, and have a great day. Bye.
spk22: This concludes today's call. Thank you for your participation. You may now disconnect.
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