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spk13: Good morning. Welcome to Sage Therapeutics' fourth quarter and full year 2023 Financial Results Conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Sage's website at sagerx.com. This call is the property of Sage Therapeutics and recording, reproduction, or transmission of this call without the express written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Ashley Kaplowitz, Executive Director of Investor Relations and Capital Markets at Sage.
spk14: Good morning, and thank you for joining Sage Therapeutics' fourth quarter and full year 2023 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 fourth quarter and full year 2023. Our Chief Business Officer, Chris Bonecki, will provide an update on the ongoing commercialization of Zerzube. We will also be joined by Laura Goltz, our Chief Medical Officer, who will review recent progress in development activities across our program. We will then be joined by Kimia Gucci, our Chief Financial Officer, who will review the financial results from the fourth quarter and full year 2023. 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.
spk16: Thanks, Ashley, and thank you, everyone, for joining us this morning. 2023 was a pivotal year for SIGS, highlighted by the approval and commercial availability of our second FDA-approved product, Zirzuve, the first and only oral treatment approved specifically for adults with postpartum depression, or PPD. We have a big year ahead of us and even greater potential to build a leadership position in brain health and a top-tier biopharmaceutical company. Our reach and expertise across various brain health conditions are key to our work to unlock potential breakthroughs to help patients suffering from a wide range of brain health diseases. Brain health diseases are one of the leading causes of disability worldwide, yet novel treatment options in care remain limited. We are seeking to change that with a pipeline designed to address brain health disorders and improve public health. Brain health is fundamental to well-being and function at each stage of life. For pioneering science, we aim to advance programs that have the potential to improve the lives of individuals living with brain health disorders and their families. We're focused on modulating brain network function and disruptive circuits, an underlying factor in many brain health disorders. Starting with compounds that selectively modulate GABA and NMDA receptor activity, our expertise in neuroactive steroids includes oxyscalal chemistry, allowing us to choose compounds for development based on a number of factors, including the potential to modulate these circuits. Nerzube is an important example of how we leverage our deep expertise in understanding these receptor systems to discover a novel therapy. Nerzube was made commercially available in mid-December 2023. giving us about 10 days in 2023 where women with PPD in need of treatment could access health care providers. We're excited that we're getting this new treatment option to women who desperately need it. Of course, our work has continued in 2024, and I'm inspired by the stories from our teams in the field in just the first few weeks of launch. Women with PPD and their families now have a treatment option with the potential to make a profound difference in their lives. And the providers with whom we've spoken see Zerzuve as a potential catalyst to increase much-needed screening, diagnosis, and treatment of PPD across the healthcare system. It's early, but I do believe that Zerzuve is the key to unlock the blockbuster potential of PPD, enabling us to help many women suffering from postpartum depression. Importantly, there have been encouraging developments across the treatment landscape. We're starting to see PPD recognized as an urgent medical condition. There's more conversation and dialogue about addressing stigma, and the treatment system is mobilized to better support patients. I want to thank advocates and providers who have prioritized addressing maternal mental health treatment disparities. Turning to the launch progress, Zerzuve has generated $824,000 in collaboration revenue during the fourth quarter of 2023. As a reminder, our reported collaboration revenue is 50% of the net sales by agent records for Zerzuve. As we are very early in launch stages, we're not discussing specific revenue expectations or launch trajectory. However, what I can say today is that we're encouraged by the initial progress we're seeing. Our early initiatives aimed at establishing Zerzuve as the first-line therapy for women with PPD have begun to translate into strong tailwinds for the launch of Zerzuve. Just a few critical highlights. We're hearing that women with PPD are starting to step forward to advocate for Zuzuvay as they discuss treatment options with their healthcare providers. Healthcare providers, including psychiatrists, OB-GYN, primary care, nurse practitioners, and physician assistants are writing prescriptions for Zuzuvay in the treatment of PPD. A specialty distribution network is in place designed to provide a positive experience for patients with convenient home delivery. The Zerzuve4U Patient Assistance Program is helping to support timely access for eligible patients. Of course, as I said, we're early in launch days, and there are aspects of launch we certainly need to optimize, but the initial response and uptake are highly encouraging. Chris and Kimmy will provide additional updates later in the call, and we look forward to sharing more detail on our progress in the coming quarters. While the launch remains our top priority, We're also excited by all that we have ahead of us in 2024, with multiple data readouts expected across our ongoing studies in Dowson-Emdor, also known as Sage 718, as well as Sage 324. We believe in the potential of both molecules to help patients in need and to become significant drivers of long-term value creation as we aim to strengthen our leadership position in brain health. Additionally, we're excited about the continued progress on our early-stage pipeline with Sage 319 and Sage 421. We remain confident in our ability to continue to execute across our pipeline as we head into a catalyst-rich 2024. With that, I'll turn the call over to Chris to provide additional context on the ongoing commercialization of Zerzuve. Chris?
spk17: Thanks, Barry. As Barry mentioned, we've made tremendous progress in these early days of Zerzuve's launch in PPD, and I'm excited to discuss our recent achievements and ongoing initiatives. At SAGE, we share in the urgency to treat PPD. In the U.S., an estimated one in eight women, or approximately 500,000 women, who have a live birth experience symptoms of PPD each year. Data suggests about half of those receive a diagnosis of PPD, and approximately half of those begin treatment. The increasing recognition of PPD as a serious medical condition is a major step forward. However, we still have the collective responsibility to ensure maternal mental health is supported and treated as a core aspect of women's overall health. With the approval and launch of Zerzuve, we believe there is new hope for women with PPD. We also believe the focus on diagnosis, screening, and treating PPD provides an opportunity to make a meaningful impact on mothers, children, and families. And now I'm happy to share some color on what we believe is an encouraging start to the early launch. At the beginning of the year, Barry highlighted our objective in establishing Zerzuve as the first-line therapy for women with PPD. We believe to do so will require delivering broad, equitable, and affordable access for women with PPD, enabling early positive HCP and patient experiences, partnering with communities to improve the focus on maternal mental health, and providing clear education on Zerzuve and PPD to all stakeholders. With that in mind, we are encouraged by the demand we saw in the initial days of the launch. Let me share some metrics we believe are important and reflective of the progress we've seen. As a reminder, we announced commercial availability in mid-December, so the data I'm sharing reflects demand from around 10 days when women with PPD could access HCPs. As of the end of the fourth quarter, there were approximately 120 prescriptions written. With added launch capabilities in both Sage and Biogen sales representatives active in the field, we continue to be encouraged by the increasing number of prescriptions in early 2024. I'd like to note that this is a metric we intend to show in the initial quarters. However, over time, we will likely move away from this metric and focus primarily on shipments and collaboration revenue. In December, we were pleased to see prescriptions written by psychiatrists and importantly, OBGYNs, who prescribed in approximately equal numbers. We also saw a small number of prescriptions written from primary care physicians, and a number of HCPs wrote multiple prescriptions. All of these trends have continued into early 2024. Of the prescriptions written in December, over 70% were shipped in December and early January. Our goal over time is for most women who are prescribed Zirzuve to receive the medication as quickly as possible. We saw many scripts in December take longer to ship than we'd like, which can be anticipated in the initial days of launch and over a holiday period. We expect that as launch progresses, women with PPD will have access to Zirzuve more rapidly, particularly as factors such as payer formulary decisions are made. HCPs and patients become more experienced in using our SP network, and the specialty pharmacy process is further optimized. Moving on, as Barry noted, our patient support program, Zerzuve4U, is activated and working well. In December, the commercially insured patients using the Zerzuve savings card paid no copay expenses. We maintain our commitment to the goal of having Zerzuve be both broadly accessible and affordable for women with BPD. And importantly, on the coverage front, conversations are advancing across national, regional, and government payers, and in the early weeks of the launch, the vast majority of SHIP prescriptions are being covered by payers, even as coverage policies are being developed. We are so far not encountering significant payer headwinds, and to the contrary, we are seeing positive payer engagement. As we said, we expect commercial coverage formulary decisions to continue to come on board in the first half of 2024, with Medicaid stretching into the second half for certain states, as that process typically takes more time. The early demand for Zirzuva is reflective of the strong enthusiasm we're hearing from HCPs and women with PPD for this medication. Further, as we look at who is driving the prescribing, we believe that the strong engagement across specialties and providers represents HCP appreciation for the need to treat PPD as an urgent medical condition, regardless of the practice setting. And notably, these prescriptions are coming from HCPs, many of whom have been reached either through personal promotion or who have engaged with our website digital content, reinforcing the initial impact of our omnichannel efforts. We're still in the early weeks of launch, and we know we have more work to do to help women with PPD access treatment. With that said, we're encouraged by what we're seeing so far. The launch has reaffirmed the unmet need and urgency for a new medication for women living with PPD. and we know we need to continue to execute to maintain this momentum. I look forward to sharing additional details on our Enviogen commercialization efforts in the coming quarters. With that, I will turn it over to Laura for a more detailed discussion of our recent pipeline progress and current clinical expectations. Laura?
spk10: Thanks, Chris, and good morning, everyone. Over 2023, we have made important progress on our pipeline program. And I am pleased to share our recent progress and plans for continued development over the coming quarters. I want to share my excitement to be part of such a significant moment for maternal health with the launch of Zerzuve and the treatment of women with PPD. Not only are we seeing growing interest from HCPs to learn more about Zerzuve, but we believe the launch of Zerzuve is a catalyst for positive change in the screening diagnosis and treatment of PPD. We are seeing increased awareness and attention to PPD in the media and by professional organizations. This has increased knowledge about the cause of PPD and potential treatments and reduced stigma, making it easier for women to seek care. Further, I'm excited to see SIRS-UV being recognized amongst clinicians, and OB-GYNs in particular, as a distinct new treatment option for women with PPD. It has a novel MOA and is a rapidly acting, short-course treatment with a flexible approach that gives HCPs the option to use their Zubay alone or in combination with other therapies. In a short period of time, we believe we are starting to see PPD move from a disease where some HCPs would suspect the diagnosis and refer for evaluation and treatment to a disease that HCPs are confident to diagnose and treat. Supporting mothers has always been a core focus for us, and we are excited we finally have an oral option for HCPs who want to offer more to women with PPD. In addition to the work that we do in PPD, we have many interesting programs in our pipeline. Dalsanemdor, also referred to as SAVE718, is a program that we are really excited about. We are advancing Dalsanemdor, our wholly-owned, first-in-class NMDA receptor positive allosteric modulator, or PAM, as a potential oral therapy for cognitive disorders associated with neurodegenerative diseases, including cognitive impairment in Huntington's disease, or HD, Parkinson's disease, PD, and Alzheimer's disease, AD. Disorders with cognitive impairment represent some of the greatest areas of unmet need in medicine. And we know that globally, they continue to increase in prevalence and pose significant challenges to patients in their everyday lives. The mechanism of action of dalsanemdor is differentiated and leverages our deep understanding of how neuroactive steroids interact with the NMDA receptor. A growing body of evidence suggests that NMDA receptor hypofunction may occur in a wide range of neurodegenerative disorders associated with cognitive impairment, including Huntington's, Parkinson's, and Alzheimer's. is a novel molecule derived from our understanding of the pharmacology of a neuroactive steroid, 24S-hydroxycholesterol, an endogenous NMDA receptor PAM. Balsanemdor is believed to bind to the NMDA receptor with the potential of modulating NMDA receptor activity to improve cognitive function. We are encouraged by the consistent effects on important domains of cognition, such as executive function and learning and memory, that we've seen in our earlier studies in HD, PD, and AD. And we are excited to be progressing a clinical development program for Dalsanemdor with five ongoing clinical trials. Starting with HD, the lead indication for Dalsanemdor, we are currently enrolling in three studies in people with cognitive impairment due to Huntington's. The DIMENSION study is a double-blind, placebo-controlled phase two study designed to evaluate the efficacy of one stale Dalsanemdor dosed over three months. The Surveyor Study is a double-blind, placebo-controlled Phase II study designed to generate evidence linking efficacy signals of cognitive performance to real-world functioning. And the Purview Study is an open-label Phase III safety study of DALS and mDOR designed to evaluate the long-term safety profile and long-term functioning compared to HD natural history studies. As a reminder, The primary objective of the Surveyor Study is to understand the magnitude of the cognitive impairment in Huntington's relative to healthy individuals. A key secondary objective is to advance our understanding of the effects of DELS and mDOR on cognition and function in participants with Huntington's. It's important to note that the Surveyor Study is not designed or powered to show statistically significant differences between DELS and mDOR and placebo. These data are meant to complement the dimension studies by generating evidence to better define clinically meaningful change and the relationship between changes in cognition and function. Moving now to our PD and AD studies for Dalsimandor. The precedent study is a double-blind, placebo-controlled phase two study in people with mild cognitive impairment due to Parkinson's disease designed to evaluate the safety and efficacy of Dalsimandor. The LightWave study is a similarly designed Phase II study to evaluate safety and efficacy of Dalsanemdor in people with mild cognitive impairment and mild dementia due to AD. We expect to announce top-line data from precedent for PD in early 2024, Surveyor for HD in mid-2024, and Dimension for HD and LightWave for AD both in late 2024. We're very excited for these readouts. And if positive, they will help demonstrate a path forward for Dalsanendor and, importantly, bring us one step closer to helping patients. Turning to SAGE324, which is an investigational positive allosteric modulator of GABA-A receptors with significant potential in the treatment of movement disorders like essential tremor. Essential tremor has suffered from a lack of innovation. With no new approved treatments in more than 50 years, and it has a significant impact on an individual's ability to perform everyday tasks. In the U.S., the total annual estimated economic impact of essential tremor is over $100 billion, including medical, loss of employment, and disability costs. We are excited about the potential of Stage 324 in essential tremor, a program that we are developing in collaboration with Biogen. As a reminder, the Kinetic study demonstrated statistically significant reduction from baseline in upper limb tremor amplitude. Kinetic 2 is a three-month study designed to identify a dose with a safety tolerability profile that is suitable for use of SAGE 324 as a chronic treatment in essential tremor. While the primary endpoint for Kinetic 2 is a change from baseline in upper limb tremor amplitude, we will also evaluate a modified version of the Tetris ADL to give us directional insight into the effects of SAGE 324 on quality of life and activities of daily living. We have completed enrollment of Kinetic II and expect to report top line data mid this year. Lastly, I'd like to share our excitement around the earlier SAGE pipeline. In particular, I'd like to highlight two novel molecules, SAGE 319, our extra synaptic GABA-A receptor PAM, and SAGE 421, our NMDA receptor PAM. We look forward to sharing more about these programs as they progress. In closing, I am proud of our pipeline efforts this year, and I look forward to our future progress and clinical execution throughout a catalyst-rich 2024. Now, I'll turn the call over for a review of our financials. Kimmy?
spk08: Thanks, Laura. Our financial results for the fourth quarter and full year 2023 are detailed in our press release issued this morning. Before discussing specifics, I want to share my excitement on the recent launch of Zerjuve and the opportunity to help so many women suffering with TPD. I also want to thank the entire SAGE team for their continued execution and dedication to our mission to support brain health patients. We in Biogen are mobilized with the goal of continued commercial momentum and are jointly supporting the planned launch of Zerjuve with 50-50 cost sharing in the United States. While we're thinking big about the opportunity, we're executing with a focused approach and plan to scale with success. In addition, we are prepared to execute on a catalyst-rich year ahead with multiple expected top-line data readouts for Dalvin Amdor and Stage 324. We're investing strategically in our broader pipeline to have the potential for value creation opportunities for the near, mid, and long-term. I'll now turn to the financials. Today, we announced collaboration revenue from the initial sales of Zerzuve of $824,000. As a reminder, our reporting collaboration revenue is 50% of the net revenue Biogen reports for Zerzuve. Net revenues are recorded when Biogen ships Zerzuve to the distributors and are not based on the number of prescriptions delivered from the specialty pharmacy to patients. Zerzuve net revenues in December 2023 principally represent initial efforts of preparing the channel for the full launch in the first quarter of 2024. Additionally, today we announced milestone revenue of $75 million from Biogen related to the first commercial sale of Zerzuve for the treatment of TPD. We earned the milestone in Q4 and received payment in January 2024. We're not guiding on gross to net today, other than to say, given the fact that Dazuvay is a novel medication and the only approved oral treatment 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 $64.3 million in the fourth quarter of 2023. SG&A expenses were $55.1 million in the fourth quarter of 2023. The decrease in both R&D and SG&A expenses compared to the fourth quarter of last year was primarily related to reorganization cost saving measures such as reduced headcounts, budgeted expenditures, and prioritization of early pipeline programs. We expect that operating expenses will decrease in 2024 relative to 2023. Cost of revenues for Zuzuvie for the fourth quarter of 2023 included one-time charges in preparation for commercial availability. These one-time charges included distribution setup fees and charges for the manufacturing network. We do not expect this gross margin trend to continue. Our net loss for the fourth quarter of 2023 was $32.7 million, and we ended the fourth quarter of 2023 with cash cash equivalents, and marketable securities of approximately $753 million. We are reaffirming that based on our current operating plan, we anticipate cash, cash equivalents, and marketable securities, along with a milestone payment received in January, anticipated funding from ongoing collaborations, and estimated revenues will support operations into 2026. I'd like to note that we have maintained a strong financial foundation as we enter a catalyst-rich year for the company. Before I turn the call over, I want to highlight the scope of our potential as a growing leader in brain health. The launch of Zerzuve demonstrates the culmination of our capabilities, starting from molecule discovery to FDA approval and now commercial launch. We look forward to the year ahead with many exciting catalysts across our pipeline and the continued commercialization of jujube in the treatment of women with PPD. I'll now turn it over to Ashley to handle Q&A with the operator. Ashley?
spk14: Thanks, Kimmy. 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?
spk13: 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 that your mute function is turned off to allow your signal to reach our equipment. Again, you may press star 1 to ask a question. We'll pause for just a moment to allow everyone an opportunity to signal. Our first question comes from Salveen Richter with Goldman Sachs. Please go ahead.
spk15: Great. Thanks. This is Matt on for Salveen. For the 120 scripts, could you share roughly what the split was between commercial and Medicaid and also between treatment-naive and treatment-experienced patients? Thank you.
spk16: Hey, Matt. Thanks for the question. Appreciate it. As we talked about on the call, the December numbers represent about 10 days where moms experiencing symptoms of PPD could access healthcare providers. We can't really provide much more color on the 120 scripts. We're happy with that kind of activity, and we're really excited that the prescriptions came not only from psychiatrists, but from OBGYNs as well as primary care. We don't have all the patient journey data in yet, but we'll certainly provide more color in the quarters to come.
spk13: We'll take our next question from Annapum. Rama with JP Morgan. Please go ahead.
spk03: Hey, guys. Thanks so much for taking the question. Yesterday on the Biogen earnings call, they mentioned, you know, positive payer dynamics. You guys talked about this this morning as well. Maybe you could expand on what you're seeing on the experience to date on the payer side and how we should think about that, you know, sort of first half sort of payer dynamics. Thanks so much.
spk16: Yeah, I'll start, Anna Palm, and turn it over to Chris. And thank you very much for the question. It's really important. So as you heard yesterday from our colleagues at Biage and we've commented on earlier, we're experiencing very positive payer dynamics. The vast majority of prescriptions, this is even before formulary coverage, were paid for, which we highly expected. We've been in PPD for a long time. And the fact that mental health and maternal health are top of minds for payers really provides positive tailwinds. So we're excited by what we're seeing in terms of reimbursement, even before coverage decisions have been made. But Chris, you want to provide more color?
spk17: Yeah. We've historically said that to be truly transformational, you have to be accessible. And we've worked hard over the course of the last several years to really establish the unmet need in PPD and to really share the data associated with Zerzuve, particularly for the treatment of women with PPD. And we've been able to build on that as we progressed into more formal formulary coverage discussions with payers. It's very noted in his opening remarks, we've seen initially before formulary decisions were made, commercial and government insurers, particularly Medicaid, actually paying for prescriptions as they flow through. And we believe this is really reinforcing of what we've already communicated, that there is the potential for Zuzube to be a first-line therapy for women with PPD without the onerous prior authorizations and complex step edits that could challenge that. So we're really excited around the initial conversations that we've had with payers so far.
spk13: Our next question comes from Yasmine Rahimi with Piper Sandler. Please go ahead.
spk21: Hi, this is Jungu. I'm for Yaza Piper. Thanks for taking our question. For 718, what are the key gating factors and bars across studies to warrant further investment? And for essential tremor, given the competitive landscape, what do you need to show to move into phase three in terms of safety and efficacy? Thank you.
spk16: Yes, Jungu. You're talking about SAGE 324. So SAGE 324 is our partnered program with Biogen. Gabapam designed for chronic administration for movement disorders initially studied in essential tremor. I'll start and then Laura can talk about the Kinetic II study. As we saw early, we saw statistically significant reduction in tremor amplitude correlated with activities daily living in Kinetic. What we're looking for in Kinetic II is the optimal dose for chronic administration. Laura, you want to talk more about the competitive landscape and what we're looking for?
spk10: Sure. So we learned a lot from Kinetic-1 in terms of how we designed Kinetic-2. In Kinetic-1, the dose administered was 60 milligrams, and it was administered in the evening. And many patients had sedative effects or sound noise. Before designing the Kinetic-2 study, we took that into consideration and did a number of things. First, we change the administration of the drug to the evening so that the effects of somnolence and sedation would be less problematic. And we also are exploring a variety of doses, 50 milligrams, 30 milligrams, and a titration of 60 milligrams. With that in mind, we feel confident that these data will allow us to identify a dose that has an appropriate risk-benefit profile for a chronic use in eating. With that said, what we're looking for for that dose 4-3-2-4, is a dose that provides efficacy that's similar to or better than agents that are used currently to treat EC with a safety tolerability profile that's appropriate for chronic dosing in this population.
spk16: And do you want to talk about the competitive landscape? There's really been a paucity of innovation in essential tremor. Do you want to talk about what's out there?
spk10: Yeah, it's really incredible. There have not been new products approved in essential tremor for more than 50 years. The last one approved was propranolol. And there have been a number of companies who have ventured into this space recently, all with T-type calcium channel blockers. The data from some of these programs has been negative, and the programs have been stopped. In other cases, the programs are moving forward with JAS and Praxis, and we look forward to seeing their results.
spk13: We'll move to our next question from Ritu Perong with T.D. Cowan. Please go ahead.
spk06: Hi, guys. I wanted to ask about plans for the formal ETV launch as you guys see it. You know, on one hand, there was a huge sort of flurry of news reports, et cetera, around first approval. I understand that there was a commercial or a media outreach campaign around that, and I think there's just a concern amongst investors interested in this program that you might be losing momentum, essentially, as we get further and further out from actual approval and availability and not pushing the button on something like another media push, especially given what you said about patients themselves advocating for access to Sersuve when we found in our own checks that Many OBGYN clinicians are unaware of the drug still, amazingly enough. Can you talk about the rationale for and the status of timing of that real commercial launch? What aspects you can talk about now that'll go into it, you know, why you're waiting, frankly, and... If I could squeak another one in, another question in, just about the free drug program that you have right now for Zirzuve. Thank you.
spk16: Yeah, Ritu, thanks for the question. So, just to be clear, Zirzuve's launched. We received approval in, as you know, in August for PPD. We had DEA scheduling, which took several months, and we invited and made Zirzuve commercially available mid-December. We now, in January, have our full omnichannel up and running and our field force deployed. As you heard us say previously, as Timmy said on the call, we're thinking big about the PPA opportunity, but starting with focus and scaling fast. The media attention has continued, and the sort of anecdotes and stories have continued well, and we're not seeing any slowing at all of momentum. So we're excited by and encouraged by what we're seeing. The patient advocacy groups are certainly encouraged. And as you heard us say, you know, we're beginning to see women with PPD stepping up and advocating. The other important major trends that we're seeing, I'll highlight this, are, you know, PPD is seen as a serious medical condition and not a moral failing. That switch happened relatively fast. The other switch that happened relatively fast, I'm sort of surprised if you've pulled OBGYNs and they're not aware of it. We certainly haven't encountered that. You'd have to sort of be under a rock to not have seen the media attention, which has continued. But the big trend here is that we're seeing some healthcare providers move from the suspicion of depression and the referral to the diagnosis and treatment. And the fact that the prescriptions have come equally from psychs and OBGYN is a good proof point of that trend that we're seeing. You also asked, Chris, do you want to talk about the free drug program?
spk17: Yeah, so let's take a step back and talk about Zerzuve for you, the patient access program that we have in place that's been up and running since the launch of the medication in mid-December, as we've noted. Zerzuve for you has been particularly effective in terms of mitigating patient out-of-pocket, those with commercial insurance down to zero. Everybody that's enrolled in the program has paid zero dollars in order to get Zerzuve, so it's been particularly effective in making sure that Not only is the medication accessible, but it's also affordable. That's particularly key. I think in terms of the free good program, you know, we've got the mechanics in place. If a payer is not particularly going to pay for the medication after a set period of time, we'll actually step in and provide the medication to that patient at no out of pocket. We've seen the vast majority of prescriptions actually be covered prescriptions going forward. We haven't had to actually enact that program significantly. Reflective of, as I said earlier, the support that we've seen from the payer community around making sure that this medication is available and flows through regardless of the fact that patients are either commercial or Medicaid. So we see Zerzuvi for You as a particularly effective program and one that we'll continue to implement in order to make sure all patients have access to the medication.
spk13: We'll move to our next question from Paul Matisse with Stifel. Please go ahead.
spk19: Hi, this is James on for Paul. Thanks for taking our question. Kind of a similar question there around, you know, of those 50, you know, scripts that have actually shipped and been delivered, you know, what percent are actually paid drug? And it sounds like just based on your prior answer, it's the majority. And I guess kind of baked into that, just wondering what you're kind of seeing on a time lag basis from, you know, when a script is written to when it's actually, you know, given to the patient and, You know how you expect to see that evolve over time. Thanks so much Yeah, James.
spk16: Thanks for the question. Let me just take a step back and just clarify kind of the flow So when when we ship drug to a specialty pharma that shipment to the specialty pharma is is the revenue recognition? When a prescriptions written is typically an electronic medical system It's automatically sent to a specialty pharma that counts as a prescription when that specialty pharma then ships the prescription and to the patient's home, that's the shipment. So those are kind of the three key metrics. The vast majority of those shipments were paid for, as we said. We're not providing a specific breakdown, but the vast majority, as Chris already mentioned, it's been paid for not only by commercial, but also by government payers, specifically Medicaid. So we're excited by that. We continue to work on the value proposition here. Obviously, Zuzavay is the first and only oral medication specifically approved for PPD. Its rapid onset of activity is key to the value proposition. So the sooner mom gets drugged, the better off mom is to reattach with family and baby. So we're cognizant of that. We had many shipments that were done in 24 to 40 hours. Of course, some took longer. So that's really an engineering issue. As we optimize the processes, payers come online, and health care providers get comfortable with exactly how to get suzube to moms. Again, highly encouraged in the early days.
spk13: We'll move to our next question from Tazina Mott with Bank of America. Please go ahead.
spk04: Hi, thanks for taking my question. With regards to the prescriber base that you've talked about now for a bit, interest coming in from the OBs, in addition to psychiatrists, but how important is it going to be to penetrate PCPs, and what is your strategy? Can you just remind us of how the sales force is structured? Does a salesperson just target a particular specialty, or are they detailing all three specialties at the same time? Thanks.
spk16: Yeah, Tezeen, thanks for the question. I'll start, and then Chris can provide more colors. So, you know, again, the fact that literally the about 10 days Zirzube was available, in that short period of time, we already saw prescriptions coming in not only from psychs but also OBGYNs in primary care is really indicative of the recognition of PPD as a severe medical condition, not a moral failing, and the awareness that our omni-channel approach and the media had in raising awareness of PPD. Chris, you want to talk about the Salesforce targeting, Omnichannel, and sort of how we're approaching that?
spk17: Yeah, Barry. What I would say first is that what I think we're seeing here is a paradigm shift. Historically, what's happened in the diagnosis and treatment of PPD is clinicians have suspected and then they've referred out. What we're actually seeing here are clinicians, the clinicians that we're calling on, the clinicians that we're reaching through Omnichannel, diagnosing and treating, which is very different than what we've historically seen. In terms of the call universe that we're calling on, we are calling on high prescribing, high volume clinicians with experience in treating postpartum depression. It's a mix of OBGYNs, psychiatrists, and a handful of PCPs that are all a part of that cohort that we're calling on actively with a Salesforce. Obviously we're using Omnichannel to broaden our reach and deepen our frequency because we believe all clinicians who see women with PPD need to hear the messages that we're delivering and have access to the information that enable them to to effectively treat women with PPD as we go forward. In terms of PCPs, what I believe will happen over time is that we'll continue to expand with that first group that we're calling on now broadening to a broader group of PCPs as well as psychs and OBs as we go forward, but that's to come in time as we move forward.
spk13: We'll move to the next question from Brian Abraham with RBC Capital Markets. Please go ahead.
spk23: Hey, good morning. Congrats on all the progress, and thanks for taking my question. Maybe shifting gears to the pipeline, on 718, can you expand on what you're looking for out of the surveyor study in terms of trends and correlations? And I guess I'm curious how that might influence how you would tweak the dimension study, size, endpoints, population, or something else, and whether the goal would be for dimension to potentially be registrational for Huntington's. Thanks.
spk16: Yeah, Brian. Well, first of all, thanks for the congratulations. We really are excited by the progress. And I congratulate you on sneaking five or six questions into your one question. That was good. I'll turn it over to Laura to talk more about it. But before I do, so you talk about Dallas and Amdorf stage 718, which is our fully-owned NMDA-positive allosteric modulator that we're studying in neurodegenerative diseases. And we're excited to have readouts for both Huntington's, Parkinson's, and Alzheimer's this year. Strategically, as we talked about, and Laura will get into specifics, as we've designed the series of Huntington's studies, we've done so recognizing that Huntington's is a rare orphan disease. We've done so in a way that if the data are positive, and let me emphasize, data matter here, that we believe that we have a package to work with regulators on speeding dalsodendor to help those suffering from cognitive disorders in Huntington's. The Parkinson's and Alzheimer's are truly phase two studies where they're learning studies that gives us better support and understanding of designing the phase threes. But you want, Laura, you want to talk more about the dimension in Surveyor studies and how they fit together?
spk10: Sure. So as I mentioned in the introductory remarks, Surveyor is a study that really was designed to serve two purposes. First, to compare the degree of cognitive impairment in patients with Huntington's disease to healthy volunteers. And that's important so that we can understand the clinical meaningfulness of the treatment effect that we see in our studies both for surveyor and dimension. The second purpose of the study was to evaluate how changes in cognition track with changes in function. And this is important to provide supportive evidence both to regulators and to other stakeholders about the relationship between these two metrics. Of course, when we get the surveyor data, we will look at it very carefully. If there are suggestions in that data that there would be a benefit to changing something in the dimension design, we would do that. It's important to note that those changes would be limited to ordering of endpoints, not changes related to adding new endpoints or doing something that would really prolong the study length.
spk13: We'll move to our next question from Ami Sadia with Needham & Company. Please go ahead.
spk05: Hi, this is Purna for AMI. Thank you for taking our question. Just had a question about the bridging program. Could you please talk about it and what type of utilization you're seeing of this program? Should we be expecting use of this program as you complete your peer negotiations?
spk18: Purna, I'm not sure I understand. The bridging program?
spk05: Yes.
spk18: I'm not sure I understand the question.
spk17: Yeah, patient support, I believe. So what we said is there's Zouvet4U is a program that's in place that's largely designed to make sure that we're mitigating patient out-of-pocket. And we talked about that, being able to mitigate the vast majority of these patients that are commercially insured down to a $0 out-of-pocket copay. We also make sure that patients who fundamentally fall in this functionally uninsured group of patients, patients that you would call in other organizations bridge program patients, are actually able to access the medication. So we have that resource in place to actually make sure that those patients don't fall through the system, that they can actually get access to the medication. But as we also said, the vast majority of patients that are flowing through right now are actually covered patients, whether they are commercially insured or Medicaid patients, which again, is a very good sign or signal from payers around the support that they're providing for women with PPP.
spk16: Yeah, and important, keep in mind that, as Chris has mentioned many times, we believe that if a prescription is written for a woman suffering from PPD, that we want to make sure that that woman had drugs. So in our case, it's not really a bridge because it's a 14-day complete course of treatment, not a bridge to a chronic medication.
spk13: We'll move to our next question from Laura Checombe with Wedbush Securities. Please go ahead.
spk22: Hey, good morning, guys. Thanks for the question. I had one on surveyor and dimension and just kind of following up. I was wondering if you could talk a little bit more about the endpoints. And specifically, I'm trying to understand, while you're using the primary endpoint as the Huntington's cognitive assessment battery, I'm trying to better understand how the high-def scale fits in here. And I guess, Laura, based on your comments, could that become a primary endpoint? Thanks.
spk16: Thanks for the question, Laura, on DELS and MDOR. I'll turn it over to Laura to answer.
spk10: Yeah, thank you, Laura. The HC-CAB is the primary endpoint for the dimension study. We have also included the HIDEF measure, which is a measure of function, and it's a patient-reported outcome that SAGE has developed specifically for this population. We have developed and validated that measure, and it would be appropriate to be in an application to support the efficacy profile of SAGE 718 or DELS and MDOR. At this point, we will take what we learned from the surveyor study and make a decision about what the proper endpoints should be for dimension, keeping in mind, of course, that the Huntington's disease cognitive assessment battery is a battery that has been developed by experts in the field to measure domains of cognition that are impacted by Huntington's and actually reflect some of the domains that we believe DELS and MDOR will improve. So we have no reason to believe that that endpoint will not be appropriate or sufficient, but the high def is also a good endpoint that will add additional information about how Dalsanemdor affects patient functioning.
spk16: Yeah, and Laura, it's a really great question. As you're well aware, with Dalsanemdor, we're forging new pathways here. There's not been a medicine specifically approved for cognitive impairment and Huntington's disease. It's a really huge unmet need. And given the orphan nature, again, data matter here, but we believe there'll be tremendous flexibility in working with the package here.
spk13: We'll move to the next question from Nina Betredogar with Deutsche Bank. Please go ahead.
spk07: Hey, guys. Thanks for taking my question. I just wanted to go back to the Zerzube launch. So just looking at some of the third-party script vendors, so specifically IQVIA, it looks like there's a decently high capture rate versus what you've reported in terms of dispensed scripts. So I'm just wondering if you can kind of comment on that and if we should look at those third-party vendors moving forward. And if you can talk at all about what you've been seeing kind of on a week-over-week perspective on scripts so far this quarter, that'd be great too. Thanks.
spk16: Yeah, Nina, let me start. I'll turn it over to Kimmy to talk specifically about IQVIA. So, you know, again, What we've reported out in the fourth quarter was roughly 10 days of commercial availability where moms could access healthcare providers to advocate for Zuzube. We're not really talking about the data specifically in January and February, other than the fact that we're seeing positive trends continue. But Kim, you want to talk more about the Acuvia data?
spk08: Sure. The launch is trackable through Acuvia. However, the data may not provide a complete picture of Zuzube utilization. What you see in the data is shipments to patients, not prescriptions, and the data does lag by about a week. The data, I'd say, is directionally correct, but not precise. There are things like free goods that might not be captured in certain cases, or there might be specialty pharmacies we contract with that might not be covered. So again, I'd say the data is directionally correct, but not precise.
spk13: We'll move to our next question from George Farmer with Scotiabank. Please go ahead.
spk12: Hi, good morning. Thanks for taking my question. Still on the Zerzube scripts, Biogen reported 2 million in sales in December, and you guys are reporting 120 scripts written over the same period, just kind of back of the envelope. Math suggests that all those scripts generated revenue. Is that the right way to think about this? And maybe you can comment on whether there were other scripts that didn't get filled, and how many, you know, perhaps there were some other scripts that were part of the free drug program as well. Is that the right way to think about this?
spk16: Yeah, George, I'll take that, and thank you for the question. So it's important. Let me reiterate sort of the supply chain, if you will. When specialty pharmas stock the drug, they put an order in. When that order is sent to the specialty pharma, That's where revenue comes in. So revenue is drug into specialty pharma. The drug gets pulled from specialty pharma when a healthcare provider, and this is done mostly electronically, writes a script. That script automatically goes to specialty pharma who does insurance verification, other back-end processing. And when all that's done, and it can happen in 24 to 48 hours, that prescription then is shipped to the patients. The IQV data that Kimmy talked about are those shipment data, so that's what you can see. We're providing color on script, which, as Chris mentioned, will provide for the first couple quarters, but likely will drop that metric. So it's not a direct correlation. Now, you know, the fact that we saw 120 scripts is exciting and encouraging in a very short period of time in December.
spk13: We'll move to our next question from Sumant Kulkarni with Canaccord Genuity. Please go ahead.
spk00: Good morning. Thanks for taking my question. Now that you've probably had some patients finish their 14-day course of therapy, what sort of real-world feedback are you getting from patients on how quickly Zerzue may be working in the real world and how patients might be feeling after the treatment, and if there are any unexpected positives or negatives we've seen post-dosing?
spk16: Yeah, Sumant, great question. So the early feedback we've heard from the field is positive, and we're highly encouraged by the anecdotes of the early patient success stories. Of course, you know, a bunch of anecdotes don't add up to data. We're also pleased that we're hearing back from many healthcare providers, including OB-GYNs, primary care, and psychs about Drusuvib. And in general, what we can say is, in the real world, Drusuvib is performing as we saw in clinical trials, and that is taken at night, rapid onset of actions. 50 milligram is being prescribed, and patients are completing the 14-day short-course treatment.
spk18: Thanks. Thank you.
spk13: We'll move to our next question from Akash Tiwari with Jefferies. Please go ahead.
spk11: Hi, this is Phoebe on for Akash. Thank you for taking our question. Biogen mentioned on their Q4 call yesterday that they aren't sure if the initial set of prescriptions represent the bolus, given that Zoserva was approved in August and then only launched in December. So do you feel like demand may be a bit choppy out of the gate, and has there been – or has there been any increased demand in January? Additionally, just wondering why you didn't guide to Zoserva ramps for 2024, and do you plan to guide in later quarters? Thank you.
spk16: Yeah, Phoebe, thanks for the couple questions. start i'll ask chris to comment more and then and then kimmy can talk about guidance so the the tpd is not a warehousing effect type disease we're seeing tremendous demand continue into the early part of 2024 so we can constantly say there's no warehousing here we're seeing demand continue and the numbers you know while encouraging are really small relative to the half a million women a year potentially suffering from ppd so there's a long way to go to help many of these women come Chris, you want to talk about the early launch dynamic, and then maybe Kit can talk about guidance.
spk17: So what we're hearing from clinicians out of the gate, and Barry touched on it in his opening remarks, we're seeing strong, positive performance coming from Zerzuve in and around prescriptions, prescribing patterns, patient support, and coverage. Those are all areas that we've talked about significantly. But again, specifically around physician utilization of the medication, we're seeing balanced prescribing across physician types, OBGYNs and psychiatrists with a core group of PCPs that are also writing this medication as well, too. Those are clinicians that actually have women in front of them that are presenting in the moment with the signs and symptoms of PPD. These are not patients that have been waiting for the medication for a sustained period of time as you might see in other categories. So we really believe here, and as Barry said, that this is a category where there is not warehousing effect, and we're going to continue to make sure that we do all that we can through our sales organization and through our omnichannel efforts, and particularly digital, to provide physicians with the education, the information, and the support to prescribe Zirzuve in the moment when these women come through their offices.
spk16: Yeah, and before Kimmy jumps in with guidance, let me, Phoebe, let me highlight something that Chris said earlier on. We're early in launch, but we've already seen the paradigm shift from a healthcare provider suspecting depression and referring to a healthcare provider diagnosing and treating. We're really in launch, and that's already a paradigm shift we're seeing. among these healthcare providers prescribing. That's highly encouraging.
spk08: On the revenue guidance, to start with, we're pleased about the encouraging early launch of Zerzuve, as you've heard from our call. But we believe we need to take some additional time to better understand the dynamics around the uptake. We plan to communicate additional updates related to the commercial of Zerzuve in due course.
spk13: We'll move to the next question from Yantan Sonega with Guggenheim. Please go ahead.
spk01: Thank you for taking the question. Specifically on the precedent study, so the primary endpoint is the Weschler intelligence scale. Could you help us understand how, like what is the relevance of this scale, number one? What do we see from a placebo perspective for this study? I understand You know, maybe you're not willing to go there and tell us what data you would like to see, but just help us understand how placebo perform on this scale so that we have at least a baseline. Thanks.
spk16: Yeah, thanks for the question on DALS and MDOR and the precedent study. Laura, you want to take that?
spk10: Sure. So with the precedent study, we included the waste for coding as a primary endpoint based on information we had gotten earlier in our development program for DALS and MDOR. As I mentioned earlier, in the DELS and MDOR program, we conducted small probe studies in Alzheimer's, Parkinson's, and Huntington's disease. And in each of those studies, we saw signals of efficacy in cognitive domains of executive function and learning and memory. And the WASTE4 coding was a scale that we used in those early studies to detect that treatment difference. So what we are doing now in the precedent study is using that as a primary endpoint. recognizing, of course, that it is not clear whether that could be the end point. So the study also includes a number of other measures of cognition, including the MOCA and the SCOPA-COG. And so we will be looking at directional effects on those end points to make decisions about moving forward.
spk02: And Laura, if I can add just one thing, I think across all these studies, it's important to recognize that we are looking for an improvement upon baseline not necessarily a slowing of change. And I think that will also factor into how we look at the differences versus placebo.
spk13: We'll move to the next question from Vikram Purit with Morgan Stanley. Please go ahead.
spk25: Hi, good morning. Thanks for taking our question. We had one follow-up on your initial read of prescribing behavior. So I believe you mentioned in your opening remarks that there were certain providers who had written multiple prescriptions for Zirzovay. the first 10 days of the launch. So we were wondering if there are any common characteristics across these providers or their patient bases that stick out to you. And more generally, if this gives you a read on how concentrated or not the prescriber base for Zirzivia could be throughout 2024. Thank you.
spk16: Yeah, thanks for the question. I'll take that. I'll ask Chris to add if there's any additional color. So we're actually seeing broad prescribing across the United States among, as we said, psychiatry, OB-GYNs, and small numbers, but primary care. I don't know that there's trends that are indicative of multiple prescribers other than a prescriber that we assume had a positive experience, sees another patient suffering from PPD, and believes that Zuzuvay is the right drug to reach for. As you know, our goal is for Zuzuvay to be the first-line treatment for women suffering from PPD, and we're excited and encouraged by the early progress to date.
spk13: We'll move to our next question from Mark Goodman with Lear Inc. Please go ahead.
spk24: Yes, good morning. Two questions. First, for 324, can you remind us how long the drug is active, such that taking it at night will still have activity throughout the next day? And then a question just on 718. Can you talk about the rationale for using oxysterol in Parkinson's? I understand that Huntington's patients have low levels, but I didn't understand why it makes sense in Parkinson's. Thanks.
spk16: Yeah, I'll quickly take the Sage 324 question and ask Mike to comment on 718. So the half-life of 324 is sufficient for coverage when taken at night for the next day. We're not worried about that. We believe that the drug effect will last in multiple days, actually. So we're really trying to get to a steady blood serum level that translates to a steady level in the brain. Mike, do you want to talk about SAGE-718?
spk02: Yes. And I think the point when we're thinking about SAGE-718 and its role as a modulator of NMDA receptors is while we gained insight from the endogenous modulator 24S hydroxycholesterol, we've also done quite a bit of work with SAGE-718 and other similar molecules that we've worked on to show that it does not require there to be low levels of 24S for SAGE-718 and similar molecules to work. they work on different ways of impacting NMDA receptor function. So we've been able to show that if you have hypofunction due to a genetic change, a pharmacological change, any way that you have a loss of NMDA receptor function, you can rescue those deficits with molecules such as C8718. So in the context of Parkinson's and Alzheimer's, we believe that there is a strong rationale for NMDA receptor dysfunction, even if the proximal mechanism is not related to oxycerol changes per se. And again, that's why we've designed the 718 program to look at different patient populations where we think that there's an underlying cause of NMDA receptor impairment regardless of the specific mechanism driving that change.
spk13: Thank you. 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.
spk16: Thanks, Taryn, and thanks, everyone, for joining us this morning to review our results from the fourth quarter and full year 2023. As we look ahead to the ongoing launch of Zerzuve and enter a catalyst-rich 2024 with multiple data readouts expected, I'm highly confident that we're making important progress to deliver on our mission to develop and launch life-changing brain health medicines so every person can thrive. Thanks again, everyone, and have a great day.
spk13: This concludes today's call. Thank you again for your participation. You may now disconnect and have a great day.
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