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spk14: Good morning and welcome to Sage Therapeutics Business Update. 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 Kaplewicz. Please go ahead.
spk08: Good morning, and thank you for joining SAGE Therapeutics' conference call to discuss business updates, including the FDA approval of Zoranilone, now branded in the United States as Zirzuve, as a treatment for adults with postpartum depression or PPD. Before we begin, I encourage everyone to go to the investor and media section of our website at sagerx.com, where you can find the press release related to today's call as well as slides that we will be reviewing today. 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. Then, Laura Galt, our Chief Medical Officer, will review the label for Zerzuve and supporting clinical data. Our Chief Business Officer, Chris Bonecki, will highlight our commercial preparations and launch plans for Zerzuve and PPD. And Kimi Noguchi, our Chief Financial Officer, will close with a financial update. Jim Doherty, our Chief Development Officer, will also be available during the Q&A portion of the call. With that, I'll now turn the call over to Barry.
spk17: Thanks, Ashley. And thank you, everyone, for joining us today. This is a historic moment for all women suffering from PPD. On Friday, we and our collaboration partner, Biogen, received approval from the FDA for Zoranolone, now known as Zirzuve, for the treatment of adults with PPD. Zirzuve is the first and only oral treatment specifically indicated for PPD. Hundreds of thousands of women have been waiting and hoping for this moment. We hear so many devastating stories about the impact of PPD, and many of us have been personally touched by this often neglected condition that's estimated to affect approximately 500,000 women each year. Today, there is a new source of hope. Before we begin, I'd like to take a moment to sincerely thank the dedicated healthcare providers, patients, caregivers, and advocates who have made today possible, especially the patients who have placed their immense trust in us throughout our clinical trials. We are and will always be an inspiration for us. We applaud your dedication to seeking new treatment options for PPD. I'd also like to comment on the status of our NDA seeking approval for Zoranilone in the treatment of major depressive disorder, or MDD. As many of you have seen, late on Friday, we received a complete response letter from the FDA for Zoranilone as a treatment for adults with MDD. We are devastated for patients and deeply disappointed with the FDA's position in issuing the CRO. We are reviewing feedback from the FDA and evaluating next steps. As we have clarity, we'll share more. Many have questions that we can't answer and others that we just simply can't at this time. Now, just to be clear, progress in treating depression is not keeping pace with the accelerated prevalence and burden of this debilitating disease. Despite current treatment options, people with depression continue to struggle. A change in the treatment paradigm and approval of novel options is desperately needed. Later in the call, Kimi will provide an update on the financial implications given this development. For those of us that have been in the pharmaceutical industry for decades, going through adversity is an opportunity to come out more lean and agile on the other side. We will work through this. What I can say for now, per se, is that we'll be making smart, disciplined decisions intended to maintain a robust balance sheet. This is an opportunity to merge as a stronger company with a refined strategy and a focused approach. Now, turning back to our primary focus for today's call, following Friday's approval, we have the first and only oral treatment specifically indicated for women with PPD. As a 14-day short-course treatment, we believe that Zirzuve will provide women with PPD a desperately needed new treatment option. with the potential to treat their depressive symptoms quickly without the need for chronic treatment. Given the limited treatment options available for women with TBD, we're excited about the opportunity to bring their Zouvet to those patients. We expect their Zouvet to launch and be commercially available in the fourth quarter of 2023, shortly following the completion of scheduling as a controlled substance by the USDA, which is expected to occur within 90 days of this approval. The widespread national media attention on the approval of Zerzuwe for the treatment of women with PPD reinforces that this is truly a critical milestone given the significant unmet need that currently exists for the treatment of women with this disease. PPD is a serious medical condition. We know that women with PPD often face extreme challenges in their daily lives and with infant bonding, often feeling overwhelmed, anxious, and isolated. If left untreated, Depressive symptoms can persist beyond a year postpartum, which can be associated with prolonged maternal morbidity and mortality. While a woman's PPD can be associated with short-term consequences in newborns, it can also result in long-term developmental, psychological, cognitive, and physical ramifications for her children. The devastating generational impact of PPD has been often overlooked. With the approval of Zerzuve, We now have the first and only oral treatment indicated for women with PPD, and we stand ready to help. I want to take a moment to recognize the entire SAGE and Biogen teams and our collaborators who have brought us to this important day for women with PPD. None of what we do is possible without your hard work, dedication, and faltering belief that together we have the potential to change the mental health landscape. I thank every one of you for your contributions towards our mission. With that, I'll now turn the call over to Laura.
spk09: Thanks, Barry, and good morning, everyone. The approval of SIRS-UV and adults with PPD is a pivotal moment for the women who stand to benefit from this important therapy and a great moment for Sage and Biogen. The approval of SIRS-UV further builds upon the foundation laid with Sage's first approved treatment for PPD and reaffirms our commitment to helping mothers in need. I will start by providing background on SIRS-UV, then I will highlight details of the prescribing information. The mechanism of action of surzube and the treatment of PPD is thought to be related to its positive allosteric modulation of GABA-A receptors, though the mechanism of action is not fully understood. As the primary inhibitory neurotransmitter, GABA immunobutyric acid, or GABA, is widely distributed throughout the brain. It is present in brain regions functionally associated with mood, decision-making, and other behaviors. GABAergic neurotransmission is vital for normal brain function, and evidence shows that GABAergic function may be disrupted in postpartum depression. Now I will summarize the clinical data supporting approval of surzube in women with PPD. The approval is based on data from the NEST Clinical Development Program, which included the Skylark and Robbins studies. These studies were Phase III randomized double-blind placebo-controlled trials that evaluated a 14-day treatment course of Zirzube once daily, used alone or as an adjunct to oral antidepressant therapy in women aged 18 to 45 with PPD. Both studies met the primary endpoint, showing a statistically significant improvement over placebo at day 15 on the 17-item Hamilton Depression Rating Scale. a common measure of depression severity. As shown in the figures, in both the Skylark and Robbins studies, an improvement in depressive symptoms was seen as early as day three and was maintained as day 45, four weeks post-treatment. The potential for rapid onset and the magnitude and durability of effect are all very important to women living with CPD. Now I'll provide an overview of the prescribing information including the safety information. The recommended dosage of Zirzuve is 50 milligrams taken orally once daily in the evening for 14 days with fat-containing food. The dose may be reduced to 40 milligrams once daily if CNS depressant effects occur. Zirzuve can be used alone or as an adjunct to oral antidepressant therapy. Importantly, there are no contraindications in the label. In terms of safety, the box warning states that Zirzube causes driving impairment and patients are advised not to drive or engage in other potentially hazardous activities until at least 12 hours after each dose. Patients should also be advised that they may not be able to assess their own driving competence or the degree of impairment caused by Zirzube. The label also describes the most common adverse reactions that occurred in at least 5% of patients who received sozube and at a higher rate than placebo. These were somnolence, nasopharyngitis, dizziness, fatigue, urinary tract infection, and diarrhea. And finally, while I am personally disappointed that we will not be able to provide a new treatment option to patients living with MBD today as we had hoped, I am also truly excited that we in Biogen will be offering the first oral, rapid-acting, short-course treatment for women with PPD. I can tell you from my clinical experience that we have the potential to help a lot of women with this debilitating condition. With that, I'll turn the call over to Chris. Chris?
spk16: Thanks, Laura. I'm excited to be with all of you to share updates on our preparations for the planned commercial launch of Zirzuve as a treatment for adults with PPD. Today is a day of celebration. The approval of Zerzuve reaffirms our call to action and the urgency that exists to bring this critical new treatment to women suffering with PPD. We know that PPD is all too prevalent in our society and the burdens that it places on new mothers can seem insurmountable. With this in mind, we are incredibly excited about the opportunity to bring a novel treatment option to market that we believe brings us closer to transforming the care of women living with PPD. We have been preparing for a potential launch for many months by advancing permitted pre-approval information exchange with payers, continuing scientific exchange with healthcare providers, and engaging with patient advocacy organizations. Further, we have built an internal team of experienced commercial leaders whose depth and breadth of knowledge and experience further expand our go-to-market capability. We believe our preparations will enable us to be fully ready to execute the launch of ZerzuVe to treat women with PPD by year end. A tremendous opportunity exists in PPD with estimates of approximately one in eight women experiencing PPD symptoms in the US each year. That's about half a million women. Today we know that only about 50% of PPD cases are diagnosed due to inadequate screening. Far too many women with PPD are not getting the care that they need because of the limited options available to them. With the approval of Zerzuve, we believe we have the potential to be a first-line therapy and become the standard of care. Our planned launch focus will be on women diagnosed with PPD requiring treatment. We believe the addressable patient population at launch includes those who are newly diagnosed and those experiencing unresolved symptoms despite taking antidepressant treatment. We're not going to stop there with our efforts to help women with PPD. We believe it will also be important to support efforts to increase diagnosis rates in TPD, building upon the recent guidelines updated by the American College of Obstetricians and Gynecologists, which recommend increased screening during the pre- and postpartum periods. While thinking big about the unmet need in treating women with TPD, we, alongside our collaboration partner Biogen, expect to implement a focused launch strategy that can be scaled with success to reach more women with We plan to leverage our on-the-channel capabilities powered by data and predictive analytics that we expect will enable us to efficiently reach a broad base of healthcare professionals who treat PPD. At launch, we plan to have our focused sales teams targeting high-prescribing psychiatrists, OBGYNs, and PCPs who treat women with PPD with a consistent frequency of promotional messages and resources. Additionally, we plan to advance non-personal promotion efforts with digital platforms designed to reach a broad set of HTPs treating these patients. These digital platforms are intended to unite data from our content, media, and in-person interactions. It's also vital that our omnichannel work directly reaches women with PPD at launch. Our planned efforts are intended to directly engage these women with education and resources so they're aware of Zirzube as a treatment option in PPD and are prepared to have a meaningful discussion about Zirzube with their HCPs. HCPs will be a central focus of this planned on-the-channel approach as they will ultimately be directly responsible for making the decision to prescribe Zirzube in the treatment of women with PPD. We believe early and positive clinical experience and accessibility for women with PPD will be critical to building confidence and accelerating adoption of Zirzuve in this indication. HCP experience with Zirzuve and treating women with PPD will be instrumental to update. We plan to have initiatives at launch in support of this. First, a full-course therapy sample program that will distribute a 14-day short course of therapy to appropriate HCPs to trial Zirzuve in the treatment of women with PPD. We believe this targeted early experience program will be critical to enabling rapid clinical experience with Zirzube that will ultimately drive long-term uptake in this PPD population. The second planned initiative is intended to help enable our goal that every woman with PPD who is prescribed Zirzube can access it, regardless of her financial circumstances. We plan to facilitate this effort through patient access programs at launch, including co-pay assistance for eligible women with PPD who are commercially insured. We intend to discuss our planned commercial strategy, these initiatives, and other planned support for women with PPD closer to the time of launch. We are collaborating across the ecosystem with payers, healthcare providers, patient advocates, and policymakers with the goal of providing a model for care that works in the best interest of patients with PPD. In every state, there is a call to action to prioritize expanding and increasing access to treatment for maternal mental health. There is a need for solutions to address the significant gaps in care. As a new standard of care for women with PPD and a harbinger for change, Zerzuve could improve outcomes for these patients, potentially lessen the overall burden and costs on society, and more importantly, support these mothers and their infants to help them thrive. We believe that a combination of these efforts will help build a positive experience with Zerzuve both for women with PPD and HDPs who treat them. Finally, let's turn to market access. While it's too early to talk about price, here's how we're thinking about it. We plan to implement a PPD access strategy that recognizes the unmet need, considerable economic burden, and the novel clinical profile of Zerzube. We will continue to work with payers with the goal of payroll access and identify ways we might partner, including the potential role of value-based agreements. We've had numerous permitted engagements with payers in the month leading up to PDUFA and payers recognize the significant unmet need for new treatment options in PPD and have been enthusiastic about the clinical profile of Zerzuve in this indication. As we said, our goal is that every woman with PPD who is prescribed Zerzuve can access it, regardless of financial circumstances. As part of our final preparation, Sage and Biogen are currently working to determine adjustments to our thinking on price given the PPD label. We plan to provide more clarity on our overall thinking closer to product launch. What we can say now is that approximately 55% of U.S. births are covered by commercial insurance, and our planned patient access approach for women with PPD were commercially insured as the goal of enabling a vast majority of these women to have access to Zirzuve with minimal out-of-pocket costs. The remaining births receive coverage through Medicaid, which requires little or no financial responsibility for the patient. We expect decisions by payers as to coverage of Zerzuve and the treatment for women with PPD to be made in the months following CEA scheduling. We are prepared and eager to implement this launch strategy that we believe has the potential to maximize the impact of Zerzuve and the treatment of women with PPD by aligning with each of our stakeholders. Through our planned commercialization efforts, we expect to rapidly reach both women with BPD and the HCPs who treat them. Finally, our goal is to enable a favorable access environment so that women with BPD who are prescribed Zirzube are able to get it both rapidly and affordably. We feel this urgency because women with BPD are waiting. I'll now turn it over to Kimmy to provide a financial update. Kimmy?
spk06: Thanks, Chris. And good morning, everyone. I want to share my excitement for this new chapter of Opportunity and Hope for Women with PPD. We're energized to push forward and help so many of these women. And as Barry noted earlier, we are reviewing the feedback from the FDA and the CRL for MDD and evaluating next steps. Given these recent developments, I'd like to briefly comment on what this update means for our financial position. We'll continue to make smart, disciplined decisions as we work to balance cash on hand and revenue generation with our operating expenses. We believe we are well capitalized with $1 billion in cash as of June 30th. And based upon our current estimates, we expect that our cash, cash equivalents, and marketable securities, along with anticipating funding from ongoing collaboration and potential revenue, will support operations into 2025. With that said, Given the update relating to the CRL and MDD, we are refining our strategy. We plan to take action with the goal of extending our cash runway and are currently evaluating resource allocation, including pipeline prioritization and a workforce reorganization. As a result, we also anticipate operating expenses to decrease in 2024. As Barry said, we are working towards a successful launch in PPD, and believe the changes we plan to make will enable us to be a stronger, leaner, and a more focused company. We expect to provide greater detail and next steps before the end of the third quarter as our plans unfold. Before I turn the call over to Ashley for Q&A, I want to reiterate our excitement around this monumental milestone for Stage. We look forward to the commercial availability of the resume later this year, and will act with urgency to help enable women with PPD who are prescribed Zirzuve to have access to it. Let me also add that I know there are many questions out there given the CRL and MDD. As we always have, we'll provide updates when we can. With that, I'll turn the call over to Ashley.
spk08: Thanks, Kimme. Before I turn it over to the operator, 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?
spk14: Thank you. If you would like to ask a question, please signal by pressing star 1 on your telephone keypad. If you're using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Please limit yourself to one question. Again, please press star 1 to ask a question. We'll pause for just a moment. We'll go first to Salvine Richter with Goldman Sachs.
spk11: Good morning. Thanks for taking my question and congratulations on the approval here in PPD. Maybe just to start here with the launch, you talked about the outreach effort with the prescribers. Could you just quantify the prescriber base for us and help us understand the targeted approach and also how a sampling program will work in the context of you know, ensuring you're not soaking up all that initial demand. Thank you.
spk17: Yeah, Salveen, thanks. And thanks for the congratulatory note. We're really excited about the approval of Zerzuve and the treatment of women for PPD. And we're really looking forward to helping these women. We're excited about the opportunity and believe we have a strong business case with kind of the right size organization, the right price. We've got many tailwinds that may help us in launching Zerzuve for the treatment of women. As you noted, it's a big unmet need. About a half a million women in the U.S. experience symptoms each year. The fact that this is the first and only oral treatment approved for women with PPD. And we believe healthcare providers are looking for a tool like this to solve their dilemma on what to do when they diagnose the mom with PPD. And we know that the payers, and I'll ask Chris to comment more about the sample program, are looking forward to a new option for PPD. And certainly, And we mentioned this in the script, that every state and policy, they're implementing policies that we believe will enable access for women at PPD. We can't talk about yet our targeting numbers per se or the size of the sampling program, but maybe Chris can talk about the importance of the full-course treatment and activating healthcare providers to see the results in front of their own eyes.
spk16: Yeah, thanks, Barry. So at launch, we're going to focus our field sales team, as I said in my opening remarks, on high prescribing OBGYN psychiatrists and PCPs. And as you noted, it's going to be really important for that group of physicians to have early experience with Zirzuve. And what that entails is giving them access to a 14-day full-course therapy sample so that they have that experience to see the impact that Zirzuve can have on women living with PPD in their practice.
spk11: Could I just follow up real quickly just to get a sense of quantification of that physician base that you're targeting initially and just help us understand the flexibility you have on pricing and PPD?
spk17: Yeah, so right now, we really can't talk about kind of the size of the physician base. As you're well aware, we and our collaborators, Biogen, have been working wholeheartedly on preparing for a PPD and MDD launch. It has done a lot of work. Of course, We have PPD scenarios that we've laid out, but now the work begins for a PPD-focused launch. As we get closer to launch, we'll come back out with specifics about how we're targeting it. As Chris said in his remarks, we're thinking big about the opportunity, but we're going to start in a very focused way and have clear metrics to scale with success. In terms of pricing, as I said, we think that with the right price and the right size organization, we have a very strong business case, and we're setting about to do that work now.
spk05: Thank you.
spk14: Thank you. We'll go next to Ritu Baral with T.D. Cowan.
spk13: Good morning, guys. Thanks for taking my question. And I'd like to add my congratulations that the drug is available for TPD patients. I would like to focus a little bit on MDD, Barry. I know you can't talk too much about MDD, the interactions and the status, but could you go through at least what happened during the review? Any review issues that were discussed at the mid-cycle review that are now, you know, a focus of unresolved questions? And then what is your expectations of timing for a typing meeting to reach clarity on what else is needed?
spk17: Again, thank you for the congratulatory note. And as you asked, we'll focus on this MDD. So just to be clear, we're extremely disappointed for patients with MDD. We're devastated that we're not able to help them right now. And actually, we do not agree with the FDA's view on Zirzuva for MDD. The mental health crisis is having a devastating impact on our communities, as you know, and we're in desperate need of innovation. So if I back up, You know, we, in accordance with FDA, last year filed our NDA package, and we had started the role in submission earlier in the year with some of the modules. In the clinical section, we had what we believe was six of seven placebo-controlled positive clinical studies in support of that package, which we believe was supportive of both TPD and MDD. We learned late in the review cycle about FDA's view on approvability for MDD. And as we noted, we received the CRL late on Friday. So, you know, the review of the NDA filing package involves an analysis of the submitted information, and we really can't speculate on the FDA's thinking or decision-making. We can simply reflect on what they put in the CRL, which, again, we got late Friday. So, we're reviewing the feedback and evaluating next steps. We're excited to launch through Zubay and PPD as we work with our collaborators at Biogen in understanding what our next steps with FDA on MDDR.
spk13: Do you anticipate interaction even before a Type A meeting?
spk17: I really can't say anything else, Ritu, except that we advise in reviewing the feedback and evaluating the next steps. We've got the right team on it.
spk14: Got it. Thank you.
spk05: Thank you.
spk14: We'll go next to Paul Matisse with Stifel.
spk02: Thanks so much. I guess without being able to talk about the price, which was sort of my first question, I wanted to ask a little bit about the label, because I think there are a few things on there that surprise investors and might have read through under the pipeline. One was commentary around abuse. Another was a commentary on a prior dog study, which seems like it might have been an impediment to chronic administration. And then also restrictions around driving. How do, are those surprising to you that they were on the label, one? And two, do those put into question the profile of SAGE-324, which is being given chronically and has the same mechanism of action? Thank you.
spk17: Hey, Paul, thank you for the question. Let me just start out, and then I'll turn it to Laura to talk about some of the specifics. So, we believe that the label that's provided for for us for the treatment of PPD is a fine label. It's a label that is instructive, it's protective, and it's instructive for healthcare providers and their patients. Certainly a label that allows us to sell their Zouvet for the treatment of PPD for women and a label we can move forward with. So nothing in the label is surprising per se or problematic, but maybe Laura can talk more about that.
spk09: Sure. Thanks for the question, Paul. I'll start first with your question related to driving. So as you see in the label, there is a box warning for driving that instructs prescribers to counsel their patients not to drive for or engage in other potentially hazardous activities until at least 12 hours after each dose is resuvae for the duration of the 14-day treatment course. This recommendation was based on data that's included at the end of the label that summarizes the results of two driving studies that SAGE conducted. I can summarize briefly the results from the 50 milligram dose because that's the most relevant since it's the clinical dose. At the 50 milligram dose, Zozive caused driving impairment after one day of dosing and after seven days of dosing, which was the last time point measured. The label contains very clear instructions for patients. And from our perspective, patient safety has to be top of mind. And it's good that these clear instructions are in the label because it will enable physicians to have good discussions with their patients about the benefit-risk profile of sorzuve. With regard to abuse liability, this is not unexpected for a drug with a mechanism of action like sorzuve. As you can see from what's in the label, there are results from abuse liability studies that show that sorzuve at 30 and 60 milligrams has less abuse potentials than the control, which was the benzodiazepine, but at the 90 milligram dose was approximately equivalent in abuse potential to benzodiazepine. Based on this, we expect that Zuzube will be DEA scheduled, likely scheduled for similar drugs like benzodiazepine. The prescribers who will be prescribing medications for PPD are experienced in prescribing Schedule IV agents, and we don't expect this to be an impediment to use.
spk17: Yeah, let me wrap back with your question about the rest of the pipeline or, you know, GABA PAM. So, as we stated, we intend to complete the Kinetic 2 study for stage 3, 2, 4 at the end of the year. Every new chemical entity has its unique entity, and it's hard to understand if there are any read-throughs in this label or not. Typically, labeling occurs on the basis of data for each individual product.
spk05: So, that's what we can say right now.
spk14: We'll go next to Yasneen Rahimi with Piper Sandler.
spk10: Good morning, team, and thank you so much for hosting this call and taking our question. I know there's a lot that you can tell us about MDD, but could you maybe comment on what are some of the requirements that you would want to maybe not go through in case, like, you know, if there's multiple additional studies required, Is that something that you would want to do? I guess what we're trying to figure out is, like, your commitment to really move this forward and getting this approved. And then the second question for me is just sort of helping us understand how many courses of Ture would be used in patients with PPD, whether you would recommend one or two, and if you could maybe help us understand sort of the use of this product within one year. And I'll jump back into the queue. Thank you.
spk17: Yes, thanks for the question. Let me start with PPD, and I'll circle back. So what we saw in our clinical studies on the profile of Zerzuva was these women that took Zerzuva in the evening with a meal saw rapid response as early as three days, continued response up to day 15. That's clinically relevant and statistically different than placebo, and that effectiveness lasted out to day 45, which is statistical significance to clinical relevance. So with that profile, we envisioned that a mom would take one 14-day course in the course of a year because the trigger event was getting pregnant or having that baby. So I guess the short answer is one. Now, looping back to the CRL, I'll repeat it. We were extremely disappointed for patients, and we don't agree with the FDA's view. They issued the CRL related to NDA for Xeranolone for the treatment of adults And what I can say is what the CRL says, which is the application did not provide substantial evidence of effectiveness to support the approval of xoranolone, the treatment of MDD, and that additional study or studies are needed. We're reviewing the feedback and evaluating next steps, and we really can't comment further other than that.
spk10: Okay. Thank you. Thank you. Thank you so much.
spk05: Thanks, guys.
spk14: We'll go next to Anupam Rama with J.P. Morgan.
spk15: Hey, guys. Thanks so much for taking the question, and congrats on the PPD approval here. Barry, you've mentioned a couple times, you know, the right price in PPD. Maybe you could give us a little bit of color on the bookend to kind of consider, whether it's Volresso or other products. And what are the key considerations to getting to that right price? Thanks so much.
spk17: Yeah, I'll start and I'll turn it over to Chris. And again, thank you very much for the congratulations. Again, we're really excited to help women suffering from PPD. Just to be clear, we can't comment on price or bookends right now. As I mentioned, we did a significant amount of approved pre-commercial payer introduction with the plan to launch NBD and PPD. We had a significant amount of conversations about what the value-based agreements would look like. And frankly, we're prepared for a PPDMVD launch with payers to move forward in contracting. We now have to go back, given the results from Friday and the fact that we got the CRL Friday, and re-engage payers. But we have some basis to do that. Maybe Chris can talk more about that. Yeah, sure.
spk16: Thanks, Barry. We've historically said that to be truly transformational, we must be accessible, Mr. Zubik. We're committed to the goal of rapid and equitable access to Zerzuve for the hundreds of thousands of women who live with PPD. When we think about the approval of Zerzuve and the treatment of women with PPD in the absence of an MDD indication, we'll need to consider the size of the patient population, obviously the strength of the clinical data, including statistical significance at all time points, and the clinical potential of Zerzuve to address significant unmet need for new innovative options in the treatment of postpartum depression. These factors ultimately are what will influence our target wholesale acquisition costs. However, regardless of the WAC, our goal is that every woman, as I said, with PPD is prescribed Zuzube can access it regardless of her financial circumstances.
spk05: Thanks for taking our question. Thanks, Anupam.
spk14: We'll go next to Tazeen Ahmad with Bank of America. Hi, good morning. Thanks for taking my question.
spk07: I just wanted to clarify, did FDA ask you to submit both applications for PPD and MDD at the same time, or was it the preference, or was it SAGE's preference to do it together? Also, you mentioned that, you know, the comments from FDA about the concerns around MDD didn't come until late in the review cycle. Would there have been any opportunity to have an adcom when they brought up the concerns in order to be able to flush it out better? Thanks.
spk17: Yes, several different questions in there. So if I go back historically two and a half, three years, we did, as Sage announced, that we were going to file the NDA for both PPD and MEDs. You might remember at some point it looked like our PPD study was delayed, and at that point we went out and said we were going to file MDD first and PPD after that. And then as the PPD study caught up, we announced that we were going to start a rolling submission and then launch both PPD and MDD at the end of the year. All of that was done in concordance with FDA. In terms of what I can say about the interactions, As you noted, we filed the NDA. The FDA, in February, we announced the FDA gave us a PDUFA date of August 5th and prior to review. And about a month or so later, the FDA told us there was no adcom required, which at the time, obviously, we took as a positive sign. And then just to add to that, we found out late in the review cycle about the FDA's view on the approvability of MDD.
spk05: Other than that, I can't say much more. Okay.
spk14: We'll go next to Brian Abraham. This is RBC Capital Markets.
spk23: Hi. Good morning. My congratulations as well on the approval in PPD. Maybe a question on MDD. do you see a potential for a more narrow or refined indication like the treatment of an acute depressive episode or adjunctive treatment? Is this something that was ever discussed with the agency or potentially on the table? And if this is a possibility, do you think additional studies would be required to support that or not? Thanks.
spk17: Brian, thank you. And thank you very much for a very insightful question. I guess what we can say at this time is We're extremely disappointed for patients, whether it's for the treatment of MDD or a different indication, and we don't agree with the FDA's view. We are evaluating the CRL, and as soon as we can provide more clarity, we will on what the next steps are. We really do believe that Zoranolone should be available to treat patients with MDD, but we've got to get there. And until we're there, we'll be solely focused in marketing for Zuzube to treat women with TPD.
spk05: Thank you.
spk14: We'll go next to Jay Olson with Oppenheimer.
spk21: Oh, hey, thank you for taking the question, and congrats on the PPD approval. We have a financial question. Since you'll be eligible for a $225 million milestone from Biogen, and you'll also experience potentially significant cost savings in the near term without an NDD launch, Are you in a financial position to accelerate the development of SAGE 718? And do you plan to continue that development independently or potentially seek a partnership? Thank you.
spk17: Yeah, Jay. First of all, thanks for the congratulatory note. I'll let Kimmy talk about the milestone and some of our financial thinking. But in terms of SAGE 718, we continue to be really excited by developing CH718 or wholly owned NMDA PAM. The data we've seen to date is exciting in terms of cognitive improvements that we saw in Huntington's, Parkinson's, and Alzheimer's, albeit probe studies and open label studies. As you're well aware, we have a significant number, five well-controlled studies underway right now, several in Huntington's, and then Parkinson's and Alzheimer's. Those should set us up for a very data-rich year next year in terms of stage 718. And as we've commented before, we believe that the Huntington's package is set up in a way that if we see robust data, and given that it's an open indication, you know, we do believe there's some regulatory flexibility, and we'll pursue that flexible approach. Whether it accelerates or not is another question. That's a matter of, you know, clinical studies enrolling and how rapidly they enroll. But we have said previously that we're excited as SAGE alone to launch SAGE 718 in Huntington. Given the nature and the sort of smaller capital footprint that needs, we're excited to do that. Kim, can you talk about, you know, kind of milestones and other financial guidance?
spk06: Sure. Thank you. It's a great question. So just a reminder, earlier I talked about that based on our current estimates, we expect that the cash on hand anticipated funding from collaborations and potential revenue will support our operations into 2025. And we also mentioned that we have the potential to earn a milestone payment of $75 million from Biogen related to the first commercial sale of Dersuve for the treatment of PPE. But to be clear, based on the receipt of the CRL on Friday evening, we are looking forward to and plan to refine our strategy and spend. So that's going to really include an evaluation of our resource allocation. We'll be looking at the pipeline. We'll be looking at a workforce reorganization, and that's all with the goal of extending our cash run with. We expect our evaluation of our resource allocation will incorporate the feedback from the FDA that we have at that point in time. So we expect that we'll be able to update all of you by the end of the third quarter. And we'll certainly talk to you once we have this plan in place.
spk17: And, Jay, just some additional color since you mentioned it. You know, as Chris Bonecki said, you know, we're thinking big about the opportunity to help moms with PPD. It's half a million women. But it certainly starts with a very focused footprint in terms of commercialization, omni-channel, and then we'll have markers that scale that with success. But we're certainly not going to overscale the launch for PPD.
spk05: Great.
spk17: Thank you very much.
spk21: Thanks, Jay.
spk14: We'll go next to Samant Kulkarni with Canaccord.
spk20: Good morning. Thanks for taking my question. How collaborative with Biogen do you expect the Zerzuve launch to be, and do you expect to announce pricing on TPD prior to interacting with the FDA on MDD or after?
spk17: Samant, thank you. Thank you for those questions. So, in terms of Biogen, we and Biogen have been working extraordinarily collaboratively preparing for the potential of an MDD and PPD launch if approved. And they got the label and the approval for PPD Friday night and the CRO for Friday night. And then as you saw, we together issued a joint press release a couple hours later announcing that we plan to launch through Zouvet for PPD and have that launch available in the fourth quarter this year. and shortly after the DEA scheduling, which takes approximately 90 days. So that was a joint collaborative press release. Now with the approval of PPD in front of us and the CRL, we now turn our attention to working towards the appropriate launch of PPD in response to CRL and plan on doing that, as I said, together. In terms of price timing, as we get closer to launch, we will be talking about our access strategy, as well as some of the other aspects of our commercialization. That'll be closer to launch.
spk05: Thank you. Thanks, Vaughn.
spk14: We'll go next to Laura Chica with Wedbush Securities.
spk00: Good morning. Thanks very much for taking the question. I guess just kind of following up on that, I don't know if there's any additional color you can provide on kind of The remainder of 23 in terms of the acceleration on SG&A in terms of PPD launch preparation. And I guess I'm trying to understand kind of the allocation of resources also between you and Biogen. And I guess I'm just trying to understand more broadly. Barry, you had some good comments with respect to how those two partners have interacted over the weekend here. But what is Biogen's commitment to a PPD launch? That would just seem a little bit of a difference than if MDD was involved. Not sure if you can add any color there. Thank you.
spk17: Yeah, Laura, thanks for all those questions in one question. So I guess what I can say is that I can point to the joint press release where we invited and committed that we'd have Zuru Zuru available for PPD in the fourth quarter shortly after DEA scheduling. I can't really talk more about the allocation resource. Yes, as I said, you know, we worked really hard in preparing for the potential of an MDD and PPD launch if approved and had that clearly well mapped. With the news on Friday, the approval of PPD, the CRL for MDD, we're now turning our attention to do the work necessary for what the launch of PPD looks like. And as we get closer to launch, we can talk more about what that looks like. In terms of SG&A or other bills, as Kimmy said, we anticipate Looking at all resources, as well as our workforce, and as I commented earlier, we do believe that even in PPD, with the right price and the right size organization, we've got a really strong business case.
spk14: We'll go to our next caller from Amy Fadia, Needham & Company.
spk03: Hi, good morning. This is Ethan Leon for Omni. Thanks for taking our question. Maybe just kind of on regarding kind of Biogen again, I mean, just I think, you know, just kind of the recent comments that, you know, earnings and the acquisition they announced, it just, I think it's created kind of a perception by some that maybe there could be less committed to MDD. So I, you know, I kind of hear you on the the joint press release and stuff, but maybe, like, how much, I mean, can you give us a sense, just, like, how much commitment do you think, you know, Biogen is, you know, on Seren alone and NDD? And then, you know, with regards to a potential kind of resubmission effort and kind of the, you know, the effort that would be required for that, like, I mean, what role, you know, would you anticipate Biogen kind of playing in that sentence?
spk17: Yeah, again, thank you for the question. I really can't say anything more than we've already said. We're preparing for the launch of Zerzuva and PPD and examining the CRLs. We're reviewing the feedback and evaluating next steps.
spk05: I can't really comment more than that.
spk14: We'll go next to Vickern Perlhiet with Morgan Stanley.
spk12: Hi, this is Steve for Vickern. Thanks for taking our question at Congress on approval. I have a quick question about the PPD. What do you expect the state growth net to be for the roofway, and how long do you think you can get there? Thank you.
spk17: I already talked about the idea that we're going to turn our attention to work on WAC and launch.
spk05: It's too early to talk about gross-to-net. Thank you.
spk14: We'll go next to Mark Goodman with Leverink.
spk04: Yes, good morning. My question is around MDD. In guidance from FDA, they talk about two drug placebo-controlled studies that have to show duration of effect, and you clearly had that in one of your studies, but it's not clear that you had that in a second study, and I was curious if that was the reason that the FDA did not approve the MDT, and if that is the case or whatever the case is, Are you and your partner 100% committed to doing another study in order to do whatever the FDA needs to get MDD? Thanks.
spk17: Thanks for the question, Mark. As I said, we're extremely disappointed for patients with the CRL, and we don't agree with the FDA's views. So that's what I'm going to say right now. All we can say is what we did, which in accordance with the FDA, we filed our NDA last year. what we believe was six of seven positive studies at their edge points and world patrol studies that was our belief set when we filed the nda of course uh and we cannot just say what the cereal states as i've already said which is that the application lasts substantial evidence of effectiveness and that an additional study or studies are required so we intend on evaluating the crl and pursuing next steps in biogen but but but if you need to do another study which the fda is saying are you
spk04: We're going to do another study. We'll do whatever it takes to get NPD, or it's not clear yet?
spk17: So, Mark, let me just repeat. We're disappointed for patients that we don't agree with the FDA.
spk05: We're evaluating the feedback and reviewing next steps. Okay.
spk14: We'll go next to Akash Tiwari with Jefferies.
spk25: Hey, thanks for taking my question, and congrats on the PPD approval. I guess in your collaboration agreement, it mentioned that Biogen could terminate the contract on a product-by-product basis by giving 150 days in advance written notice. Is there a development juncture where Biogen wouldn't be able to terminate the agreement, let's say, for the rent alone? And have you received any notice from Biogen at this point? I just wanted to confirm. Thank you.
spk17: Yeah, Akash. I guess what I can say is there are termination provisions in the agreement. I can also say that, you know, after receiving the PPD approval and the CRL, we jointly worked to issue the press release that you saw committed to launch ZUVE in the fourth quarter for PPD shortly after the DEA scheduling.
spk05: So I'll leave it at that.
spk14: We'll go next to Tim Lugo with William Blair.
spk24: Thanks for the question. Can you walk us through the scheduling process in the next few months It seems like most are viewing it as a formality. However, you know, we've had rises in benzo addiction and abuse in recent years, and sometimes class-wide issues can get wrapped up into single-product discussions. So, can you just help us frame the risk around that process?
spk05: Yeah.
spk17: Thanks for the question, Tim. So, you know, the FDA refers to Zouvet to the DEA for scheduling review. We anticipate that to occur within 90 days. And as you heard Laura say, we expect to have a Class IV label, which is not an issue for prescribers or for patients.
spk24: Great. Thank you.
spk05: Thanks, Tim.
spk14: We'll go next to George Farmer with Scotiabank.
spk22: Hi. Thanks for taking my question. Two things, if I may, real quickly. How long do you think that the sampling program will last as we think about modeling drug penetration in the market? And also, can you speak to your comfort level of risk to feeding newborns, and if you've done any particular studies to address that?
spk17: Yeah, thanks for the question, Jordan. I'm glad for some new questions, and thank you. So, let me start a little bit, and then I'll ask... Chris talked about sampling, and then Laura talked about breastfeeding. So if you take a step back, we believe that healthcare provider experience with Zirzuva in their own hands, seeing the profound and rapid effects that we saw in clinical trials that Zirzuva has the potential to have on moms with PPD is critical to strategy. So physician or healthcare provider activation, and that's where we'll use the sampling program. Chris, you talked about I can't talk to this. We color on use and then we can turn over to Laura for breastfeeding.
spk16: Yeah, so Barry, what I can say is that, as in my prepared remarks, we see this as an early experience program that really focuses on giving physicians that experience in and around the time of launch once we have DEA scheduling. That's a finite window of opportunity for physicians to use that. The actual duration more later as we talk about you know, our actual go-to-market strategy and the details of commercialization. But it is a finite window that we see that in and around the time of launch.
spk17: And what I can add is, you know, we're not talking about all the markers, but, you know, it's likely in our quarterly calls after the launch of the resume for PPD, we'll be providing some color on how many samples are out there and how that's going. Laurie, you want to talk about breastfeeding?
spk09: Sure. Sure. You raised an important question, George, given that this is going to be used in a population that's breastfeeding. SAGE has done a clinical lactation study, and the results of that study showed that there's very low levels of SIRS-B present in human milk. In fact, the calculated maximum relative infant dose for SIRS-B is less than 1%. So what it says in the label then is that a physician and patient should consider the developmental and health benefits of breastfeeding weighed with the potential exposure to Zirzube in the breast milk. It's really important that we have this data in the label. It differentiates this label from other drugs that are used off-label to treat MBD where this data is either absent or the levels present in breast milk are much higher.
spk05: Great. Thanks very much. Thanks, George.
spk14: We'll go next to Uyir with Mizuho.
spk01: Josh, thanks for taking my question. I have two quick ones, if that's okay. So the first one, do you think it's easier now with only PPD indications for you to obtain value base? And second one, could you sort of remind us, in the collaboration with Biogen, are there any fees if the collaboration is terminated Any payments that in either direction you have to pay Biogen or Biogen have to pay you? Thank you.
spk17: Yeah, let me start with the second two. So there certainly are termination provisions in the contract. That's about as far as I can go on that one. And then, you know, again, very insightful. We have, as I mentioned, we have many tailwinds for a PPD-focused launch. It's a large unmet need with about a half a million women in the U.S. experience symptoms each year, only about half of whom are diagnosed per year. So a real big opportunity on improving diagnosis. This will be the first and only oral treatment approved for women with TBD, so that's a big advantage. And then talking to healthcare providers who prescribe, they're anxious to have a product like Zuzuba. The issue they have today, if they can't get access to Zalresso, is that they're The products they use take weeks to work, if at all. And as we know, many patients cycle through many different drugs. And the drugs they use today often come with comorbidities, weight gain, sexual dysfunction, GI impact. So at a prescriber level, let's say an OBGYN level, the course of treatment just doesn't fit into how they're dealing with mom and baby, whereas Resuve could be the solution to that problem. And certainly PEARS have been historically supportive of this education. And as we mentioned, maternal mental health is on everybody's mind. It's been on television almost every night. It's at every state level for policies. And we have now the first world treatment that could be a solution set, at least in PPD, for maternal mental health and the policies that are happening at the statewide level.
spk05: Thank you.
spk14: We'll go next to Yatin Sumeja with Guggenheim.
spk18: Guys, thank you for taking my questions and let me add my congrats on the approval. So just two questions, one clarification and then one follow-up. So with regard to the sampling comment, it is our understanding that a control substance has limitation from a sampling perspective. So could you clarify that would you be able to sample it and also, yeah, just that, And then, you know, with regard to the commercial bill, I understand, you know, you provide us more detail once you launch. But let's say if you got approved for MDD and that requires 100 sales wrap, like just trying to understand the commercial bill that on PPD, is it 20 sales wrap, 30 sales wrap, so 20% less, just some sort of ballpark, just trying to gauge what the spend will be also as we model it. Thank you.
spk17: Yeah, let me quickly answer both questions. I know we're getting to the top of the hour. So, you know, what we said about the commercial bill is that we're thinking big, but starting with a very focused way. Clearly, much more focused in PPE than it is in PPE and MDD, but we really can't provide numbers. We also heard from Kimmy that we're prioritizing our pipeline and kind of when we'll resize the organization appropriate for this opportunity in the pipeline in front of us. So, you know, we'll communicate that. in the next month or so. In terms of sampling, there are certain limitations on controlled substance estates, whether you can use an actual sample or a voucher, but we don't see that being a limitation to the concept on the sampling program.
spk14: This does conclude the question and answer portion of today's call. I would like to turn the presentation back over to Barry Green.
spk17: Thank you, Ruth, and thanks again to everyone for joining us today. This is a special day for Sage, Biogen, and all the women with TPD who stand to benefit from Zirzuve. We appreciate the continued support of all stakeholders, and we look forward to providing more updates in the coming months. Thanks again, everyone, and have a great day.
spk14: Goodbye. This does conclude today's call. You may now disconnect.
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