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spk00: And by we're about to begin. Good morning. Welcome to Sage Therapeutics first quarter 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 and 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 Helen Rubenstein, Director of Investor Relations at Sage.
spk24: Good morning, and thank you for joining Sage Therapeutics' first quarter 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 related to today's call, as well as the 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 SAC filings for additional details. We will begin the call with prepared remarks by Barry Green, our Chief Executive Officer, who will provide an overview of our progress during the first quarter of 2023. We will also be joined by Jim Daugherty, our Chief Development Officer, who will review recent progress in development activities across our programs. Our Chief Business Officer, Chris Benecke, will provide an update on our preparations for the potential launch of the rent alone in MDD and PPD. And we will then be joined by Kimmy Eguchi, our Chief Financial Officer, who will review the financial results from the first quarter of 2023. Laura Galt, our Chief Medical Officer, will be available during the Q&A portion of the call. With that, I'll now turn the call over to Barry.
spk07: Thanks, Helen. And thank you, everyone, for joining us this morning. At SAGE, We are driven by our mission to develop brain health medicines that deliver what matters most to patients, so every person can thrive. We do this by acting with urgency and challenging scientific convention to think differently as we work to develop new and effective treatments. This month marks Mental Health Awareness Month, which is an important reminder that the need for innovative brain health medicines has never been greater. Depression is the leading cause of disability for young people and those in their prime working years. And the problem, as we all know, continues to grow. Alarming research published recently by the World Health Organization shows that rates of suicide have increased in the U.S. by more than 40%. Simply put, Mental Health Awareness Month reminds us all that we must do more to challenge these trends. People with depression deserve better. Time is now. for SAGE to lead the way in making a difference for patients. 2023 will be a pivotal year for SAGE and is already off to a strong start. We are laser-focused on preparing for the potential launch of seranolone and believe we're on our way to achieving our vision of transforming the treatment of depression if seranolone is approved. We're also advancing our robust brain health pipeline comprised of several new chemical entity development candidates, that is a result of our product engine. We believe our pipeline holds the potential to help millions of people suffering from brain health disorders and deliver significant long-term value creation. Importantly, our work is backed by a strong financial foundation that we believe puts us in a position to further our pipeline ambitions with the goal of being able to launch new drugs or new indications for years to come. Looking forward, we have many key milestones on the horizon. First, the NDA filing for Zoranilone in MBD and PPD is under review by the FDA with a PDUFA action date of August 5th. Now, as I mentioned during our last earnings call, during this review period, we'll not be making detailed comments on the potential label, FDA interactions, or other related topics for Zoranilone. As we prepare for the potential launch of Zoranilone, We in Biogen are continuing permitted prelaunch commercialization activities. We're actively engaged in discussions with payers and policymakers and collecting key insights from healthcare providers and patient advocates with a goal of providing a model of care that works in the best interest of patients with MDD and PPD. Additionally, our team and collaborators have presented data at several key meetings highlighting the negative impact of depression on patients, their families, and society. These findings provide an important backdrop to our ongoing launch preparation. Chris will provide additional details on our ongoing and planned commercialization activities later in the call. We in Biogen are also advancing SAGE 324, which we believe holds potential to provide differentiated benefits to patients with essential tremor and other movement disorders. Now, turning to neuropsych, we're making progress across our wholly-owned SAGE 718 and MDA PAM programs. With Sage 718, we're leading with Huntington's disease, a devastating condition where deficits in executive function manifest during prime working years. We're also continuing to execute phase two studies with Sage 718 and cognitive impairment due to Parkinson's and Alzheimer's diseases. To close, I'm very pleased with our achievements so far this year and look forward to continued progress in 2023. The time is now to unleash the potential for our science and making meaningful impact on the lives of millions. With that, I'll turn the call over to Jim for a more detailed discussion of our recent portfolio progress and current clinical expectations.
spk09: Jim, over to you. Thanks, Barry, and good morning, everyone. Over the first quarter, we have made important progress on our pipeline program, and I am pleased to detail our recent advancements and our plans for continued execution throughout 2023. I'll start with depression, where we're continuing to prepare for the potential launch of Zoranlone in MDD and PPD. Our vision with Zoranlone, if approved, is to transform the way depression is treated, and we know this will require support from many key stakeholders. Throughout the development journey with Zoranlone, we have engaged with a broad set of key medical experts, including gathering insights from key thought leaders. Their feedback has been clear. They are increasingly recognizing that the episodic nature of depression means it could be treated as needed with treatment-free periods between episodes. Additionally, as we've engaged in discussions about the unmet need in depression, physicians continue to highlight that the potential to achieve both a rapid and sustained effect matters deeply to them and remains critical to their patients. We have received consistent feedback on what they consider the main strengths of the Zaranlone clinical data. A robust clinical development program with approximately 3,500 subjects. Second, rapid onset of action seen in clinical trials with an improvement in depressive symptoms observed as early as day three. Third, improvement in depressive symptoms observed across multiples of round-loan use cases and patient populations in MDD and PPD. Fourth, a consistent safety and tolerability profile. Additionally, physicians note that this clinical profile has the potential to be particularly impactful if Zoranolin is approved, given Zoranolin's 14-day oral course of treatment. We believe that scientific forums will continue to play an important role in educating physicians on the clinical data seen to date with Zoranolin. We are also continuing to highlight data on the substantial economic burden associated with depression. In March, we presented important health economics and outcomes research at the Academy of Managed Care Pharmacy Annual Meeting. These data reinforced the significant negative impacts MDD can have on patients, their families, and society. These presentations highlighted the associations between MDD symptoms and reduced health-related quality of life scores and the burden that extends to other adults living in a home with someone with MDD. They also showed the increase in all health-related and MDD-related costs during the 90-day period following treatment with a current antidepressant. Taken together, we believe these results reinforce the significant unmet need in MDD and PPD and suggest an opportunity for new treatment options that have the potential to improve quality of life and reduce economic burden associated with depression. Combined with additional research our team has presented and published over the last year, these data provide an important backdrop as we continue to engage with payers, policymakers, and patient advocates in pursuit of transforming the way depression is treated. Turning to neuropsychiatry, we announced earlier this quarter that our wholly owned lead NMDA receptor, PAM, stage 718, has been granted orphan drug designation by the EMA which follows the fast track designation granted by the FDA in September 2021, in both cases in Huntington's disease. These designations advance our strategy to prioritize HD as the lead indication for Sage 718, where we are currently enrolling three studies. Population was chosen as the lead indication as it is a genetically defined disorder and thus is more homogeneous than other populations with cognitive impairment. there is a strong scientific rationale to support the use of an NMDA receptor PAM. Given the orphan nature of HD, we believe if our trials are successful, we have the potential to pave a novel regulatory pathway and to seek the globalized stage by pursuing an XUS strategy in a more concentrated orphan space first. We're also continuing research into the HD patient journey. and recently presented interim data at the CHDI annual meeting from 95 patients in a new U.S.-based HD real-world study in collaboration with Picnic Health. This study is examining the impact of HD on patients' activities of daily living, their health-related quality of life, functional independence, and work productivity. The interim data cut demonstrated that patients with HD experienced cognitive impairment across all stages of the disease, impacting their independence and ability to function. Additionally, we are investigating Sage 718 in people with mild cognitive impairment due to Parkinson's disease and people with mild cognitive impairment and mild dementia due to Alzheimer's disease. These disorders represent some of the greatest areas of unmet need, and we know that globally they continue to become more prevalent and significantly disrupt lives. As we said, we expect data from the ongoing studies with SAGE 718 to start reading out in 2024, and we'll share more detailed timelines when appropriate. Our portfolio also includes SAGE 324, our lead neurology candidate. SAGE 324 is an investigational positive allosteric modulator of GABA receptors with significant potential in the treatment of movement disorders like essential tremor. Along with our collaborator Biogen, our goal is to complete enrollment in the ongoing Phase IIb Kinetic II dose-ranging study for SAGE 324 late this year. We are also continuing to advance Phase I studies with a fast-acting balanced Gabapam SAGE 689 and an extra-synaptic preferring Gabapam SAGE 319, as well as IND-enabling studies for our next NMDA PAM SAGE 421. Importantly, all of our product candidates are SAGE-invented new chemical entities with differentiated profiles designed with pharmacologic characteristics that we believe are well-suited to the target indications the program is pursuing. We believe that with our product engine, we have the potential to create significant long-term value if we're successful. 2023 is already off to a strong start, and I look forward to providing continued updates on our clinical execution throughout the remainder of the year. Now, I'll turn the call over to Chris to provide additional context on our planned approach as we prepare for the potential commercialization of Zoran Loan in MDD and PPD.
spk10: Chris? Thanks, Jim. I'm pleased to be with all of you this morning to share updates on our preparations for the potential commercialization of Zoran Loan. With our NDA filing for Zoran Loan in MDD and PPD under agency review, we are closely collaborating with Fireship to advance permitted discussions with payers continuing scientific exchange with HCPs, and engaging with patient advocates. Further, we're building our internal capabilities by hiring experienced commercial leaders whose depth and breadth of knowledge further expand our commercial expertise. Together, these are important steps towards our goal of a rapid and successful launch of Zoranolone. Based on our PDUFA action date of August 5th, if there are no review extensions and if Zoranolone is approved, We expect the potential launch of Zoranilone near the end of 2023, following an anticipated three-month DEA scheduling period. We will be prepared and anticipate entering a market that will be ready to think about the treatment of MDD and PPD differently. Our vision with Zoranilone is to transform the way depression is treated, focusing first on the PPD patient population, An estimated one in eight new mothers in the U.S. experience the symptoms of PPD each year. That's nearly half a million women and their newborn babies and broader families who are adversely impacted during what should be one of the most treasured times for new parents. We believe Zoranolone, if approved, holds unique potential to be a first-line therapy for many of these mothers who need help. Our goal with Zoranalone, if we're successful, is to provide HCPs with the first and only oral treatment specifically indicated for PPD and to improve PPD diagnosis rates. We understand this will require working with the entire healthcare ecosystem to change the diagnosis and treatment paradigm. We believe that if we are able to offer Zoranalone as an oral 14-day treatment option, it may serve as a critical tool and catalyst for HCPs to diagnose, and help mothers suffering from PPD. Based on the compelling and versatile profile seen in the landscape clinical program to date, we believe that Zoranilone, if approved, has high transformative potential as a first-line treatment option for MDD, especially in certain populations like young adults given the 14-day treatment course. We understand that while there is significant unmet need among the entire MDD patient population, we'll need to start our launch in a focused way given payer feedback in the current MDD market dynamics. Therefore, our planned strategy at launch is to focus our efforts on a subset of those 6.5 million patients already diagnosed with MDD who are early in the course of their treatment and in need of a new medication as a first add-on or switch therapy. While many believe that branded entrants to the MDD treatment market are often restricted to much later use, our payer, HCP, government affairs, and patient advocacy discussions all point to the potential for us to help a portion of those six and a half million with a first add-on or switch launch strategy. Further, our launch strategy is designed to scale quickly with success, and we believe that over time, with focus and determination anchored to our data, Zoranolone has the potential to become standard of care in the treatment of MDD. To achieve our vision for Zoranolone in MDD and PPD, if approved, We must execute a fit-for-purpose launch that prioritizes deep and meaningful engagements with key stakeholders. We are advancing planned omnichannel efforts with a digital core designed to unite data from our content, media, and in-person interactions. Our ambition is to strategically increase the impact, efficiency, and agility of our execution through our Salesforce interactions and non-personal promotion. We're powering this approach with predictive analytics, which are intended to deliver customized, personalized information to key stakeholders. It's also vital that our omnichannel work directly reaches people with MDD and PPD at launch. Our planned efforts are intended to directly engage them with education and resources so they're aware of Xeranalone and are prepared to self-advocate in discussions with their HCPs. We believe that if Xeranalone is approved, many people with MDD and PPD, when armed with appropriate education and information, will ask their HCP about it by name. Further, in order to be truly transformational, Zoranilone must be accessible. Our market access team is engaging payers through permitted interactions. To date, we're encouraged by the early enthusiasm we've seen in those interactions. Our goal, if Zoranilone is approved, is to ensure patients with MDD and TPD who are prescribed it can get it with minimal prior authorization and step-edit requirements. As such, we're continuing to explore the use of proactive value-based agreements that we believe may help provide the budget predictability that payers are looking for and favorable access for Xurandalone. We also know that early experience with Xurandalone in the treatment of MDD and PPD will be a driver of a successful launch. Our goal is to enable positive first impressions for both patients with MDD and PPD and providers. To support those positive experiences, if Xoranilone is approved, we plan to provide patient access and support service programs, which we believe will help patients with MDD and PPD navigate their Xoranilone treatment journey. As we continue to prepare for a potential launch later this year, I look forward to sharing additional details on our plans and expectations for the launch of Xoranilone. We're working diligently to deliver a novel treatment option for those living with MDD and PPD, and are highly motivated with a sense of urgency given the real-life impact of depression on people suffering from it and those who love them. We will be ready to execute if Zorana Loan is approved, inspired by our vision for Zorana Loan of transforming the way depression is treated. Now, I'll turn the call over for a review of our financials. Kimmy?
spk18: Thanks, Chris. Our financial results for the first quarter of 2023 are detailed in our press release issued this morning. I'd like to take a moment to provide some context and highlight a few key points. We ended the first quarter with a strong cash position and have made important progress across our pipeline and launch preparation activities so far this year. We have also seen continued growth in the use of Xeratho. I'm proud that since its launch, we've been able to help hundreds of women with PPD with Xeratho. We look forward to potentially expanding treatment options in PPD with Zoranilone if approved. We're executing from a position of strength in a difficult macro environment as we prepare to support the potential commercialization of Zoranolone and invest in development of our robust pipeline. As a reminder, as part of our collaboration with Biogen, we're jointly developing Zoranolone in stage 324 with a 50-50 cost sharing in the United States. We know that to achieve our vision of transforming the care of depression, we must begin with a focused strategy and be prepared to scale quickly with success. And we will remain mindful of capital allocation prior to potential launch. Our net loss for the first quarter of 2023 was $146.8 million, and we ended the quarter with cash, cash equivalents, and marketable securities of approximately $1.1 billion. Turning to operating expenses, R&D expenses were 92.8 million in the first quarter of 2023. The increase compared to the first quarter of last year was primarily related to the hiring of employees and corporate infrastructure costs such as information technology costs to support the growth in our operation. SG&A expenses were 65.7 million in the first quarter of 2023. The increase compared to the first quarter of last year was primarily related to hiring employees to support ongoing activities in anticipation of the potential launch of Durandalon. We're also reaffirming that based on our current operating plan, we anticipate cash, cash equivalents and marketable securities, anticipated funding from ongoing collaborations, and potential revenue will support operations into 2025. Included in this guidance is the potential to achieve milestones totaling $225 million from Biogen related to the first commercial sales of geranolone in MDD and PPD. As we said at the beginning of the year, given how dynamic we expect 2023 to be, including preparing for a potential launch, we're not providing year-end cash guidance at this time. However, looking forward, we expect that our spend will increase as we continue our ongoing and planned commercialization efforts and advance planned and ongoing studies for our brain health pipeline throughout the year. As we approach crucial catalysts, I'm confident that our strong balance sheet will enable us to execute from a position of strength. We have multiple upcoming potential value creating milestones on the horizon. and we're laser-focused on preparing to support the launch of Xerenon, if approved. Backed by a strong balance sheet, we remain committed to making strategic investments in our developing pipeline programs and further establishing ourselves as a leader in brain health. I'll now turn it over to Helen to handle Q&A with the operator. Helen?
spk24: Thanks, Kimmy. Before I turn it over to the operator, I'll ask that you limit yourself to one question. If you have an additional question, please feel free to return to the queue. Now I'll turn it over to the operator to handle Q&A. Operator?
spk00: Thank you. If you'd like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star 1 to ask a question. We'll pause for just a moment to allow everyone an opportunity to signal for questions. We'll take our first question from Anupam Rama with JP Morgan.
spk06: Hey, guys. Thanks so much for taking the question. Just on the mid-year shoreline update for Zorano, can you remind us of what the focus will be here? And will this be presented in conjunction with a medical meeting? I think in your comments, you highlighted that scientific medical forums remain kind of like really important on the medical education front. Thanks so much for taking the question.
spk08: Yeah, thanks for the question. So just on your last point, as collaborators of SAGE and SAGE people continue Science Exchange at Congresses, it's critically important. It's a critical forum for us to share information and get feedback from healthcare providers. And as I know you've noted in some of your notes, the volume of activity and the success of the Science Exchange continues to grow. People are very excited. if approved for Zoraniline to come to market. That's growing and growing. Shoreline's going to be a critical piece of that. What's new, and I'll ask Jim to comment a little bit further in the update, is that we will include the rollover patients from Coral. So I'll remind you that Coral was a Phase III study comparing Zoraniline plus an antidepressant versus an antidepressant, and we saw positive and statistically significant clinical meaningful results differentiating the two at day three. Those patients have an opportunity to rollover to Shoreline, and we're interested in whether the data are the same or slightly different in those arms. But, Tim, you want to take that?
spk09: Of course, and thanks for the question, Anupam. Yeah, absolutely. The shoreline study is a really important part of the overall surrounding program, in part because we get so much information out of it. Of course, we get a fair amount of safety data, given how large the study is. But perhaps even more importantly, it really answers a number of questions around how the surrounding will be used in the real world. And so, as Barry said, what you're seeing is an increasing amount of scientific exchange as we're presenting data from what is a very large study. There are multiple cohorts of patients that have gone through the study. To Barry's point, the last cohort to go through the study are patients that have the opportunity to roll over from the choral study. And what's really interesting there is, of course, the choral study, two arms, one with a standard of care antidepressant and another standard of care antidepressant plus seranolone. Both of those arms have an opportunity to roll into the short-life study. So we really get a good look at subjects who have been on a standard antidepressant and then starting Duranolin for the first time. So we're very interested to see the data. I think you can expect to see continued presentations around the shoreline study for quite some time.
spk13: I think we can take our next question.
spk00: Welcome next to Vituobarrel with P.D. Cowan.
spk03: Good morning, guys. Thanks for taking the question. I wanted to ask on a couple of comments that I heard about the Zoranalone commercial strategy. One, Chris, I believe you mentioned something about a patient access and service program. Is this going to be something like a hub that we see for more specialty diseases with like reimbursement support, paperwork support, diagnostic support? And then just holistically, between your comments and Barry's, it sounds like there might be a DTC element out of the gates with something like this, given you mentioned that you expect patients to ask their doctors or clinicians about this. Is that something that I interpreted correctly? Thanks.
spk08: Yeah, Ritu, thanks for the question. So, as, and I will turn it over to Chris, but as we commented in our planned remarks, We're starting with a very focused approach to zirano-launched and omni-channel, so personal and non-personal promotion, which will include reaching out to potential patients directly. And as Chris said, we plan on scaling fast with success, starting with focus, sort of the think big, start small, scale fast scenario. But specifically to your patient access question, Chris, you want to take that?
spk10: Yeah, thanks, Barry. So good morning, Ritu. Our plan for launch is to make sure that Patients who need Zoranilone are absolutely able to get it regardless of the nature of the patient's payer status. And to that end, what we want to make sure that we do is that for patients at the time of launch, as they have a need for the product, that we provide the appropriate access and reimbursement support services to ensure that when that prescription gets filled, that that prescription actually gets adjudicated and the patient's able to get into the pharmacy for an affordable out-of-pocket. So having a full complement of patient access and support services is going to be absolutely paramount. I think also what's going to be important is for physicians who want to experience the product to have access to not only the ability to prescribe the product, but to provide early experience, essentially a trial program for physicians to make sure that they gain that early experience at launch and are able to use it in the types of patients that they want to use it in. I think in and around your question around DTC and DTP, obviously more to come in and around DTC and DTP. But as Barry mentioned, that there are patients waiting for this medication. We want to make sure that at the time of launch, we're able to provide information and education directly to patients and to those suffering with MDD and PPD and access to tools and resources so that they can engage their clinicians in informed discussions as we go. Obviously, broader DTC is something that we would reserve for later in the launch, but focused DTC and DTP is definitely something that we want to make sure that we're able to offer through omnichannel efforts at the time of launch.
spk03: Great, thank you.
spk08: Thanks, Chris. Just to round that out, Ritu, you can understand that strategically and shoreline data are a good proof point where the majority of people that responded to xeranolone didn't need another medication for over a year. 80% required only the initial or second two-week course. This really is about physicians using xeranolone in their own hands and seeing the impact with their own eyes on their patient population. We believe if the real world is consistent with what we see in clinical trials, that some physicians will have the kind of comments you've heard from people like Greg Mattingly out of St. Louis, things like, I've never seen these kind of reactions before. If that happens out in the real world, and we believe it will, this really is about physicians getting comfortable using Zoran alone for the use to grow.
spk00: We'll go next to Yasmeen Rami with Piper Sandler.
spk02: Good morning, team, and thank you so much for the remarks. I'm going to stick with the topic of commercial preparation. Could you maybe provide a little bit of color on sort of what you're visualizing sort of the size of the commercial team to be? What is the involvement or preparation that BiGen is taking through this process? How should we look at sort of the ramp of bringing in the team throughout, you know, the next 12 to 18 months. Appreciate any color sort of on the execution side of the arm and specifically also what are your partners doing to help you. And I'll jump back into the queue.
spk08: Thank you, Yaz, for the question and your review, Yaz. I really appreciate it. What I can say at this point, I'll kick it over to Chris, is that we and Biogen are highly aligned on the go-to-market plan, the hiring plan, and the kind of think big, start small-scale fast. Chris, you want to take it?
spk10: Yeah, thanks, Barry. So, good morning, Yaz. Our ambition with the Salesforce is to really enable effective reaching frequencies, as you might imagine, on those clinicians who we believe will be new users of antidepressants like seranolone, if approved. The group that we intend to target includes psychiatrists, OBGYNs, a select group of primary care physicians, and nurse practitioners and PAs who are active in this market as well. We'll supplement, as Barry mentioned, our personal promotion efforts with a digital-first on-the-channel effort designed to deepen our reach and to provide frequency on an additional group of physicians who we believe that outside of the call universe that we'll reach with Salesforce need to absolutely hear the message because they have patients who are waiting as well for medication like Zoranilone. We really believe that it's imperative to deliver messaging to Zoranilone on a broad group of these potential prescribers because Patients with depression, as you might imagine, are waiting and deserve better. Now, with respect to the comment about Biogen, as Barry mentioned, we're in lockstep with Biogen around our go-to-market strategy with Zoranolone, inclusive of how we think about deploying sales representatives at the time. Well, obviously, right now, we're thinking about deploying it at the time of effectively the PDUFA date. making sure that we have representatives in the field who are ready to go and are able to optimize the time in between the PDUFA date and the DEA scheduling window so that once the product is approved, post-DEA scheduling, they're ready to go with full promotion. In terms of how we're thinking about moving beyond that, obviously we'll continue to read data, and as the data reads out, we'll think about scaling with success in specific physician groups that we see really, really interest in as we move forward.
spk13: Thank you so much.
spk00: The next is Salveen Richter with Goldman Sachs.
spk12: Hi, this is Salveen. Thank you for using my question. So with regard to the commercialization strategy, could you provide some color on your plans for sampling, as in providing samples to doctors to drive the uptake of the Ranlon during the early months particularly? And if you expect certain restrictions there, given that you expect a DEA scheduling for drug.
spk08: Yeah, thanks for the question. Please send our best to Salveen. You know, as I said, and I'll ask Chris to answer the specific question, but as I said at the beginning, strategically we believe that healthcare provider experience, treating patients with Duranolin and seeing the results with their own eyes is critical to our long-term outcomes. So, you know, as you said, many access opportunities, including sampling, will be a part of that overall strategy. But, Chris, do you want to take it from there?
spk10: Yeah. As a build, Barry, what I'd say is it's important that physicians, as we think about launching the medication, have a clear and compelling use case in mind anchored to the xeranolin data. And they couple that use case with early experiences Barry mentioned so that they get to see the impact that zirinalin can have in the specific patients that they want to use it in. So with respect to how we think about that, we're going to make available, effectively, I think you used the word samples, we would consider it a full-course therapy for a select group of patients, for physicians to actually experience the medication, to see the impact that it can have, because we believe that kind of experience is truly an amplifier to how they think about using it more broadly across their patient populations.
spk13: If we can move on to our next question.
spk00: Next to Jay Olson with Oppenheimer.
spk14: Oh, hey, congrats on the progress and thank you for the update. Can you talk about the impact of the IRA on your development plans for Sage 1A, especially since it's a potential pipeline in a molecule? What is the impact of the IRA on how you plan to develop broad indications, either sequentially or in parallel. And also, if you could comment on the impact of the IRA on your plans for pricings around loans, that would be great. Thank you.
spk08: Yeah, Jay, thanks for the question. So, you know, as we've said before, we think while there are important – positive components of the Inflation Reduction Act, things like smoothing of co-pays and minimizing out-of-pocket for patients and large. It's an act that will not be friendly to innovation. The good news for SAGE, however, is that we have a very robust product engine. So it's too early to share specifics, and with Zoranil and 324, we're partnering with guys, and so I need to completely align with them. But it's safe to say that we believe that innovators like SAGE, whereas we can develop many, many molecules and many indications for molecules, are well-suited to pave the way forward, depending on how IRA is implemented. So what that means is that for Zoranilone, we certainly could increase the use case with other studies like general anxiety disorder or others, or we could take other molecules that differentiate pharmacology to develop them for future indications. And it will be clear as IRA is implemented and we align with Biogen on the long-term use of both seranolone and J324. But great question, Jay. And again, the good news for Sage is that we've got a robust pipeline and a product engine capable of many, many products to come.
spk14: Great. Thanks for taking the question.
spk00: We'll go next to Paul Mateus with Steeple.
spk15: Hey, thanks so much for taking my questions. In your prepared remarks and talking about the commercial strategy, I find it really striking you're talking about positioning Xeran alone as a first add-on antidepressant. I think pretty much any company in depression would love that to be the case, but it just seems to never happen historically. All these new drugs get stuck in the treatment refractory population. So I guess like point blank specifically, how are you actually going to do that? Are you making significant price concessions? Like how's this going to play out? And then I wanted just to ask Barry for just a quick comment on any thoughts. And I don't know exactly what you can say on, you know, where Biogen is at as it relates to psychiatry. They're talking about that as a potential area for business development and They've talked about wanting revenue-generating assets. If they were to in-license a site drug, how might that impact Sage? And I guess how are you kind of thinking about whether or not that's a good or bad thing for your positioning as you launch this product? Thanks so much.
spk08: Yeah, Paul, great question. Let me start with the second question, then I'll talk to the first one and then ask Chris. You really have to advise it about their strategy. What I can tell you from our interactions is that Chris Beebacher has significant experience with depression, given his Glaxo days. On public record, he's very excited about the potential for Zorano to help millions of patients, and very bullish about the revenue consequence of helping millions of patients. So all that's very, very well aligned. In terms of how they grow in business development, that's really a question you'll have to ask a biogen. that a top, top, top priority of Biogen right now is the successful launch of Xeranilone. So we're very well aligned with that. From a stage perspective, as we think about a potential in-licensing, our bar is very, very high. And I can't speak for Biogen, but I expect to hold the bar very high as well. That's certainly how we think about it. In terms of the position with Xeranilone, we commented earlier in the call that strategically, we in Biogen, from the very beginning, aligned on proactive value-based agreements. And what that means is that we're going to work with payers to give them budget predictability, and that's critical. If you think about launches, particularly launches where brands launch into generic areas, often payers, because they don't know how the drug will be used, put significant prior awesome steps in place, really for fear of how rapidly a drug will grow and their inability to budget. we're partnering with the payers to make that more predictable. And what we've heard from payers, and Chris will comment, is that for postpartum depression, since this will be the first, if it's approved, the first oral medicine ever specifically for PPD, that it doesn't make sense for moms to suffer for weeks or months on an unspecifically approved generic for PPD if they can get better in two or three days reconnected with baby. And the long-term health economic consequences of not having a mom connect with baby are severe. And we presented data on this. In terms of MDD, what we're hearing from payers is that in certain use cases, young adults, the elderly, a frontline might make sense. And there's been recent brand launches where about 10 to 15% of the drug is used at frontline. But primarily at launch, we believe that an MDD will be used with patients that are already diagnosed with MDD that are on or have tried something that are not yet satisfied with their level of wellness. Chris, do you want to take it from there?
spk10: Yeah. Thanks, Barry. So, Paul, I've been personally engaged with payers now for the better part of a year and a half. And those conversations initially started around unmet need in the MDD and PPD markets. And we haven't had a payer yet that hasn't acknowledged the unmet need in MDD and PPD. And we progressed through to conversations around the compelling nature of the landscape and nests data and what we saw in our clinical studies. And we've anchored our conversations in and around proactive value-based agreements and the potential impact that those agreements can have with respect to providing payers with predictability and budget certainty that they are so looking for. So between the unmet need and the data from those studies, it's really propelled conversations forward in and around how to think about BBAs and contracting more specifically. And as I mentioned, I've been personally engaged in conversations with national and regional payers inclusive of PBMs for quite some time. And what I can tell you is the byproduct of those discussions is there's significant payer interest in Zoranolone. At launch, we're working to have as many payers lined up as possible to make Zoranolone accessible. And from a medical policy perspective, as you noted, what payers are telling us is there is a clear and compelling use case for Zoranolone in PPD first line. In MDD, what they're telling us is there's a place in the line of therapy as a first add or first switch medication. And while they'll acknowledge that clinicians may want to try something first line before Zorinolone, this is not the kind of medication in MDD that they see being pushed off to third, fourth, or fifth line. Again, that use case is really specific for earlier line of therapy. Now, compare that with Axone's recent launch. What we've seen is restricted coverage. We've seen rejections. And we've seen later line of therapy use. I think there's a number of reasons for that. But given the nature of how Zorinolone works, there's physician interest and urgency to use it. and a payer willingness to recognize the impact that it can have by allowing first line use in PPD and first out of first switch in MDD.
spk13: Awesome. Thank you, guys. Appreciate it. Thanks, Paul. Great question.
spk00: We'll go next to Amy Padilla with Needham.
spk16: Hi. Good morning. This is Ethan Leon for AMI. Thanks for taking our question. Maybe if I can ask one on 324. I guess there's, you know, there's been discussion from another company in the essential tremor space that the Tetris ADL subscale may be the preferred endpoint for regulatory purposes. I believe based on your phase 2B, the primary endpoint is item 4, the performance subscale. So just curious, you know, what do you guys think is ultimately what the FDA wants to see in terms of a registration endpoint? Thank you.
spk08: Yeah, great question. Please send our best to Ami. I'll start and ask Jim to comment further. So for SAFE324, which is a GABA PAM that we developed specifically for chronic use in movement disorders starting with essential tremor, we saw pretty spectacular results in the kinetic study, and that is a statistically significant reduction in tremor scale, as you said, measured by Tetris. We also saw a statistically significant alignment and activities of daily living. So while we haven't had the phase three discussion with FDA on the endpoint, we've got tremendous optionality depending on which way we want the input to go given the data we've seen to date.
spk09: Anyone want to comment? Yeah, I think, Barry, you nailed the key point of what we're seeing from the data are certainly clear results both from the primary endpoint but also to the question that is matched by a similar effect on ADLs. And that's really what you're looking for here is that there is a benefit, a meaningful benefit to patients. And we believe that that is likely to be a key point in the regulators thinking around the little programs here. But look, this all comes out of the process that we've used to identify patient populations who are most likely to benefit from these approaches. And that really did lead us to essential tremor. And so we're seeing substantial reductions in tremor activity from the kinetic warmth study. So we're very excited about the opportunity for modulating the GABA system with, say, 324 as a truly novel way to treat essential trauma.
spk13: All right. Thank you.
spk01: Thank you.
spk00: We'll go next to Sumant Kulkarni with Conaccord.
spk01: Good morning. Thanks for taking my question. Clearly, Xuranolone is a path-breaking product for depression, and you mentioned your preliminary engagement with various stakeholders have been largely positive. but if there's been any pushback or any portions of the value proposition of Ziranlon that require the most effort on convincing, what have those been about, and has that been from experts, payers, or some other source?
spk08: Yeah, Suman, thanks for the question. I'll ask Chris to comment, but what I can say is that temporally, the feedback has gotten more and more positive as the data has been understood, actually on all fronts. I mean, from the very beginning, patient and patient advocates told us there's significant unmet need with depression. Even those that are on antidepressants stably aren't well, they're just numbed. We heard that, you know, two and a half, three years ago from the beginning. I think the big change we've seen from key opinion leaders is that they've moved from a disbelief, there's never been anything new in 35 years other than modeling approaches, how can that be, to a huge belief given the totality of data to the shoreline that, wow, there's a new medicine that works quickly when patients respond as early as two or three days, and the majority only require two weeks of treatment, and they're well. And we've got the SF36 data to support that statement. So I think we've seen a big shift. The pushback historically has been, you know, and how do I know when to retreat? And I think people have understood, and Laura's talked about this extensively, is while this changes the approach to treating depression, it doesn't change the practice of medicine. We're still treating the patients and monitoring them out going forward. From a payer perspective, and Chris highlighted this earlier on the call, is payers all acknowledge the unmet need and realize when talking about the totality of Xeradolin data that we're offering something very, very new in the treatment paradigm. This is not a new entrant that might work a little faster, might offer a little slightly less side effects. This is a completely new approach to depression. So it's not being looked at as the fourth, fifth, sixth, same as launch needs to be pushed to the back line. Laura or Chris, anything to comment? Maybe Laura first. Yeah.
spk23: So I think as a clinician that's treated patients with depression, the thing that really strikes me about the Zaranlo data is the rapidity of the response and the durability of that response. and how it will really change the conversation that you have with patients when you sit down with them and prescribe that initial treatment for depression. Instead of having a conversation about needing to wait for a response for six to eight weeks, needing to be patient, having to sort of power through some of the side effects that might occur early on in treatment, you can have a conversation about expecting to feel well within a few days. And that really is going to change the conversation and the expectations of both physicians and patients.
spk08: Absolutely. And Chris, do you want to comment on the healthcare provider in Parafront?
spk10: Yeah, I think there are three things, Samant, that are going to drive our success from a healthcare provider in Parafront. I think the first is giving physicians or healthcare professionals more broadly a clear and compelling use case that's really anchored to the data. I think Laura hit it nicely around the profile of Zoranolone and why it's desirable for patients that are living with both MDD and PPD. And I think in the remarks, in the slides that we shared, there are a number of use cases in there for patients with unresolved symptoms, patients who may have an adherence or a tolerability challenge, patients who actually may have issues with breakthrough symptoms, and those that are living with elevated anxiety. So again, I think that clear and compelling use case is essential. I think the second thing is to enable early experience where they get to see the power of the medication in their hands, and they get to have the patient's feedback. And I think that's to Barry's point about When we've heard from investigators, the impact that they've seen by virtue of that experience has been really, really meaningful. And lastly, it's working to enable broad unmitigated access without prior authorizations and step edits that are onerous, using proactive EBAs to make sure that payers have the budget predictability and certainty that they're looking for. I think when we do those three things successfully at launch, we're going to have a very successful launch. Thanks.
spk13: Thanks, Iman.
spk00: We'll go next to Vikram Pirohit with Morgan Stanley.
spk17: Hi, thanks. This is for Vikram. Thanks for taking our question. So I want to ask about the scope of lifecycle innovation work you are conducting for the run-alone and what kind of study we can expect and what the data will look like. Thank you.
spk08: Yeah, Vikram, let me turn to Jim to talk more about that.
spk09: Absolutely. Of course, As we're moving forward with seranolone, the goal is to win in depression. And so there are a number of patient populations who we think could benefit from seranolone. I think you begin to think about, given the types of responses we're seeing with seranolone in MPD and PPD, as well as the robust effects we're seeing in those patients on anxiety symptoms, you begin to think about other related anxiety disorders, depressive disorders as potentials. But really, going to specifics is going to require some detailed discussions with our collaborators at Biogen. Those discussions are underway, and so as we get a little bit farther down the road and sort out the sequence of activities that we'll go to, we'll lay those out for you. But I think what we can certainly tell you is that there's a lot of active discussion around which patient populations, in addition to MDD and PPP, we think could benefit from surrounding them.
spk13: Thank you. Thanks, Steve.
spk00: We'll go next to Yatan Sunja with Guggenheim.
spk20: Hi, good morning. This is Eddie on for Yatan. Thanks for taking our question. Just from a high level, when we think about price per patient per year for Zoranilone, should we be thinking about it in terms of treatment courses or some weighted average of patient costs that would include some number of possible retreatments? And then for PPD, should we expect a similar rate of yearly retreatments, and do you have data beyond shoreline to look at PPD retreatments? Thanks.
spk08: Yeah, Eddie, great question. So, we've commented on access before, and, you know, you've heard Chris and me say several times on this call already. It really starts with a proactive value-based agreement, and those provide some risk-taking on our part and some budget predictability and price protection for payers. It's too early to talk about the specifics of value-based agreement, and every payer has a slightly different treat. But the context here is that what we're hearing from payers is that it's important for us to stay below that specialty tier. Since the Sovaldi launch years ago, every payer put automatic mechanisms in place if people are in that specialty tier to put prior ops and steps in place. So please stay below And they're talking about per patient here, not per pill or per pack. And that number is roughly around $10,000 per patient per year. So that's broadly how we're thinking about it. We then cycle that into thinking about the per pack price. Now, it's unlikely that an indication-specific type pricing makes sense here. Will it be a price for the Zoranol and pack of 14 days at 50 milligrams?
spk13: That's how we'll think about price. I'm reaching identity.
spk08: Yeah, you talked about retreating data with PPD. So, you know, right now, what we've seen for the most part is that in both phase three trials that the moms that respond in day three and day 15 hold that response up to day 45. So, we expect that that will hold true in the real world.
spk20: Gotcha. And then just really quickly, I know in the shoreline, there was very few patients that needed multiple retreatments, but is there going to be a maximum number of yearly retreatments allowed, you know, maybe by the payer or from a safety standpoint?
spk08: Yeah, you're cheating. That's two questions. But let me answer that quickly. So, you know, again, we said we're not going to talk about specifics of labels. What you see typically in labels, and we've said this before, is statements about, you know, it's around and studied X amount of times or it's not studied over X amount of times, things like that. We don't think from a payer standpoint. there'll be any kind of restrictions.
spk13: Thank you. Thank you.
spk00: And just as a reminder, please limit yourself to one question. And we'll go next to Brian Abrahams with RBC.
spk19: Hi, this is Leonid on for Brian. Thanks for taking our question. I wanted to ask on you know, some of the recent ended competitor launches and how you're, you know, picking up the learnings from those both on the side of the market, targeting prescribers, potential detailing, and then also maybe just a quick follow-up. Do you have any views on how ziranolone may pair with potentially antipsychotics given the growing role that class is playing in treating MDD and not necessarily just in combination with SSRIs and SNRIs? Thanks.
spk08: Yeah, Leona, thanks for the questions, and please send our best to Brian. So, we are paying close attention to all the new launches, whether it's migraine launches or depression launches, and we are grabbing a whole bunch of learnings from those. You know, frankly, many of what we're seeing in the marketplace were highly predictable given our analytics, but Chris, why don't you take that?
spk10: Yeah, thanks, Barry. As you take a step back and you think about the launches, we pay, as Barry said, very close attention to all facets from the way that they target their customers, the size of the Salesforce, the tools and resources that they're using to effectively manage their launch, all the way through to the external media and how they're spending their media dollars. So we have quite a close lens trained on the various competitors and how they're acting in the market. What I would take a step back and say is that the approval and initial use of other products is really an encouraging signal that both patients and clinicians are really looking for therapies that work. In the case of Axone's product, it's a therapy that they are looking at because it has a new mechanism of action and works a little bit faster than maybe some of the other medications that have historically been available in the market for the last 30 to 35 years. I think this really demonstrates that there's unmet need for new treatment options for the management of MDD. As you know, there still is no treatment, an orally available treatment for PPD. And there is significant need there for a product like Zorinilin. So we anticipate that the opportunity for Zorinilin to be used to manage the episodic treatment of depression is substantial given the novelty of the product, the potential indications that we would anticipate from our data. And we're going to be prepared to go to market to deliver this medication to those living with MDD and PPD as quite a novel product. And we're thinking rather successfully about how we get into the market and launch the product most effectively.
spk13: Great. And the second part of the question on. Yeah.
spk23: So, in regard to your question about use of adrenaline with a typical antipsychotics, I think it's really important to consider the context in which a typical antipsychotics are used in depression. And that is, they're typically used as an add on treatment. when patients have an insufficient response to their standard of care antidepressant, which is usually an SSRI or SNRI. When physicians are in the position of having to treat a patient that hasn't fully responded to that first dose of medication, they don't have a lot of options in their hands right now. And there's not a lot of good data to support many of the options that they might consider. And so they think long and hard before they add an antipsychotic on because of the side effect profile. And so, as a physician myself, when I think about how seranolone is going to be used in the future treatment paradigm, given the efficacy data that we've demonstrated in use, both as mono and add-on, and the side effect profile of seranolone, which is clearly different and has much fewer side effects related to metabolic syndrome and weight gain compared to atypical antipsychotics, it's my belief as a physician that Zoranilone would be used as an add-on ahead of atypical antipsychotics.
spk08: Yeah, Leona, thanks for the question. Or as model therapies. The key that we see in depression, Laura said this as well, is when patients don't respond well, it becomes about polypharmacy. And as you know, polypharmacy in patient populations is continuing to be an issue, particularly as people age and they're on other medications. So the opportunity to use a medication like Zoranilone every night for 14 days is Get well when patients respond and stay well without continued medication, and the chronic therapy is a huge advantage.
spk13: I really appreciate it. Thank you.
spk00: We'll go next to Nina, the Trito Guard with Citi.
spk04: Hey, guys. Thank you for taking my question. Just kind of a follow-up to the last question. Just wondering how you educate, I guess, patients and physicians on the need to actually take the full two-week course. I guess what I'm trying to get at is, you know, is there a risk that patients, you know, take a few days of dosing, you know, kind of get well within that two- to three-day period, and then decide to stop dosing until they need to be retreated again, essentially taking kind of their own treatment into their own hands and treating as needed as they see fit. I guess any thoughts on that will be helpful.
spk08: Yeah, Nina, thanks for the question. I appreciate it. I'll ask Laura to answer that. Yeah.
spk23: So I think that this is a question of educating prescribers and patients on the importance of finishing the 14-day course. That is the treatment course that was studied in clinical trials and supports the efficacy and the benefit that seranolone has demonstrated. So it will really be about making sure that the patient understands the need to finish that 14-day course.
spk13: That's helpful. Thank you. Thanks, Nina.
spk00: We'll go next to Tim Logel with William Blair.
spk22: Thanks for squeezing me in. When you talk about proactive value-based agreements, Chris, I think you mentioned that these were expected to come online at the time of launch. Can you give us kind of a rough idea of how many lives are covered through those agreements or at least expected to be covered at the time of launch? And Is this a process which will be gradual throughout the years of the launch and the lifecycle of the product, or is this something that is looking to be nailed down as early as possible?
spk08: Yeah, Tim, that's a great question. Chris, why don't you take that, and then I'll kind of move back to the end.
spk10: Yeah, what I would say, Tim, is it's early to talk about specific numbers. You know, we're active and engaged with a number of payers right now around proactive value-based agreements and what contracting would look like. I think as you take a step back and think about it, you have to think about it temporarily. There are some payers who I think in and around the time and approval of Zoran alone will be active and engaged around the conversation. I think there are other payer types who may take a little bit of a longer approach. In particular, you think about some of the payer types in and around Medicare may take a little bit longer to take a step back and review the product. We're actively engaged with all of those payers right now and engaged to make sure that as quickly as possible, as those payers are ready to agree to value-based agreements and contracts specifically, that we're going to have the product available in that Perry launch window as rapidly as possible.
spk08: Great answer, Chris. And Tim, just to provide some further context, what I've seen in the past as being involved in value-based agreements is a number of payers who are the more innovative payers get involved earlier, and then other payers see press releases, or other payers talk about it, they will call and say, hey, we need to get involved. Now, the interesting piece here is that everybody you talk to is highly focused on mental health. So we have that as an advantage. Nobody you want to talk to who thinks that depression is solved, and everybody understands that at the end of the day, employers are the customers of payers, and all employers want the people at work all the time. not absenteeism or presenteeism issues, often due to pressures.
spk05: Understood. Thank you.
spk13: Thanks, Jim.
spk00: We'll go next to Mark Goodman with SVB Securities.
spk21: Good morning. On the milestone slide for SAGE 324, it talks about additional data that you're going to be showing this year for ETE. Can you talk about what that data is? And just secondly, are you considering potentially studying that in tremor in Parkinson's disease. We've heard from doctors that that actually could be another population, maybe even an easier population to demonstrate efficacy. Thanks.
spk09: Thanks, Mark. Do you want to take that? Yeah, absolutely. So thanks for the question, Mark. We continue to do analysis on the data that we have from the kinetic study. Remember as well that part of the reason we've moved into this place is that we've done early pilot studies initially with the RASO and then was around the really to identify whether or not this patient population would benefit. So we've got quite a lot of data all throughout the program so far around the benefits of this mechanism in the treatment of essential tremor. And so, you know, those are the data that we're talking about and you'll see those data continue to emerge
spk13: Thank you.
spk00: 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.
spk08: Thanks, Jennifer. And thanks again to everyone for joining us this morning to review our results from the first quarter of 2023. Our progress during the first quarter of 2023 is the result of the teamwork and dedication of everyone at SAGE and our collaborators. As we progress our pipeline development activities, we believe we're well positioned to deliver on our mission to develop and launch life-changing brain health medicine so every person can thrive.
spk13: Thank you again, everyone. Have a great day. Bye.
spk00: This does conclude today's conference. We thank you for your participation.
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