Q4 2023 Sage Therapeutics Inc Earnings Call

Operator: Good morning. Welcome to SAGE Therapeutics' fourth quarter and full year 2023 Financial Results Conference call. Currently, all participants are in a listen-only mode.

Good morning, welcome to stage Therapeutics fourth quarter and full year 2023 financial results Conference call.

Currently all participants are in a listen only mode.

Operator: This call is being webcast live on the Investors & 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.

This call is being webcast live on the investors and media section of sages website at Sage Rx Dotcom.

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.

Ashley Kaplowitz: I would now like to introduce Ashley Kaplowitz, Executive Director of Investor Relations and Capital Markets at SAGE. Good morning, and thank you for joining SAGE Therapeutics' fourth quarter and full year 2023 financial results conference call. Before we begin, I encourage everyone to go to the investors and media section of our website at sageRx.com, where you can find the press release and slides related to today's call. I would like to point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

I would now like to introduce Ashley Kaplowitz executive director of Investor Relations and capital markets at Sage.

Ashley Kaplowitz: Good morning, and thank you for joining Sage therapeutics fourth quarter and full year 2023 financial results Conference call.

Ashley Kaplowitz: Before we begin I encourage everyone to go to the investors and media section of our website at <unk> Dot Com, where you can find the press release and slides related to today's call.

I would like to point out that we will be making forward looking statements, which are based on our current expectations and beliefs.

Ashley Kaplowitz: These statements are subject to certain risks and uncertainties and our actual results may differ materially.

Ashley Kaplowitz: 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 Greene, our Chief Executive Officer, who will provide an overview of our progress during the fourth quarter and full year 2020. Our Chief Business Officer, Chris Bunecki, will provide an update on the ongoing commercialization of Zerzube. We will also be joined by Laura Galt, our Chief Medical Officer, who will review recent progress in development activities across our program. We will then be joined by Kimi Iguchi, our Chief Financial Officer, who will review the financial results for the fourth quarter and full year 2020. Mike Quirk, our Chief Scientific Officer, will be available for questions during the Q&A portion of the call. With that, I'll now turn the call over to Barry.

Ashley Kaplowitz: Please review the risk factors discussed in today's press release and in our SEC filings for additional detail.

Ashley Kaplowitz: We will begin the call with prepared remarks by Barry Greene, Our Chief Executive Officer, who will provide an overview of our progress during the fourth quarter and full year 2023.

Ashley Kaplowitz: Our Chief business Officer, Christopher Lucky, we'll provide an update on the ongoing commercialization of their zubaie we.

Christopher Lucky: We will also be joined by Laura Golf, Our Chief Medical Officer, who will review recent progress in development activities across our programs.

Christopher Lucky: He will then be joined by Camille Gucci, Our Chief Financial Officer, who will review the financial results from the fourth quarter and full year 2023.

Christopher Lucky: Mike <unk>, our Chief Scientific officer will be available for questions. During the Q&A portion of the call.

Christopher Lucky: With that I'll now turn the call over to Barry.

Barry E. Greene: Thanks, Ashley, and thank you, everyone, for joining us. 2023 was a pivotal year for SAGE. Highlighted by the approval and commercial availability of our second FDA-approved product, Zerzube, the first and only oral treatment approved specifically for adults with postpartum depression or PPP. We have a big year ahead of us and even greater potential to build a leadership position in brain health and a top tier biopharmaceutical company. Our reach and expertise across various brain health conditions are key to our work to unlock potential breakthroughs to help patients suffering from Brain health diseases are one of the leading causes of disability worldwide, yet novel treatment options in care remain unknown.

Barry E. Greene: Thanks, Ashley and thank you everyone for joining us and for 2023 was a pivotal year for sage highlighted by the approval.

Barry E. Greene: The ability of our second FDA approved product.

Barry E. Greene: The first and only oral treatment approved specifically for adults with postpartum depression or PPD.

Barry E. Greene: A good year ahead of us and even greater potential to build a leadership position in Brazil, and a top tier biopharmaceutical company.

Barry E. Greene: Rich and expertise across various springhill conditions are key to our work to unlock potential brokers tell a patient suffering from a wide range of brain diseases.

Greenhill diseases are one of the leading cause of disability worldwide novel treatment option.

Barry E. Greene: There remain limited.

Barry E. Greene: We are seeking to change that with a pipeline designed to address brain health disorders and improve public health. Brain health is fundamental to well-being and function at each stage. Through pioneering science, we aim to advance programs that have the potential to improve the lives of individuals living with brain health disorders and their Starting with compounds that selectively modulate GABA and NMDA receptors, our expertise in neuroactive steroids includes oxysterol chemistry, allowing us to choose compounds for development based on a number of factors, including the potential to modulate these circuits.

Barry E. Greene: We're seeking to change that with the pipeline designed to just brain health disorders and improved public health.

Barry E. Greene: Greenhill is fundamental to wellbeing and function at each stage of life.

Barry E. Greene: We're pioneering science, we aim to advance programs that has the potential to improve the lives of individuals living with brain health disorders and their families.

Barry E. Greene: We're focused on modulating grain network function disrupting circuits underlying factor in any brain health disorders Sardinia.

Barry E. Greene: BRD compounds that selectively modulate Gaba and NMDA receptor activity our expertise in Europe with steroids includes oxy still country, allowing us to call films to development based on a number of factors, including the potential to modulate these circuits.

Barry E. Greene: Resurveying is an important example of how we leverage our deep expertise in understanding the receptive system to discover novel treatments. Your Zubay was made commercially available in mid-December 2020, giving us about 10 days in 2020 where women with TPD in need of treatment could access healthcare. We're excited that we're getting this new treatment option to women who desperately need it. And, of course, our work has continued in 2024, and I'm inspired by the stories from our teams in the field in just the first few weeks of the year. Women with TPD and their families now have a treatment that has the potential to make a profound difference.

Barry E. Greene: <unk> is an important example of how we leverage our deep expertise in understanding through two separate systems discover a novel therapy.

Barry E. Greene: <unk> was named commercially available in mid December 2023, giving us about 10 days in 2023 women with PPD in need of treatment good access to health care providers.

Barry E. Greene: We're excited that we're getting this new treatment option to women who desperately needed.

Barry E. Greene: Of course, our work has continued in 2024.

Barry E. Greene: Fiery by the stories from our teams in the field and just the first few weeks of launch.

Barry E. Greene: Women with PPD and their families now have a treatment option with the potential to make a profound difference in their lives.

Barry E. Greene: And the providers with whom we've spoken see Zerhoove as a potential catalyst to create much needed screening, diagnosis, and treatment for people across healthcare. It's early, but I do believe that Suzuve is the key to unlock the blockbuster potential of PPD, enabling us to help many women suffering from postpartum depression. Importantly, there have been encouraging developments in treatment. We're starting to see PPD recognized as an urgent medical condition. There's more conversation and dialogue about addressing stigma, and the treatment system is mobilized to better support patients. I want to thank advocates and providers who have prioritized addressing maternal mental health treatment. Turning to the launch progress, Zerzuvia has generated $824,000 in collaboration revenue during the fourth quarter. As a reminder, our reported collaboration revenue is 50% of the net sales by agent records for the year.

Barry E. Greene: And the providers with whom we've spoken Caesar, who they as a potential catalyst to increase much needed screening diagnosis and treatment of PPD across the health care system.

Speaker Change: It's early but I do believe that <unk> is the key to unlock the blockbuster potential of PPD, enabling us to help many women suffering from postpartum depression.

Speaker Change: Importantly, there have been encouraging developments across the treatment landscape, we're starting to see PPD recognized as an urgent medical condition.

Speaker Change: More conversation and dialogue about addressing stigma and treatment systems mobile is to better support patients.

Speaker Change: I want to thank advocates and providing sort of prioritize addressing material mental health treatment disparities.

Speaker Change: Turning to the watch progress Susie has generated $824000 in collaboration revenue during the fourth quarter of 2023.

Speaker Change: As a reminder, our reported collaboration revenue 60% of the net sales record.

Speaker Change: A record for <unk>.

Barry E. Greene: As we are very early in the launch stages, we're not discussing specific revenue expectations or launch trajectory today. However, what I can say today is that we're encouraged by the initial progress. Our early initiatives aimed at establishing Zerzube as a first-line therapy for women with PPD have begun to translate into strong ties for the launch of Zerzube. Just a few critical highlights.

Speaker Change: As we are very early in launch stages were not discussing specific revenue expectations our launch trajectory.

Speaker Change: What I can say today is that we're encouraged by the initial progress we're seeing.

Speaker Change: Our early initiatives aimed at establishing <unk> as the first line therapy for women with PPD have begun to translate into strong tailwind for the launch of usually the gist.

Speaker Change: Just a few critical highlights we're hearing that women with PPD are starting to step forward to advocate, presumably as they discuss treatment options with their health care providers.

Barry E. Greene: We're hearing that women with TBD are starting to step forward to advocate for Juzuri as they discuss treatment options with their health care provider. Health care providers, including psychiatrists, OB-GYN, primary care, nurse practitioners, and physician assistants, are writing prescriptions for Zuzuvi in a treatment. The Special Needs Distribution Network is in place designed to provide a positive experience for patients. Convenient Home.

Speaker Change: Health care providers, including psychiatrists will be Julien primary care nurse practitioners and physician assistance are writing prescriptions for <unk> in the treatment of PPD.

Speaker Change: Especially the distribution network is in place designed to provide a positive experience for patients with convenient home delivery.

Barry E. Greene: The Zerzube for Youth Patient Assistance Program is helping to support timely access for the elderly. Of course, as I said, we're early in launch days, and there are aspects of launch we certainly need to optimize, but the initial response and uptake are very high. Kristen Kinney will provide additional updates later in the call, and we look forward to sharing more detail on our progress. While the launch remains our top priority, we're also excited by all that we have ahead of us in 2024, with multiple data readouts expected across our ongoing studies in Dalzin-MDOR, also known as SAGE 718, as well as SAGE 321, SAGE 322, and SAGE 323. We believe in the potential of both molecules to help patients in need and to become significant drivers of long-term value creation. We aim to strengthen our leadership position.

Is there a loser for use patient assistance program is helping to support timely access for eligible patients.

Speaker Change: Of course as I said, we're early in launch phase and there are aspects of launch we certainly need to optimize but the initial response and uptake are highly encouraging Christopher.

Speaker Change: Christie Kelly will provide additional updates later in the call and we look forward to sharing more detail on our progress in the coming quarters.

Speaker Change: While the launch remains our top priority. We're also excited by all that we have ahead of us in 2024 with multiple data readouts expected across our ongoing studies in <unk> also known as <unk> as well as saves through two four.

Speaker Change: We believe in the potential both molecules to help patients in need and to become significant drivers of long term value creation as the infrastructure and our leadership position and Bruno.

Barry E. Greene: Additionally, we're excited about the continued progress on our early stage pipeline with SAGE 319 and SAGE 421. We remain confident in our ability to continue to execute across our pipeline, heading into a catalyst route. With that, I'll turn the call over to Chris to provide additional context on the ongoing commercialization of Zerzubeg.

Speaker Change: Additionally, we're excited about the continued progress on our early stage pipeline with <unk> nine and <unk> 41.

Speaker Change: We remain confident in our ability to continue to execute across our pipeline.

We head into a catalyst rich 2024.

Speaker Change: With that I'll turn the call over to Chris to provide additional context on the ongoing commercialization of <unk>.

Speaker Change: Chris.

Chris Bunecki: Thanks, Barry. As Barry mentioned, we've made tremendous progress in these early days of Zerzouve's launch in PT, and I'm excited to discuss our recent achievements and ongoing initiatives. At SAGE, we share in the urgency to treat PPD. In the U.S., an estimated 1 in 8 women, or approximately 500,000 women, who have a live birth experience symptoms of PPD each year.

Chris: Thanks, Barry as Barry mentioned, we've made tremendous progress in these early days of <unk> launch in PPD and I'm excited to discuss our recent achievements and ongoing initiatives.

Chris: Sage, we share the urgency to treat PPD.

Chris: In the U S. An estimated one in eight women or approximately 500000 women, who have a live birth experienced symptoms of PPD each year.

Chris Bunecki: Data suggest about half of those receive a diagnosis of PPD, and approximately half of those begin treatment. The increasing recognition of PPD as a serious medical condition is a major step forward. However, we still have a collective responsibility to ensure maternal mental health is supported and treated as a core aspect of women's overall health.

Chris: Data suggest about half of those receive a diagnosis of PPD and approximately half of those begin treatment.

Chris: The increasing recognition of PPD is a serious medical condition is a major step forward.

Chris: We still have the collective responsibility to ensure maternal mental health is supported and treated as a core aspect of women's overall health.

Chris Bunecki: With the approval and launch of Zerzuve, we believe there is new hope for women with PPD. We also believe the focus on diagnosis, screening, and treatment of PPD provides an opportunity to make a meaningful impact on mothers, children, and families. And now I'm happy to share some color on what we believe is an encouraging start to the early, At the beginning of the year, Barry highlighted our objective of establishing Zerzuve as the first-line therapy for women with PPD. We believe to do so will require delivering broad, equitable, and affordable access for women with PPD, enabling early positive HCP and patient experiences, partnering with communities to improve the focus on maternal mental health, and providing clear With that in mind, we are encouraged by the demand we saw in the initial days of the launch.

Chris: With the approval and launch of <unk>. We believe there is new hope for women with PPD.

Chris: We also believe that focus on diagnosis screening and treating PPD provides an opportunity to make a meaningful impact on mothers children and families.

Chris: And now I'm happy to share some color on what we believe is an encouraging start to the early launch.

Chris: At the beginning of the year Barry highlighted our objective in establishing <unk> as the first line therapy for women with PPD.

Chris: We believe to do so will require delivering broad equitable and affordable access for women with PPD.

Chris: Enabling early positive HCP and patient experiences.

Chris: Partnering with communities to improve the focus on maternal mental health.

Chris: And providing clear education zubaie in PPD to all stakeholders.

Chris: With that in mind, we are encouraged by the demand we saw in the initial days of the launch let.

Chris Bunecki: Let me share some metrics we believe are important and reflective of the progress we've seen. As a reminder, we announced commercial availability in mid-December, so the data I'm sharing reflects demand from around 10 days when women with PPD could access HCP. As of the end of the fourth quarter, there were approximately 120 prescriptions written.

Chris: Let me share some metrics, we believe are important and reflective of the progress we've seen.

Chris: As a reminder, we announced commercial availability in mid December so the data I'm sharing reflects demand from around 10 days when women with PPD could access hep's.

Chris: As of the end of the fourth quarter, there were approximately 120 prescriptions written.

Chris Bunecki: With added launch capabilities and both SAGE and Biogen sales representatives active in the field, we continue to be encouraged by the increasing number of prescriptions in early 2024. I'd like to note that this is a metric we intend to show in the initial quarter. However, over time, we will likely move away from this metric and focus primarily on shipment and collaboration revenue.

Chris: With added launch capabilities in both Sage and Biogen sales representatives active in the field, we continue to be encouraged by the increasing number of prescription in early 2024.

Chris: I'd like to note that this is a metric we intend to show in the initial quarters. However over time, we will likely move away from this metric and focused primarily on shipments and collaboration revenue.

Chris Bunecki: In December, we were pleased to see prescriptions written by psychiatrists and, importantly, OBGYNs who prescribed in approximately equal numbers. We also saw a small number of prescriptions written by primary care physicians, and a number of HCPs wrote multiple. All of these trends have continued into early 2024. For example, of the prescriptions written in December, over 70% were shipped in December and early January. Our goal over time is for most women who are prescribed Zerzuvia to receive the medication as quickly as possible. However, we saw many scripts in December take longer to ship than we'd like, which can be anticipated in the initial days of launch and over a holiday period.

Chris: In December we were pleased to see prescriptions written by psychiatrists and importantly, obgyns, who prescribed an approximately equal numbers.

Chris: We also saw a small number of prescriptions written from primary care physicians.

Chris: And a number of Hep's wrote multiple prescriptions.

Chris: All of these trends have continued into early 2024.

Chris: Of the prescriptions written in December over 70% were shipped in December and early January.

Chris: Our goal over time is for most women who are prescribed <unk> to receive the medications as quickly as possible.

Chris: We saw many scripts in December take longer to ship than we'd like which can be anticipated in the initial days of launch and over a holiday period.

Chris Bunecki: We expect that as the launch progresses, women with PPD will have access to Zerzuve more rapidly, particularly as factors such as payer formulary decisions are made, HCPs and patients become more experienced with using our SP network, and the specialty pharmacy process is further optimized. Moving on, as Barry noted, our patient support program, Zouve for You, is activated and working well. In December, commercially insured patients using the Zerzube savings card paid no copay expenses.

Chris: We expect that as launch progresses women with PPD will have access to <unk> more rapidly, particularly as factors such as payer formulary decisions are made.

Chris: Hcp's and patients become more experienced and using our SP network and our specialty pharmacy process is further optimized.

Chris: Moving on as Barry noted our patient support programs. There's debate for you is activated and working well.

Chris: In December the commercially insured patients using <unk> savings card paid no co pay expenses.

Chris Bunecki: We maintain our commitment to the goal of having Zerzubei be both broadly acceptable and affordable for women with PTSD. And importantly, on the coverage front, conversations are advancing across national, regional, and government payers, and in the early weeks of the launch, the vast majority of SHIP prescriptions are being covered by payers, even as coverage policies are being developed. We are so far not encountering significant payer headwinds, and, to the contrary, we are seeing positive payer engagement. As we said, we expect commercial coverage formulary decisions to continue to come on board in the first half of 2024, with Medicaid stretching into the second half for certain states, as that process typically takes more time.

Chris: We maintain our commitment to the goal of having zubaie people broadly accessible and affordable for women with PPD.

And importantly on the coverage front conversations are advancing across national regional and government payers and in the early weeks of the launch the vast majority of shipped prescriptions are being covered by payers, even as coverage policies are being developed.

Chris: We have so far not encountering significant payer headwinds into the country, we are seeing positive payer engagement.

Chris: As we said, we expect commercial coverage formulary decisions to continue to come on board in the first half of 2024 with Medicaid stretching into the second half for certain states as that process typically takes more time.

Chris Bunecki: The early demand for Zerzuvia is reflective of the strong enthusiasm we're hearing from HCPs and women with PPD for this medication. Further, as we look at who is driving the prescribing, we believe that the strong engagement across specialties and providers represents HCP appreciation for the need to treat PPD as an urgent medical condition, regardless of the, And notably, these prescriptions are coming from HCPs, many of whom have been reached either through personal promotion or who have engaged with our website's digital content, reinforcing the initial impact of our omni-channel efforts. We're still in the early weeks of launch, and we know we have more work to do to help women with PPD access treatment. With that said, we're encouraged by what we're seeing so far.

Chris: The early demand for <unk> is reflective of the strong enthusiasm we're hearing from Hcp's of women with PPD for this medication.

Chris: Further as we look at who is driving the prescribing we believe that the strong engagement across specialties and providers represents HCP appreciation for the need to treat PPD is an urgent medical conditions, regardless of the practice setting.

Chris: Notably these prescriptions are coming from Hcp's, many of whom have been reached either through personal promotion.

Chris: Or who are engaged with our website digital content reinforcing the initial impact of our omni channel efforts.

Chris: We are still in the early weeks of launch and we know we have more work to do to help women with PPD access treatment.

Chris: With that said, we're encouraged by what we're seeing so far.

Chris Bunecki: The launch has reaffirmed the unmet need and urgency for a new medication for women living with PPD, and we know we need to continue to execute to maintain this momentum. I look forward to sharing additional details on InBiogen's commercialization efforts in the coming quarter. With that, I will turn it over to Laura for a more detailed discussion of our recent pipeline progress and current clinical expectations.

Chris: Lunch is reaffirm the unmet need and urgency for a new medication for women living with PPD.

Chris: And we know we need to continue to execute to maintain this momentum.

Chris: I look forward to sharing additional details on our and biogen's commercialization efforts in the coming quarters with that I will turn it over to Laura for a more detailed discussion of our recent pipeline progress and current clinical expectations Laura.

Laura Chico: Thanks, Chris, and good morning, everyone. In 2023, we have made important progress on our pipeline program. And I am pleased to share our recent progress and plans for continued development over the coming years. I want to share my excitement to be part of such a significant moment for maternal health with the launch of Zubay and the treatment of women with PPD. Not only are we seeing growing interest from HCPs to learn more about Suzy. But we believe the launch of the Zubay is a catalyst for positive change in screening, diagnosis, and treatment. We are seeing increased awareness and attention to PPV in the media and by professional organizations.

Laura Chico: Thanks, Chris and good morning, everyone.

Laura: For 2023, we have made important progress in our pipeline program.

Laura: And I am pleased to share our recent progress and plans for continued development over the coming quarters.

Laura: I want to share my excitement to be part of the question a significant moment for maternal health with lots of <unk> in the treatment of women with PPD.

Laura: Not only are we seeing growing interest from HCP to learn more about such a thing, but we believe the launch of those today as a catalyst for positive change in the screening diagnosis and treatment.

Laura: We are seeing increased awareness and attention the PPD in the media and by professional organization.

Laura Chico: This has increased knowledge about the cause of PPD and potential treatments and reduced stigma, making it easier for women to seek treatment. Further, I'm excited to see SoSuse being recognized by physicians, and OB-GYNs in particular, as a distinct new treatment option for women with CPD. It has a novel MOA and is a rapidly-acting, short-course treatment with a flexible approach that gives HCPs the option to use VA alone or in combination with other therapies. In a short period of time, we believe we are starting to see PPD move from a disease where some HCPs would suspect the diagnosis and refer for evaluation and treatment to one that HCPs are confident to diagnose.

Laura: This has increased knowledge about the cause of PPD and potential treatments and reduce stigma, making it easier for women to take care.

Laura: Further I'm excited to see firstly that being recognized amongst clinicians and Ob gyn in particular as a distinct new treatment option for women with PPD.

Laura: It has a novel MLA and as a rapidly acting short course treatment with a flexible approach that gives HCP has the option to users with asthma alone or in combination with other therapies.

Laura: In a short period of time, we believe we are starting to see people take some liberties with some hcp's with respect the diagnosis and refer valuation achievement.

Laura: It seems that ACP is a confidence to diagnose and treat.

Laura Chico: Supporting mothers has always been a core focus for us, and we are excited that we finally have an oral option for HCPs who want to offer more to women with TB. In addition to the work that we do in PPD, we have many interesting programs in our pipeline. Salve Mendor, also referred to as SAGE 718, is a program that we are really excited about. We are advancing Bell's Remember, our wholly owned, first-in-class NMDA receptor positive allosteric modulator, or PAMM, as a potential oral therapy for cognitive disorders associated with neurodegenerative diseases, including Cognitive Impairment and Huntington's Disease or HD. Parkinson's disease, PD, and Alzheimer's disease, AD. Disorders of Cognitive Impairment represent some of the greatest areas of unmet need in the... And we know that globally, they continue to increase in prevalence and pose significant challenges to patients in their everyday lives. The mechanism of action of daltonimbor is differentiated and leverages our deep understanding of how neuroactive steroids interact with the NMDA receptor.

Laura: So putting mother has always been a core focus for us and we are excited we finally have an oral option for HCP, we want to offer more to women with PPD.

Laura: In addition to the work that we do in PPD, we have many interesting programs in our pipeline.

Laura: <unk> also referred to as <unk> is a program that we are really excited about.

Laura: We are advancing <unk>, our wholly owned first in class NMDA receptor positive allosteric modulator or Pam.

Laura: As a potential oral therapy for cognitive disorders associated with neuro degenerative diseases.

Laura: Including cognitive impairment and huntington's disease or HD Parkinson's.

Laura: Parkinson's disease, TB and Alzheimers disease Adrian.

Laura: This order is a cognitive impairment represent some of the greatest area of unmet need in medicine.

Laura: We know that globally. They continue to increase in prevalence and posed significant challenges to patients in their everyday lives.

Laura: The mechanism of action and South nimble is differentiated and leverages, our deep understanding of how narrow active steroids interact with the NMDA receptor.

Laura Chico: A growing body of evidence suggests that NMDA receptor hyperfunction may occur in a wide range of neurodegenerative disorders associated with cognitive impairment, including Huntington's, Parkinson's, and Saldanandor is a novel molecule derived from our understanding of the pharmacology of a neuroactive steroid, 24S-hydroxycholesteroid, and the Endogenous NMDA Receptor. Dalton M. Dorr is believed to bind to the NMDA receptor with the potential of modulating NMDA receptor activity to improve cognition. We are encouraged by the consistent effects on important domains of cognition, such as executive function and learning and memory, that we've seen in our earlier studies in HC, PD, and AT. And we are excited to be progressing a clinical development program for Dalton M. Doar with five ongoing clinical trials. Starting with HD, the lead indication for Dalton-MDOR, we are currently enrolling in three studies in people with cognitive impairment due to high...

Laura: A growing body of evidence suggests that NMDA receptor hypofunction may occur in a wide range of neuro degenerative disorders associated with cognitive impairment.

Laura: Huntington's Parkinson's and Alzheimer's.

Laura: <unk> is a novel molecule July from our understanding of the pharmacology of interactive steroid.

Laura: For S hydroxy cholesterol.

Laura: And endogenous NMDA receptor Pam.

Laura: <unk> is believed to bind to the NMDA receptor with a potential of modulating NMDA receptor activity.

<unk> cognitive function.

We are encouraged by the consistent effects unimportance remains of cognition, such as executive function in learning and memory that we've seen in our earlier studies and HD PD and <unk>.

Laura: And we are excited to be progressing our clinical development program for <unk> thousand door with five ongoing clinical trials.

Laura: Starting with HD.

Laura: Indications of thousand door, we are currently enrolling in three studies.

Laura: Kenneth impairment due to Huntington.

Laura Chico: The DIMENSION study is a double-blind, placebo-controlled, phase 2 study designed to evaluate the efficacy of one daily Dalton-MDOR dosed over three months. The Surveyors Club is a double-blind placebo-controlled safety study designed to generate evidence linking efficacy signals of cognitive performance to real-world function. And the PURVIEW study is an open-label, phase-three safety study of Deltin-M dorms designed to evaluate the long-term safety profile and long-term functioning compared to HD natural history studies. As a reminder, the primary objective of the Surveyor Study is to understand the magnitude of the cognitive impairment in high school students. Relative to healthy individuals

Laura: The dimension study is a double blind placebo controlled phase II study.

Laura: Assigned to evaluate the efficacy of once daily dosing them door dosed over three months.

Laura: That's what they're studying.

Laura: It's a double blind placebo controlled phase II study designed to generate evidence linking efficacy signals of cognitive performance to real world functioning.

Laura: And the perfect study is an open label Phase III safety study a thousand door design.

Laura: Designed to evaluate the long term safety profile and long term functioning compared to HC natural history study.

Laura: As a reminder, the primary objective Episurveyor study is to understand the magnitude of the cognitive impairment and Huntington relative to healthy individuals.

Laura Chico: A key secondary objective is to advance our understanding of the effects of Delsin-MDOR on cognition and function in participants with, It's important to note that the Surveyor Study is not designed or powered to show statistically significant differences between Delsin-MDOR and placebo. Overall, these data are meant to complement third-dimension studies by generating evidence to better define clinically meaningful change and the Relationship Between Changes in Cognition. Moving now to our PD and AB studies for Delta. The precedent study is a double-blind, placebo-controlled, phase 2 study in people with mild cognitive impairment due to Parkinson's disease designed to evaluate the safety and efficacy of their therapy. The LIGHTWAVE study is a similarly designed Phase 2 study to evaluate the safety and efficacy of Delsin-MDOR in people with mild cognitive impairment and mild dementia due to age.

Laura: A key secondary objective is to advance our understanding of the effects of thousands or unconditioned assumption in participants with Huntington.

Laura: It's important to note that.

Laura: The severe study is not designed or powered to show a statistically significant differences between <unk> and placebo.

Laura: Overall these data are meant to complement the dimension study by generating evidence to better define clinically meaningful change in the relationship between changes in cognition and function.

Laura: Moving now to our PD and <unk> studies for 1000 doors.

Laura: The precedent study.

Laura: Double blind placebo controlled phase III study in people with mild cognitive impairment due to Parkinson's disease.

Laura: Signed to evaluate the safety and efficacy of <unk> thousand ignored.

Laura: The lightweight study is it similarly designed phase II study.

<unk> safety and efficacy of thousand door and people with mild cognitive impairment and mild dementia due to aging.

Laura Chico: We expect to announce top-line data from Precedence for PD in early 2020. Surveyor for HD in mid-2024, and Dimension for HD and LightWave for AD, both in late. We're very excited for these readouts, and if positive, they will help demonstrate a path forward for Delta and MDoOR, and importantly, bring us one step closer to helping Turning to SAGE 3G-4, which is an investigational positive allosteric modulator of GABA-A receptors with significant potential in the treatment And it has a significant impact on an individual's ability to perform every day, including medical, loss of employment, and disability.

Laura: We expect to announce topline data from precedent for PD in early 2024.

Laura: Here for HD in mid 2024, and dimension for HD and lightweight for adding both in late 2024.

We're very excited for these readouts and if positive they will help demonstrate a possible which per thousand door and importantly, bring us one step closer to helping patients.

Laura: Turning to page three Q4, which is an investigational positive allosteric modulator of Gaba a receptors with significant potential and achievements movement disorders like essential tremor.

Laura: Essential tremor has suffered from a lack of innovation with no new approved treatments and more than 50 years.

Laura: And it has a significant impact on an individual's ability to perform everyday task.

Laura: In the U S. The total annual estimated economic impact of essential tremor is over 100 billion.

Laura Chico: We are excited about the potential of SAGE 324 in Essential Terminals, a program that we are developing in collaboration with BIOS. As a reminder, the kinetic study demonstrated statistically significant reductions at baseline in upper limb tremor. Kinetic 2 is a 3-month study designed to identify a dose with a safety and tolerability profile that is suitable for use of SAGE 324 as a chronic treatment in essential tremor. While the primary endpoint for Kinetic-2 is a change from baseline in upper limb tremor amplitude, we will also evaluate a modified version of the Tetris ADL to give us directional insight into the effects of SAGE 324 We have completed enrollment at Connecticut and expect to report top-line data mid this year. Lastly, I'd like to share our excitement around the earlier SAGE Pipeline. In particular, I'd like to highlight two novel molecules.

Laura: Including medical loss of employment and disability call.

Laura: We are excited about the potential of phase three to four in essential tremor program that we are developing in collaboration with Biogen.

Laura: As a reminder, the kinetics study demonstrated statistically significant reductions from baseline and upper limb tremor amplitude.

Laura: And then two is the three months study designed to identify a dose with the safety Tolerability profile that is suitable for use of phage therapy for a chronic treatment in essential tremor.

Laura: While the primary endpoint for kinetic two is a change from baseline and upper limb tremor amplitude.

Laura: We will also evaluate a modified version of the TETRAS ADL, they give us directional insight into the effects of stage three to four on quality of life and activities of daily living.

Laura: We have completed enrollment of kinetic two and expect to report top line data mid this year.

Laura: Lastly, I'd like to share our excitement around the earlier stage pipeline in particular I'd like to highlight two novel molecule Sage.

Laura Chico: SAGE 319, our extrasynaptic GABA-A receptor, and SAGE 14-1, our NMDA. We look forward to sharing more about these programs as they progress. In closing, I am proud of our pipeline efforts this year, and I look forward to our future progress and clinical execution throughout a catalyst-rich 2020. Now, I'll turn the call over to Kimi for a review of our financials. Kimi

Laura: Page 31 line or extra synaptic Gaba a receptor Pam.

Laura: And page 41, our NMDA receptor Pam.

Laura: We look forward to sharing more about these programs as they progress.

Laura: In closing I am proud of our pipeline efforts this year and I look forward to our future progress and critical execution throughout a catalyst rich 2024.

Speaker Change: Now I'll turn the call over for a review of our financials to me.

Kimi E. Iguchi: Thanks, Laura. Our financial results for the fourth quarter and full year 2020 are detailed in our press release issued this morning. Before discussing specifics, I want to share my excitement for the recent launch of DERJUVE and the opportunity to help so many women suffering with TPD. I also want to thank the entire SAGE team for their continued support and dedication to our mission to support brain health patients. We in Biogen are mobilized with the goal of continued commercial momentum and are jointly supporting the planned launch of Zerzubei with 50-50 cost sharing in the United States.

Speaker Change: Thanks, Laura.

Laura: Our financial results for the fourth quarter and full year 2020 are detailed in our press release issued this morning.

Speaker Change: Before discussing the specifics I want to share my excitement on the recent launch of <unk> and the opportunity to help so many women suffering with PPD.

Speaker Change: I also want to thank the entire stage team for their continued execution and dedication to our mission to support brain health patients.

Speaker Change: We and Biogen are mobilized with the goal of continued commercial momentum and are jointly supporting the planned launch of <unk> with 50 50 cost sharing in the United States.

Kimi E. Iguchi: While we're thinking big about the opportunity, we're executing with a focused approach and plan to scale with success. In addition, we are prepared to execute on a catalyst-rich year ahead with multiple expected top-line data readouts for Dalvin M. Doerr and SAGE 324. We're investing strategically in our broader pipeline to have the potential for value creation opportunities for the near, mid, and long term. Now, I'll turn to the panel. Today, we announce collaboration revenue from the initial sales of the Jouvet of $824,000. As a reminder, our reported collaboration revenue is 50% of the net revenue by Zoom reports for ZOOZOOVAN. Net revenues are recorded when buy-inships are due to the distributors and are not based on the number of prescriptions delivered from specialty pharmacies to patients.

Speaker Change: While were thinking big about the opportunity, we're executing with a focused approach and plan to scale with success.

Speaker Change: In addition, we are prepared to execute on a catalyst rich year ahead with multiple expected top line data readouts for <unk> and stage through 'twenty four.

We're investing strategically in our broader pipeline to have the potential for value creation opportunity for the near mid and long term.

Speaker Change: I'll now turn to the financials.

Speaker Change: Today, we announced collaboration revenue from initial sales of <unk>.

824000.

Speaker Change: As a reminder, our reported collaboration revenue 50% of the net revenues Biogen. Unfortunately, you do that.

Speaker Change: Net revenues are recorded when Biogen shippers are they to the distributors and are not based on the number of prescriptions delivered from specialty pharmacy to patients.

Kimi E. Iguchi: The RejuvenNet revenues in December 2023 principally represent initial efforts of preparing the channel for the full launch in the first quarter of 2023. Additionally, today we announced milestone revenue of $75 million from Biogen related to the first commercial sale of Zuzube for the treatment of TPD. We earned the milestone in Q4 and received payment in January 2020. We're not guiding on gross to net today, other than to say, given the fact that Desuve is a novel medication and the only approved oral treatment for women with PPD, we do not anticipate the type of discounting we see for other branded CNFs. Turning to operating expenses, R&D expenses were $64.3 million in the fourth quarter of 2020, and SG&A expenses were $55.1 million in the fourth quarter of 2020.

Speaker Change: Theres, giving net revenues in December 2023, principally represent initial efforts of preparing the channel for the full launch in the first quarter of 2024.

Speaker Change: Additionally, today, we announced milestone revenue of $75 million from Biogen related to the first commercial sale of <unk> for the treatment of PPD.

Speaker Change: We earned the milestone in Q4 and received payment in January 2024.

Speaker Change: We're not guiding on gross to net today other than to say given the fact that the USA as a novel medication and.

Speaker Change: The only approved oral treatment for women with PPD, we do not anticipate that type of discounting receive for other branded TNF agents.

Speaker Change: Turning to operating expenses.

Speaker Change: R&D expenses were $64 3 million in the fourth quarter of 2023.

Speaker Change: SG&A expenses were $55 1 million in the fourth quarter of 2023.

Kimi E. Iguchi: The decrease in both R&D and SG&A expenses compared to the fourth quarter of last year was primarily related to reorganization cost-saving measures such as reduced headcounts, budgeted expenditures, and prioritization of early pipeline programs. We expect that operating expenses will decrease in 2024 relative to 2020. The cost of revenues for the fourth quarter of 2023 included one-time charges in preparation for commercial availability. These one-time charges include a distribution set-up fee and charges for manufacturing. We do not expect this gross margin trend to continue. Our net loss for the fourth quarter of 2023 was $32.7 million, and we ended the fourth quarter of 2023 with cash, cash equivalents, and marketable securities of approximately $753 million.

Speaker Change: The decrease in both R&D and SG&A expenses compared to the fourth quarter of last year was primarily related to reorganization cost saving measures such as reduced head count budgeted expenditures and prioritization of early pipeline programs.

Speaker Change: We expect that operating expenses will decrease in 2024 relative to 2023.

Speaker Change: Cost of revenues for <unk> for the fourth quarter of 2023 included onetime charges in preparation for commercial availability.

Speaker Change: These one time charges included distribution setup fees and charges for the manufacturing network.

Do not expect this gross margin trend to continue.

Our net loss for the fourth quarter of 2023 was $32 7 million and we ended the fourth quarter of 2023 with cash cash equivalents and marketable securities of approximately $753 million.

Kimi E. Iguchi: We are reaffirming that based on our current operating plan, we anticipate cash, cash equivalents, and marketable securities, along with a milestone payment received in January, anticipated funding from ongoing collaboration, and estimated revenues will support operations into 2020. I'd like to note that we have maintained a strong financial foundation as we enter a catalyst-rich year for the economy. Before I turn the call over to you, I want to highlight the scope of our potential as a growing leader in brain health. The launch of Zerzouve demonstrates the culmination of our capabilities, starting from molecule discovery to SAA approval and now commercial law. We look forward to the year ahead with many exciting catalysts across our pipeline and the continued commercialization of jujube in the treatment of women with PPD. I'll now turn it over to Ashley to handle the Q&A with Yatin. Ashley

Speaker Change: We are reaffirming that based on our current operating plan, we anticipate cash cash equivalence and marketable securities along with a milestone payment received in January anticipated.

The anticipated funding from ongoing collaboration and estimated revenues will support operations into 2026.

Speaker Change: I'd like to note that we have maintained a strong financial foundation as we enter a catalyst rich year for the company.

Speaker Change: Before I turn the call over I want to highlight the scope of our potential as a growing leader in greenhouse.

Speaker Change: <unk> demonstrates the culmination of our capabilities.

Speaker Change: Starting from molecule discovery to FAA approval and now commercial launch.

Speaker Change: We look forward to the year ahead with many exciting catalysts across our pipeline and the continued commercialization of <unk> in the treatment of women with PPD.

Speaker Change: I'll now turn it over to Ashley to handle Q&A with the offering.

Speaker Change: Ashley.

Ashley Kaplowitz: Thanks, Kimi. I'll ask that you limit yourself to one question. If you have an additional question, feel free to return to the Q&A. Now, I'll turn it over to the operator to handle the Q&A. Operator.

Ashley Kaplowitz: Thanks, Kimi I'll ask that you limit yourself to one question if.

Ashley Kaplowitz: If you have an additional question feel free to return to the queue.

Ashley Kaplowitz: Now I'll turn it over to the operator to handle Q&A operator.

Operator: Thank you. If you would like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure that your mute function is turned off to allow your signal to reach our equipment.

Thank you if you would like to ask a question. Please signal by pressing star one on your telephone keypad.

Ashley Kaplowitz: If you are using a speaker phone. Please make sure that your mute function is turned off to allow your signal to reach our equipment.

Operator: Again, you may press star 1 to ask a question. We'll pause for just a moment to allow everyone an opportunity to, Our first question comes from Salveen Richter with Goldman Sachs. Please go ahead. Great, thanks, this is Matt on behalf of Salveen.

Operator: Again, you May press star one to ask a question.

Operator: We'll pause for just a moment to allow everyone an opportunity to signal.

Operator: Our first question comes from Sal <unk> Richter with Goldman Sachs. Please go ahead.

Salveen Richter: Great. Thanks. This is Matt on for <unk> for.

Chris Bunecki: For the 120 scripts, could you share roughly what the split was between commercial and Medicaid and also between treatment-naive and treatment-experienced patients? Thank you. Hey Matt.

Salveen Richter: 120 scripts could you share roughly what the split was between commercial and Medicaid and also between treatment nave and treatment experienced patients. Thank you.

Chris Bunecki: Thanks for the question. Appreciate it. You know, as we talked about on the call, you know, the December numbers represent about 10 days where moms experiencing symptoms of PPD could access health care providers. We can't really provide much more color on the 120 scripts. We're happy with that kind of activity, and we're really excited that the prescriptions came not only from psychiatrists, but from OBGYNs as well as primary care. We don't have all the patient journey data in yet, but we'll certainly provide more color in the quarters to come. We'll take our next question from Anupam Rama with J.P. Morgan. Please go ahead. Hey, guys.

Salveen Richter: Hey, Matt Thanks for the question appreciate it.

Salveen Richter: As we talked about on the call.

Speaker Change: The December numbers represented about 10 days where bombs experiencing.

Matt: <unk> symptoms in PPD could access health care providers, we can't really provide much more color on the on the 120 scripts, we're happy with that kind of activity and we're really excited that the prescriptions came not only from psychiatrists, but from <unk> as well as primary care. We don't have all the patient journey data and yet we will certainly provide.

Matt: More color in the quarters to come.

Matt: We will take our next question from Edison <unk> Rama with JP Morgan. Please go ahead.

Barry E. Greene: Thanks so much for taking the question. Yesterday on the Biogen Earnings call, they mentioned, you know, positive payer dynamics. You guys talked about this this morning as well. Maybe you could expand on what you're seeing in the experience to date on the payer side and how we should think about that, you know, sort of first half sort of payer dynamic. Thanks so much.

Edison Rama: Hey, guys. Thanks, so much for taking the question.

Matt: Yesterday on the Biogen earnings call they mentioned.

Edison Rama: Positive payer dynamics you guys talked about this this morning as well maybe you could expand on what Youre seeing on the experience to date on the payer side.

Matt: And how we should think about that sort of first half.

Edison Rama: First half sort of payer dynamics. Thanks, so much.

Barry E. Greene: Yeah, I'll start, Ana Palma, and turn it over to Chris, and thank you very much for the question. It's really important. So, as you heard yesterday from our colleagues at Biogen, and we've commented on earlier, we're experiencing very positive payer dynamics. The vast majority of prescriptions, this is even before formulary coverage, were paid for, which we highly expected.

Speaker Change: Yeah, I'll start and upon and then turn it over to Chris and Thank you very much for the question. This is really important so as you heard yesterday from our.

Speaker Change: Our colleagues at Biogen and we've commented on earlier.

Chris: We're experiencing very positive payer dynamics the vast majority of prescriptions. This is even before formulary coverage, we're paid for which we highly expected where we'd been in PPD for a long time and the fact that mental health in maternal health are top of mind for payers really provides a positive tailwind.

Barry E. Greene: We've been in PPD for a long time, and the fact that mental health and maternal health are top of mind for payers really provides positive tailwinds in the long term. So, we're excited by what we're seeing in terms of reimbursement, even before coverage decisions have been made. But, Chris, do you want to provide more color?

Chris: So we're excited about what we're seeing in terms of a reimbursement even before coverage decisions have been made but Chris you want to provide more color yeah. What we've historically said that to be truly transformational you have to be accessible and we've worked hard over the course of the last several years to really establish the unmet need in PPD and to really share the data associated with.

Chris Bunecki: Yeah, we've historically said that to be truly transformational, you have to be accessible, and we've worked hard over the course of the last several years to really establish the unmet need for PPD and to really share the data associated with Zerzuve, particularly for the treatment of women with PPD. And we've been able to build on that as we've progressed into more formal formulary coverage discussions with payers. It's very noted in his opening remarks that initially, before formulary decisions were made, commercial and government insurers, particularly Medicaid, were actually paying for prescriptions as they flowed through.

Chris: <unk>, particularly for the treatment of women with PPD and we've been able to build on that as we progressed into more formal formulary coverage discussions with Payors as Barry noted in his opening remarks, we've seen initially before formulary decisions were made commercial and government insurers, particularly Medicaid actually paying for prescriptions as they flow.

Chris Bunecki: And we believe this is really reinforcing what we've already communicated, that there is the potential for Zerzuve to be a first-line therapy for women with PPD without the onerous prior authorizations and complex step edits that could challenge that. So we're really excited about the initial conversations that we've had with payers. Our next question comes from Yasmin Rahimi with Piper Sandler. Please go ahead. Hi, this is Jungu on behalf of Yaza Piper.

Chris: Through so we believe this is really reinforcing of what we've already communicated that there is the potential for us today to be a first line therapy for women with PPD without the onerous prior authorizations and complex step edits that could challenge that so we're really excited around the initial conversations that we've had with payers so far.

Yeah.

Chris: Our next question comes from Yasmin Rahimi with Piper Sandler. Please go ahead.

Speaker Change: Hi, This is John Gould on for younger paper. Thanks for taking our question for 701 <unk> what are the key gating factors in bars across studies to warrant further investment and for essential tremor, given the competitive landscape. What do you need to show to move into phase III in terms of safety and efficacy. Thank you.

Barry E. Greene: Thanks for taking our question. For 718, what are the key gating factors and bars across studies to warn of further investment? And for Essential Tremor, given the competitive landscape, what do you need to show to move into phase three in terms of safety and efficacy? Thank you.

Speaker Change: Yes so.

Speaker Change: When you are talking about Sage <unk> Sage 324.

Barry E. Greene: So, SAGE 3-2-4 is our partnered program with Biogen, a GABA-PAM designed for chronic administration for movement disorders initially studied in essential tremor. I'll start, and then Laura can talk about the Kinetic-2 study. So, early on, we saw a statistically significant reduction in tremor amplitude correlated with activities of daily living in Kinetic. What we're looking for in Kinetic-2 is the optimal dose for

Speaker Change: Is are our partnered program with Biogen, a Gaba Pam design for chronic administration for movement disorders. Initially studied in essential tremor I'll start and Laura can talk about the Kinect two study as we saw early we saw statistically significant reduction in tremor amplitude.

Correlated with activities of daily living and kinetic what we're looking for in Q2 is the optimal dose for chronic administration Lori will talk more about the competitive landscape and what we're looking for sure.

Laura Chico: Laura, you want to talk more about the competitive landscape and what we're looking for? Sure. So, we learned a lot from Kinetic-1 in terms of how we defined Kinetic-2.

Lori: We've learned a lot from Connecticut, one in terms of how we defined kinetic two and kinetic won the dose administered with 60 milligrams and it was administered in the evening.

Laura Chico: In Kinetic 1, the dose administered was 60 milligrams, and it was administered in the evening, and many patients had sedative effects or fondness. Before designing the KINETIC-2 study, we took that into consideration and did a number of things. First, we changed the administration of the drug to the evening so that the effects of formalin and sedation would be less problematic.

Lori: And many patients had sedative effects or somnolence.

Lori: We're defining the kinetic two study we took that into consideration that did a number of things first we changed the administration of the drug to the evening, so that the effects of sunlight sensation with less problematic and we also are exploring a variety of doses 50.

Laura Chico: And we also are exploring a variety of doses, 50 milligrams, 30 milligrams, and a titration. With that in mind, we feel confident that these data will allow us to identify a dose that has an appropriate risk-benefit profile for chronic use. With that said, what we're looking for is where that goes, for 3P4 to be a dose that provides efficacy that's similar to or better than agents that are used currently to treat with a safety and tolerability profile that's appropriate for chronic dosing. And will I talk about the competitive landscape?

Lori: 50 milligrams 30 milligrams titration is 60 milligrams with that in mind, we feel confident that these data will allow us to identify a dose that has an appropriate risk benefit profile for chronic use.

But as I've said before we're looking for as it were that dose for three to four.

Lori: Is that.

Lori: That is by its efficacy that similar to or better than agents that are used currently to treat <unk>.

Lori: With the safety Tolerability profile, that's appropriate for chronic dosing in this population.

Laura Chico: There's really been a paucity of innovation in central tremor, so we want to talk about what's out there. Yeah, it's really incredible.

Lori: And what I'm talking about the competitive landscape Theres really been a paucity of innovation is central to them or if you want to talk about what's out there yeah. It's really incredible there have not been new products approved in the central tremor for more than 50 years.

Laura Chico: There have not been new products approved for central tremor for more than five years. The last one approved was for panel. And there have been a number of companies who have ventured into this space recently, all with T-type calcium channel blocks. However, the data from some of these programs has been negative, and the programs have been stopped.

Lori: Just wanted to prove to us for Panama.

Lori: And there have been a number of combination of a bunch of it into the space recently I'll, let T type calcium channel blockers.

Lori: The data from some of these programs has been negative in the programs have been stopped in other cases. The programs are moving forward with Jocelyn practices and we look forward to seeing their results.

Laura Chico: In other cases, the programs are moving forward with jazz and..., and we look forward. We'll move to our next question from Ritu Baral with T.D. Cowan.

Lori: Yeah.

Lori: Well move to our next question from Ritu <unk> with TD Cowen. Please go ahead.

Barry E. Greene: Please go ahead. Hi guys, I wanted to ask about plans for the formal QTB launch, as you guys see it. You know, on the one hand, there was a huge sort of flurry of news reports, et cetera, around first approval. I understand that there was a commercial or a media outreach campaign around that.

Ritu: Hi, guys.

Ritu: Wanted to ask about.

Ritu: Plans for the formal CPD launch as you guys see it.

Ritu: On one hand, there was a huge sort of flurry of news reports et cetera around first approval I understand that there was.

Ritu: A commercial or a media outreach campaign around that.

Barry E. Greene: I think there's just a concern among investors interested in this program that you might be losing momentum, essentially, as we get further and further out from actual approval and availability and, you know, not pushing the button on something like another media push, especially given what you've said about patients themselves advocating for access to SIRSUVE when we found in our own checks that many OB-GYN clinicians are still unaware of the drug, still, amazingly Can you talk about the rationale for and the status of... Thank you. Yeah, Ritu, thanks for the question. So just to be clear, XerXuBe has been launched.

Ritu: Yeah.

Speaker Change: I think theres just a concern amongst investors interested in this program that you might be losing momentum essentially as we get further and further out from actual approval and availability.

Speaker Change: And.

Speaker Change: Not pushing the button on something like another media push, especially given what you've thought about patients themselves are advocating for access just received as and when we found in our own checks, but many other Julien clinicians are unaware of the trucks still amazingly enough.

Speaker Change: Can you talk about the rationale for the status of <unk>.

Speaker Change: Timing of that real commercial launch what aspects you can talk about now that will go into it.

Speaker Change: Why you're waiting frankly armed them.

Speaker Change: If I could sneak another one in another question just about the free drug program that you have right now for sure. Thank you.

Speaker Change: Yeah Ritu. Thanks for the question. So just to be clear Zubaie is launched we received approval in as you know in August for PPD, DEA scheduling, which took several months and we invited you made.

Barry E. Greene: We received approval, as you know, in August for PPD. We had DEA scheduling, which took several months, and we invited and made XerXuBe commercially available in mid-December. We now, in January, have our full, you know, omnichannel up and running, and our field force deployed. As you heard us say previously, as Kimi said on the call, we're thinking big about the PPD opportunity. But start with focusing and scaling fast.

Ritu: As usual with a commercially available mid December we now in January have a full omni channel up and running in our field force deployed.

Ritu: <unk> heard us say previously as Kimi said on the call, we're thinking big about the <unk> opportunity, but starting with focus in <unk> and scaling fast.

Chris Bunecki: The media attention has continued, and the sort of anecdotes and stories have continued well, and we're not seeing any slowing at all of momentum. So we're excited by and encouraged by what we're seeing. The patient advocacy groups are certainly encouraged, and as you heard us say, we're beginning to see women with PPD stepping up and advocating. The other important, major trends that we're seeing, and I'll highlight this, are that PPD is seen as a serious medical condition and not a moral failing. That switch happened relatively fast. The other switch that happened relatively fast, I'm sort of surprised if you've polled OBGYNs and they're not aware of XerXuBe. We certainly haven't encountered that. You'd have to sort of be under a rock to not have seen the media attention, which has continued.

Ritu: The immediate attention has continued to need sort of anecdotes and stories have continued well and we're not seeing any slowing at all of momentum. So we're excited by and encouraged by what we're seeing the patient advocacy groups are certainly encouraged and as you've heard us say.

Ritu: We are beginning to see women with PPD stepping up and advocating the other important major trends that we're seeing I'll highlight this our PPD is seen as a serious medical condition and none of moral failing that that switch happened really relatively fast the other switched it happened relatively fast I'm sort of sort of.

Ritu: You've pulled obgyns, who are not aware of zippy, we certainly haven't encountered that you'd have to sort of be under a rock to not have seen the media attention, which has continued but.

Chris Bunecki: But the big trend here is that we're seeing some healthcare providers move from suspicion of depression and referral to diagnosis and treatment. And the fact that the prescriptions have come equally from psychiatric care and OBGYN is a good proof point of that trend that we're seeing. You also asked, Chris, do you want to talk about the free drug program? Yeah, so let's take a step back and talk about Zerzuvia for You, the patient access program that we have in place that's been up and running since the launch of the medication in mid-December, as we've noted. Zerzuvia for You has been particularly effective in terms of mitigating patient out-of-pocket costs, those with commercial insurance, down to zero. Everybody that's enrolled in the program has paid zero dollars in order to get Zerzuvia.

Ritu: The big trend here is that we're seeing some health care providers move from the suspicion of depression, and the referral to the diagnosis and treatment and the fact that the prescriptions come equally from sites and Obgyn is a great proof point of that trend that we're seeing.

Ritu: You also asked Chris you were talking about the free drug program. So so let's take a step back and talk about <unk> for you. The patient access program that we have in place that's been up and running since the launch of the medication in mid December as we've noted so as you've made for you has been particularly effective in terms of mitigating patient out of pocket those with commercial insurance down to zero everybody that's enrolled in the <unk>.

Ritu: Graham who is paid zero dollars in order to get <unk>. So it's been particularly effective in making sure that not only is the medication accessible but it's also affordable thats, particularly key I think in terms of the free good program. We've got mechanics in place if a payer is not particularly going to pay for the medication. After a set period of time.

Chris Bunecki: So it's been particularly effective in making sure that not only is the medication accessible, but it's also affordable. That's particularly key. I think in terms of the free good program, you know, we've got the mechanics in place. If a payer is not particularly going to pay for the medication after a set period of time, we'll actually step in and provide the medication to that patient at no out-of-pocket cost to that patient. We've seen the vast majority of prescriptions actually be covered prescriptions going forward. We haven't actually had to actually enact that program significantly, reflective of, as I said earlier, the support that we've seen from the payer community around making sure that this medication is available and flows through, regardless of the fact that patients are either commercial or Medicaid. So, you know, we see Zerzuvia for You as a particularly effective program and one that we'll continue to implement in order to make sure all patients have access. Now, we'll move to our next question from Paul Matteis with Stiefel. Please go ahead. Hi, this is James on behalf of Paul.

Ritu: Actually step in and provide the medication to that patient at no out of pocket.

Ritu: We've seen the vast majority of prescriptions actually be covered prescriptions going forward, we havent had to actually enact that program significantly reflective of as I said earlier to support that we've seen from the payer community around making sure that this medication is available and flows through regardless of the fact that.

Ritu: Payers are regardless of the fact that patients are either commercial or where Medicaid. So we see you as a particularly effective program and one that will continue to implement in order to make sure all patients have access to the medication.

Ritu: Well move to our next question from Paul <unk> with Stifel. Please go ahead.

Ritu: Hi, This is James on for Paul Thanks for taking our question.

James: Thanks for taking our question. Kind of a similar question there around, you know, of those 50 scripts that have actually shipped and been delivered, what percent are actually paid for? And it sounds like just based on your prior answer, it's the majority.

Speaker Change: Kind of a similar question there around you know.

James: Of those 50 scripts that I've actually shifting but been delivered what percent are actually paid drug and it sounds like just based on your prior answer it's the majority and I guess kind of baked into that just wondering what youre kind of seeing on that.

James: And I guess kind of baked into that, just wondering what you're kind of seeing on a time lag basis from when a script is written to when it's actually, you know, given to the patient. You know how you expect to see that evolve over time. Thanks so much.

James: Timeline basis from when a script is written and when it's actually given to the patient.

Speaker Change: How you expect to see that evolve over time, thanks, so much.

Barry E. Greene: Yeah, James, thanks for the question. Let me just take a step back and just clarify kind of the flow. So when we ship a drug to a specialty pharma, that shipment to the specialty pharma is the revenue recognition. When a prescription is written, it's typically in the electronic medical system, it's automatically sent to a specialty pharma.

Speaker Change: Yeah, James Thanks for the question, let me just take a step back and just clarify kind of the flow. So when when we shipped drug to a specialty pharma that shipment to the specialty pharma is the revenue recognition when a prescription is written it's typically in the electronic medical system, it's automatically sent to a specialty pharma that counts as a prescription.

Barry E. Greene: That counts as a prescription. When that specialty pharma then ships the prescription to the patient's home, that's a shipment. So those are kind of the three key metrics. The vast majority of those shipments were paid for, as we said. We're not providing a specific breakdown, but the vast majority, as Chris already mentioned, have been paid for not only by commercial payers but also by government payers, specifically Medicaid.

Speaker Change: <unk> when that specialty pharma, then shifts the prescription to the patient's home that's the shipment. So those are the kind of the three.

Speaker Change: Key metrics.

Speaker Change: The vast majority of those shipments were paid for as we said, we don't have without providing specific breakdown, but the vast majority of that as Chris already mentioned, it's been paid for not only by commercial but also by government payer specifically Medicaid. So we're excited by.

Barry E. Greene: So we're excited by that. We continue to work on the value proposition here. Obviously, Zuzube is the first and only oral medication specifically approved for PPD. Its rapid onset of activity is key to the value proposition. So the sooner mom gets the drug, the better off mom is to reattach with family and baby. So we're cognizant of that. We had many shipments that were done in 24 to 40 hours.

Speaker Change: That.

Speaker Change: We continue to work on the value proposition here, obviously is vis vis the first and only oral medication specifically approved for PPD. Its rapid onset of activity is key to the value proposition. So the sooner mom gets drug the better off mom is three attach with family and baby sort, we're cognizant of that.

Speaker Change: We had many shipments that were done in 24 to 40 hours of course, some took took longer so that's really the engineering issue as we optimize the processes payers come online and health care providers get comfortable with exactly how to get through debate of moms again highly encouraged in the early days.

Barry E. Greene: Of course, some took longer, so that's really an engineering issue as we optimize the processes, payers come online, and health care providers get comfortable with exactly how to get Zuzube to moms. But again, highly encouraged in the early days.

Speaker Change: Yeah.

Tazeen Ahmad: We'll move to our next question from Tazeen Ahmad with Bank of America. Please go ahead. Hi, thanks for taking my question. With regard to the prescriber base that you've talked about for a bit, and just coming in from the OBs, in addition to psychiatrists, but how important is it going to be to penetrate PCPs, and what is your strategy? Can you just remind us of how the sales force is structured? Does a salesperson just target a particular specialty, or are they discussing all three specialties at the same time?

Speaker Change: Well move to our next question from <unk> with Bank of America. Please go ahead.

Speaker Change: Hi, Thanks for taking my question with regards to the prescriber base and you've talked about now.

Speaker Change: For debt interest coming in from from the lbs.

Speaker Change: In addition to psychiatrists, but how important is it going to be and to penetrate PC piece and what is your strategy can you just remind us of how the sales force is structured.

Speaker Change: There's a sales person just target a particular specialty or are they detailing all three specialties at the same time. Thanks.

Barry E. Greene: Thank you. Yeah, Tazeen, thanks for the question. I'll start, and then Chris can provide more colors.

Speaker Change: Yes. Thanks for the question I'll start and then Chris will provide more color so you'll again.

Chris Bunecki: So, you know, again, the fact that, for literally, about 10 days that Zuzube was available, we already saw prescriptions coming in, not only from psychiatric hospitals but also OBGYNs and primary care is really indicative of the recognition of PPD as a severe medical condition, not a moral failing, and the awareness that our omni-channel approach and the media had in raising awareness of PPD. Chris, do you want to talk about Salesforce targeting omni-channel and sort of how we were approaching that? Yeah, Barry, what I would say first is that what I think we're seeing here is obvious.

Speaker Change: The fact that literally the about 10 days.

Speaker Change: Zubair was available.

Speaker Change: That short period of time, we already saw prescriptions coming in not only from <unk>, but also <unk> primary care is really indicative of the recognition of PPD as a severe medical condition not a moral failing and the awareness that that our omnichannel approach and the <unk>.

Speaker Change: Media had in raising awareness of PPD.

Speaker Change: Chris you want to talk about the sales force targeting omnichannel and sort of how we're approaching it yes, Barry what I would say first is that what I think we're seeing here is a paradigm shift.

Chris Bunecki: Historically, what's happened in the diagnosis and treatment of PPD is clinicians have suspected, and then they've referred out. What we're actually seeing here are clinicians, the clinicians that we're calling on, the clinicians that we're reaching through Omnichannel, diagnosing and treating, which is very different than what we've historically seen. In terms of the call universe that we're calling on, we are calling on high-prescribing, high-volume clinicians with experience in treating postpartum depression. It's a mix of OBGYNs, psychiatrists, and a handful of PCPs that are all a part of that cohort that we're calling on actively with a sales force. Obviously, we're using Omnichannel to broaden our reach and deepen our frequency because we believe all clinicians who see women with PPD need to hear the messages that we're delivering and have access to the information to enable them to effectively treat women with PPD as we go forward.

Chris: Historically, what's happened in the diagnosis and treatment PPD as clinicians have suspected and then they've referred out what we're actually seeing here our clinicians to clinicians that were calling on the conditions that we're reaching through omnichannel diagnosing and treating which is very different than what we've historically seen.

Chris: In terms of the call universe that we're calling on we are calling on high prescribing high volume clinicians with experience in treating postpartum depression, it's a mix of Obgyns psychiatrist and a handful of <unk> that are all a part of that cohort that we're calling on actively with our salesforce, obviously, we're using omnichannel to broaden our reach in.

Chris: Deepen our frequency because we believe all clinicians who see women with PPD need to hear the messages that we're delivering and have access to the information to enable them to effectively treat women with PPD as we go forward in terms of Tcp's, what I believe will happen over time is that we'll continue to expand with that first group. They were calling on now broadening to a broader group of <unk>.

Chris Bunecki: In terms of PCPs, what I believe will happen over time is that we'll continue to expand with that first group that we're calling on now broadening to a broader group of PCPs as well as psychs and OBs as we go forward, but that will come in time as well. We'll move to the next question from Brian Abraham with RBC Capital Markets. Please go ahead. Hey, good morning.

<unk> as well as <unk>.

Chris: <unk> in obese as we go forward, but that to come in time as we move forward.

Chris: Okay.

Chris: Well move to the next question from Brian Abrahams with RBC capital markets. Please go ahead.

Brian Abrahams: Congratulations on all the progress and thanks for taking my question. Maybe shifting gears to the pipeline, on 718, can you expand on what you're looking for out of the surveyor study in terms of trends and correlations? And I guess I'm curious how that might influence how you would tweak the dimension study, the size, endpoints, population, or something else, and whether the goal would be for dimension to potentially be registrational for Huntington's. Thanks. Yeah, Brian.

Brian Abrahams: Hey, good morning, Congrats on all the progress and thanks for taking my question, maybe shifting gears to the pipeline on 718 can you expand on what Youre looking for out of the survey or study in terms of trends and correlations.

Brian Abrahams: And I guess I'm curious how that might influence how you would tweak the dimension study size endpoints population or something else and whether the goal would be for dimension to potentially be registrational product. Thanks.

Barry E. Greene: Well, first of all, thanks for the congratulations. We really are excited by the progress, and I congratulate you on sneaking five or six questions into your one question. That was good.

Speaker Change: Yes, Brian.

Speaker Change: First of all thanks for the congratulations we really are excited by the progress and I congratulate you on sneaking five or six questions into your one your one question, though those good I'll turn it over to Laura to talk more about it but before before I do so you're talking about <unk> seven and eight which is our fully owned NMDA positive allosteric modulator that we're studying in <unk>.

Laura Chico: I'll turn it over to Laura to talk more about it, but before I do, I want to talk about DALS and MDOR SAGE 718, which is our fully-owned NMDA-positive allosteric modulator that we're studying in neurodegenerative diseases, and we're excited to have readouts for both Huntington's, Parkinson's, and Alzheimer's this year. Strategically, as we talked about, and Laura will get into specifics, as we've designed the series of Huntington's studies, we did so recognizing that Huntington's is a rare orphan disease. We've done so in a way that if the data are positive, and let me emphasize data matter here, we believe that we have a package to work with regulators on speeding DALS and MDOR to help those suffering from cognitive disorders like Huntington's.

Laura: For degenerative diseases, and we're excited to have Readouts for both Huntington's Parkinson's and Alzheimer's this year strategically as we talked about and Loren will get into the specifics as we've designed the series of Huntington Studies, we've done so recognizing the Huntington's is a rare orphan disease. We've done so in a way that if the data are positive in EMEA.

Laura: Emphasize data matter here that we believe that we have a package to work with regulators on speeding <unk> to help those suffering from cognitive disorders in Huntington's the Parkinsons and Alzheimers are truly phase II studies, where they're learning studies that gives us better support and understanding of designing the phase III, but lori.

Laura Chico: The Parkinson's and Alzheimer's studies are truly phase two studies where they're learning studies. That gives us better support and understanding of designing phase threes, but Laura, do you want to talk more about the dimension and surveyor studies and how they fit together? So, as I mentioned in the introductory remarks, Surveyor is a study that was really designed to serve two purposes. First, to compare the degree of cognitive impairment in patients with Huntington's disease to healthy volunteers.

Laura: Laura you want to talk more about the dimension in surveyor studies and how they fit together sure.

Laura: As I mentioned in the introductory remarks. So there is a study that really was designed to serve two purposes first to compare the degree of cognitive impairment in patients with Huntington's disease, two healthy volunteers and that's important so that we can understand the clinical meaningfulness of that.

Laura Chico: And that's important so that we can understand the clinical meaningfulness of the treatment effect that we're seeing in our studies, both for surveyors and for patients. The second purpose of the study was to evaluate how changes in cognition track with, and this is important to provide supportive evidence, both to regulators and to other stakeholders, about the relationship between these. Of course, when we get the surveyor data, we will look at it very carefully. If there are suggestions in that data that there would be a benefit to changing something in the dimension design, we would do that.

The treatment effect that we see in our both of our survey and dimension.

Laura: The second purpose of this study was to evaluate how changes in cognition.

Laura: Cognition.

Laura: Track with changes in function and this is important to provide supportive evidence both to regulators and to other stakeholders about the relationship between these two metrics.

Laura: Of course, when we get the survey data, we will look at it very carefully if there are suggestions and that data that there would be a benefit to changing something in the dimensions design. We would do that it's important to note that those changes would be limited to ordering of endpoints not changes related to.

Laura Chico: It's important to note that those changes would be limited to the ordering of endpoints, not changes related to, you know, adding new endpoints or doing something that, you know, would really prolong the study. We'll move to our next question from Ami Sadia with Needham & Co. Please go ahead. Hi, this is Purna for AMI.

Laura: Adding new endpoints or doing something that would really prolong the study right.

Laura: Okay.

Laura: We will move to our next question from Amit <unk> with Needham <unk> Company. Please go ahead.

Laura: Hi, This is Amit. Thank you for taking my question.

Purna: Thank you for taking our question. I just had a question about the bridging program. Could you please talk about it and what type of utilization you're seeing of this program? Should we be expecting use of this program as you complete your peer negotiations? I'm not sure I understand the bridging program.

Amit: Just had a question about the <unk> program could you. Please talk about it and what type of utilization you see with this program shouldn't be expecting you participate you competing European negotiation.

Speaker Change: I'm not sure I understood bridging program.

Speaker Change: Yes.

Chris Bunecki: I'm not sure I understand the question. Yeah, patient, patient support. I believe what, what, so, what we said is their Zouve for you is a program that's in place that's largely designed to make sure that we're mitigating patient out of pocket. And we talked about that being able to mitigate the vast majority of these patients that are commercially insured down to a zero dollar out of pocket copay. We also make sure that patients who fundamentally fall in this functionally uninsured group of patients, patients that you would call in other organizations, bridge program patients, are actually able to access the medication. So, we have that resource in place to actually make sure that those patients don't fall through the system, that they can actually get access to the medication. But, as we also said, the vast majority of patients that are flowing through right now are actually covered patients, whether they are commercially insured or Medicaid patients, which, again, is a very good sign or signal from payers around the support that they're providing for women with PPT.

Speaker Change: I'm not sure I understand the question yes.

Speaker Change: Yes patient patient support I believe.

Speaker Change: So what we said is <unk> for you is a program. That's in place that's largely designed to make sure that we're mitigating patient out of pocket and we talked about that being able to mitigate the vast majority of these patients that are commercially insured down to a zero dollar out of pocket co pay we also make sure that patients who fundamentally fallen this functionally uninsured.

Speaker Change: Ah patients patients that you would call in other organizations bridge program patients are actually able to access to medications. So we have that resource in place to actually make sure that those patients don't fall through the system that they can actually get access to the medication, but as we also said the vast majority of patients that are flowing through right now are actually covered patients.

Speaker Change: Whether they are commercially insured or Medicaid patients, which again is a very good sign or signal from payers around the support that they are providing for women with PPD, yes, it's important to keep it keep in mind that.

Barry E. Greene: Yeah, important to keep in mind that, as Chris has mentioned many times, we believe that if a prescription is written for a woman suffering from PPD, we want to make sure that that woman has drugs. So, in our case, it's not really a bridge because it's a 14-day complete course of treatment, not a bridge to chronic medication. We'll move to our next question from Laura Cheekum with Wedbush Security. Go ahead. Hey, good morning, guys. Thanks for the question. I had one on surveyor and dimension and just kind of followed up.

Speaker Change: As Chris has mentioned many times, we believe that if a prescription is written for a women suffer through with you that we want to make sure that that woman heads drugs. So in our case, it's not really a bridge because the 14 day complete course of treatment not a bridge to a chronic medication.

Speaker Change: Well move to our next question from Laura Chico with Wedbush Securities. Please go ahead.

Laura Chico: Hey, good morning, guys. Thanks for the question.

Laura Chico: Had one on surveyor and dimension and just kind of following up I was wondering if you could talk a little bit more about the endpoint and specifically I'm trying to understand well youre using the primary endpoint as the Huntington's cognitive assessment battery I'm trying to better understand how the high Def scale fits in here and I guess.

Laura Chico: I was wondering if you could talk a little bit more about the endpoints. And specifically, I'm trying to understand while you're using the primary endpoint as the Huntington's cognitive assessment battery, I'm trying to better understand how the high-definition scale fits in here. And I guess, Laura, based on your comments, could that become a primary endpoint? Thanks. Laura to answer.

Laura Chico: Based on your comments could that become a primary endpoint.

Yeah.

Speaker Change: Yes. Thanks for the question Laura on Delta named or I'll turn it over to.

Laura Chico: Thank you, Laura. As you noted, HC-CAB is the primary endpoint for the DIMENSION study. We have also included the HI-DEF measure, which is a measure of function, and it's a patient-reported outcome that SAGE has developed specifically for this population. At this point, we will take what we learned from the surveyor study and make a decision about what the proper endpoints should be for dimension, keeping in mind, of course, that the Huntington's Disease Cognitive Assessment Battery is a battery that has been developed by experts in the field to measure domains of cognition that are impacted by,

Laura: Laura answer yes.

Laura: Thank you Laura as you noted the <unk> is the primary endpoint for the dimension study. We have also included the high Def measure, which is a measure of function and its a patient reported outcome that sage has developed specifically for this population, we have developed and validated that measure and.

Laura: Is it it would be appropriate to be in an application to support.

Laura: The efficacy profile of CHF, one eight or dosing them door.

Laura: We at this point, we will take what we learned from the survey or study and make a decision about what the proper endpoints should be for dimension keeping in mind of course that the Huntington's disease cognitive assessment battery is a battery that has been developed by experts in the field to measure demand for cognex.

Laura: That are impacted by.

Barry E. Greene: , and actually reflect some of the domains that we believe Delta and MDoR will impact. So we have no reason to believe that that endpoint will not be appropriate or sufficient, but the high-def is also a good endpoint that will add additional information about how Dalzin-MDoR affects patients. Yeah, and Laura, it's a really great question. As you're well aware, with Down syndrome, we're forging new pathways here. There has not been a medicine specifically approved for cognitive impairment and Huntington's disease.

Laura: Huntington's and actually reflect some of the domains that we believed there was an MTR will improve so we have no reason to believe that that will not be appropriate or sufficient.

Laura: But the high Def is also a good endpoint that will add additional information about how <unk> thousand M door affects patient functioning and lora.

Laura: It's a really great question is as Youre, well aware with Delta under we're forging new pathways here Theres not been a medicine, specifically approved for cognitive impairment and Huntington's disease, It's a really huge unmet need and given the orphan nature.

Nina Botredo-Gardin: It's a really huge unmet need, and given the orphan nature, again, data matters here, but we believe there'll be tremendous flexibility in working with the package here. We'll move to the next question from Nina Botredo-Gardin with Deutsche Bank. Go ahead. Hey, guys, thanks for taking my question. I just want to go back to the Zerzubei launch.

Laura: <unk> data matter here, but we believe there'll be tremendous flexibility in and Youre.

We're working with the package here.

Laura: Okay.

Laura: Well move to the next question from Neena <unk> Garg with Deutsche Bank. Please go ahead.

Neena Garg: Hey, guys. Thanks for taking my question I just wanted to go back to the U K launch.

Barry E. Greene: So just looking at some of the third-party script vendors, so this is Wea Icubia, it looks like there's a decently high capture rate versus what you've reported in terms of dispensed scripts. So I'm just wondering if you can kind of comment on that. And if we should look at those third-party vendors moving forward. And if you can talk at all about what you've been seeing kind of on a week over week perspective on scripts so far this quarter, that'd be great, too. Yeah, Nina, let me start and I'll turn it over to Kimi to talk specifically about IQVIA. So, you know, again, what we reported out in the fourth quarter was roughly 10 days of commercial availability where moms could access healthcare providers to advocate for Zerzube. We're not really talking about the data specifically in January and February, other than the fact that, you know, we're seeing positive trends continue. But Kimi, do you want to talk more about the IQVIA data? Sure. The launch is trackable through IQVIA.

Neena Garg: So just looking at some of the third party script vendors. So this is the way I would caveat. It looks like there is a seasonally high capture rate versus what you reported in terms of defense subscribe. So I'm. Just wondering if you can comment on that and if we should look at those third party vendors moving forward.

Neena Garg: And if you can talk at all about what you've been seeing kind of on a week over week perspective on scripts. So far this quarter that'd be great too. Thanks.

Neena Garg: Yes.

Speaker Change: Let me start I'll turn it over to Kim you talk specifically about <unk>. So again.

Kim: What we've reported out in the fourth quarter was roughly 10 days of commercial availability.

Kim: Their moms could access health care providers to advocate for <unk>, we're not really talking about the data specifically in January February other than the fact that we're seeing positive trends.

Kim: Continue but can you talk more about the acuity data sure the launches trackable through Ikea. However, the data may not provide a complete picture of the utilization what you've seen in the data is shipments to patients not prescriptions and then data does lag by about a week.

Kimi E. Iguchi: However, the data may not provide a complete picture of Zerzube utilization because what you see in the data is shipments to patients, not prescriptions. And the data does lag by about a week.

Kimi E. Iguchi: The data, I'd say, is directionally correct but not precise. There are things like free goods that might not be captured in certain cases, or there might be specialty pharmacies we contract with that might not be covered. So, again, I'd say the data is directionally correct but not precise. We'll move to our next question from George Farmer with Scotiabank. Please go ahead. Hi, good morning.

Kim: The data I would say is directionally correct, but not precise there are things like free goods that might not be captured in certain cases or there might be specialty pharmacies, we contract with it might not be covered so again I'd say the data is directionally correct, but not precise.

Kim: Okay.

Kim: Well move to our next question from George Farmer with Scotiabank. Please go ahead.

George Farmer: Thanks for taking my question. Back, you know, still on the Zerzoubi script, Biogen reported 2 million in sales in December. These guys are reporting 120 square feet, written over the same period, just kind of on the back of the envelope.

George Farmer: Hi, good morning, Thanks for taking my question.

George Farmer: Back to you know it is still on the Zubair scripts Biogen reported $2 million in sales in December and you guys are reporting a 120 scripts.

Speaker Change: <unk> written over the same period, just kind of back of the envelope math suggests that all of those scripts.

Speaker Change: Generated revenue.

Speaker Change: Are we think is that the right way to think about this and maybe you can comment on.

Barry E. Greene: Matt suggests that all those generated by www.sagehealth.org should go into the program as well. Is that the right way to think about it? Yeah, George, I'll take that.

Speaker Change: Whether there are other scripts that didn't get filled.

Speaker Change: And how many perhaps there were some other scripts that were part of the free drug program as well as that is that the right way to think about this.

Barry E. Greene: And thank you for the question. So it's important. Let me reiterate sort of the supply chain, if you will. When specialty pharmas stock the drug, they put an order in, and when that order is sent to the specialty pharma, that's where revenue comes in.

Speaker Change: Yeah, George I'll take that and thank you for the question. So it's important let me, let me reiterate sort of the the supply chain if you will.

Speaker Change: Win with specialty pharma.

Speaker Change: Stock drug they put an order and when that order is sent to the specialty pharma, that's where revenue comes in so revenue is.

Barry E. Greene: So revenue is drug into specialty pharma. The drug gets pulled from specialty pharma when a healthcare provider, and this is done mostly electronically, writes a script. That script automatically goes to specialty pharma, who does insurance verification and other back-end processing. And when all that's done, and it can happen in 24 to 48 hours, that prescription is then shipped to the patient. The IQV data that Kimi talked about are those shipment data, so that's what you can see.

Speaker Change: Drug into specialty pharma.

The drug its toll from substitute pharma with a health care provider and this is done mostly electronically writes a script that script automatically goes to specialty pharma who does it.

Speaker Change: <unk> verification other backend processing.

Speaker Change: All of that is done and it can happen in 24 to 48 hours that prescription then is shipped to the patient the QE data that can be talked about are those shipment data. So that's what you can see we're providing color on script with Jos.

Sumant Kulkarni: We're providing color on script, which, as Chris mentioned, we'll provide for the first couple quarters, but likely we'll drop that metric. So it's not a direct correlation. Now, the fact that we saw 120 scripts is exciting and encouraging in a very short period of time in December. We'll move to our next question from Sumant Kulkarni with Canaccord Genuity. Please go ahead. Good morning.

Speaker Change: Chris mentioned will provide for the first couple of quarters, but likely will drop that that metrics. So it's not a direct correlation no.

Speaker Change: The fact that we.

Speaker Change: We saw 120 scripts is exciting and encouraging in a very short period of time in December.

Speaker Change: Well move to our next question from Cmos Kulkarni with Canaccord Genuity. Please go ahead good morning.

Barry E. Greene: Thanks for taking my question. Now that you've probably had some patients finish their 14-day course of therapy, what sort of real-world feedback are you getting from patients on how quickly Zazue may be working in the real world and how patients might be feeling after the treatment, and if there are any unexpected positives or negatives we've seen post-dosing? Yes, Sumant, great question. So the early feedback we've heard from the field is positive, and we're highly encouraged by the anecdotes of early patient success stories. Of course, you know, a bunch of anecdotes don't add up to data.

Sumant Kulkarni: Thanks for taking my question now that you've probably had some patients finished their 14 day course of therapy, what sort of real world feedback are you getting from patients on how quickly those who may be working at the railway and basis might be feeling after the treatment and if there are any unexpected positives or negatives you've seen post dosing.

Speaker Change: Yes sure Great question. So the early feedback we've heard from the field to positive and we're highly encouraged by the anecdotes of the early patients successors of course.

Speaker Change: Bunch of anecdotes.

Speaker Change: Add up to data.

Barry E. Greene: We're also pleased that we're hearing back from many healthcare providers, including OB-GYNs, primary care, and psychiatric care, about Zerzube. And in general, what we can say is that in the real world, Zerzube is performing as we saw in clinical trials, and that it is taken at night, rapid onset of abstinence, 50 mg is being prescribed, and patients are completing their 14

Speaker Change: We're also pleased that we are hearing back from <unk>.

Speaker Change: Many health care providers, including <unk> primary care and sites about bulk zubaie and in general what we can say is in the real world <unk> performing as we saw in clinical trials and that is taken at night rapid onset of actions 50 milligram is being prescribed and patients are completing the 14 day short course.

Speaker Change: <unk>.

Speaker Change: Thanks.

Operator: Thank you. We'll move to our next question from Akash Tewari with Jeffrey. Please go ahead. Hi, this is Phoebe on behalf of Akash.

Speaker Change: Thank you.

Speaker Change: Well move to our next question from a cash tomorrow with Jefferies. Please go ahead.

Speaker Change: Hi, This is Steven on for Kash. Thank you for taking our question.

Phoebe: Thank you for taking our question. Biogen mentioned on their Q4 call yesterday that they aren't sure if the initial set of prescriptions represent the bolus, given that the study was approved in August and then only launched in December. So do you feel like demand may be a bit choppy out of the gate, and has there been, or hasn't there been, any increased demand in January?

Steven: Biogen mentioned on the Q4 call yesterday that they arent sure a famous one initial prescriptions represents a boneless given that <unk> was approved in August and then only launched in December. So do you feel like demand may be a bit choppy out of the gate and has there been or has there been any increased demand in January.

Barry E. Greene: Additionally, just wondering why you didn't guide for the Survey of Reps for 2024 and do you plan to guide in later years? Thank you. Yeah, Phoebe, thanks for the couple of questions. I'll start. I'll ask Chris to comment more, and then Kimi can talk about guidance.

Steven: Additionally, just wondering why you didn't guide to just I may have asked for 'twenty 'twenty four and do you plan to guide in later quarter. Thank you.

Speaker Change: Yeah Savi. Thanks for the couple questions I'll start I'll ask Chris to comment more than and then Tim you can talk about guidance. So.

Chris Bunecki: So the TPD is not a warehousing effect type disease; we're seeing tremendous demand continue into the early part of 2024. So we can confidently say there's no warehousing here. We're seeing demand continue. And the numbers, you know, while encouraging, are really small relative to the half a million women a year potentially suffering from TPD. So there's a long way to go to help many of

Speaker Change: The TB TBD is not a warehousing effect type disease, we're seeing tremendous demand continue into the early part of 2024. So we can constantly say theres no warehousing here, we're seeing demand continue in the numbers, while encouraging a really small relative to the half a million women a year potentially suffering from PPD. So it is a.

Barry E. Greene: Chris, you want to talk about the early launch dynamic, and then maybe Kimi can talk about guidance. So what we're hearing from clinicians out of the gate, and Barry touched on it in his opening remarks, we're seeing strong, positive performance coming from Zerzuvia in and around prescriptions, prescribing patterns, patient support, and coverage. Those are all areas that we've talked about significantly. But again, specifically around physician utilization of the medication, we're seeing balanced prescribing across physician types, OBGYNs, and psychiatrists with a core group of PCPs that are also writing this medication as well. Those are clinicians that actually have women in front of them that are presenting at the moment with the signs and symptoms of TPD.

Speaker Change: Long way to go top many of these women Chris you want to talk about through the early once dynamic and then maybe Kevin can talk about guidance.

Speaker Change: What we're hearing from clinicians out of the gate and Barry touched on in his opening remarks, we're seeing strong positive performance coming from Zubaie in and around prescriptions prescribing patterns patient support and coverage and those are all areas that we've talked about significantly, but again, specifically around physician utilization of the medication, we're seeing balanced prescribing.

Speaker Change: Across physician types, Obgyns and psychiatrist with a core group of Pcbs that are also writing this medication as well too.

Speaker Change: Those clinicians that actually have women in front of them that are presenting in the moment with the signs and symptoms of PPD. These are not patients that have been waiting for the medication for a sustained period of time as you might see in other categories. So we really believe here and as Barry said that this is a category where there is not warehousing effect and we're going to continue to make sure that we do all that we can through our <unk>.

Chris Bunecki: These are not patients that have been waiting for the medication for a sustained period of time, as you might see in other categories. So we really believe here, and as Barry said, that this is a category where there is no warehousing effect, and we're going to continue to make sure that we do all that we can through our sales organization and through our omnichannel efforts, and particularly digital, to provide physicians with the education, the information, and the support to prescribe Zerzuvia at the moment when these women come through their offices. Yeah, and before Kimmy jumps in with guidance, Phoebe, let me highlight something that Chris said earlier.

Speaker Change: <unk> organization and through our omni channel efforts, and particularly digital to provide physicians with the education of the information and the support the prescribed zubaie in the moment when these women come through their offices.

Speaker Change: Before kidney jumps in with guidance, let me let me, let me highlight Chris said earlier on.

Barry E. Greene: We're early in the launch, but we've already seen the paradigm shift from a health care provider suspecting depression and referring to a health care provider diagnosing and treating depression. We're really in the launch phase, and that's already a paradigm shift we're seeing among these health care providers prescribing. That's highly encouraging. On revenue guidance, to start with, we're pleased about the encouraging early launch of Zerzuvia, as you heard on our call. But we believe we need to take some additional time to better understand the dynamics around the update. We plan to communicate additional updates related to the commercial launch of Zizouvé in due course.

We're early in the launch, but we've already seen the paradigm shift from a health care provider, suspecting depression, and referring to health care providers, diagnosing and treating where really you're in launch. So that's already a paradigm shift we're seeing among these health care providers prescribing that's highly encouraging.

Speaker Change: On the revenue guidance to start with we're pleased about the encouraging early launch of <unk> as you've heard from our call, but we believe we need to take some additional time to better understand the dynamics around the uptake we plan to communicate additional updates related to the commercial of the zoo. They in due course.

Kimi E. Iguchi: We'll move to the next question from Yatin Suneja with Guggenheim. Please go ahead, www.sagehealth.com. Thank you for taking the question. Specifically, in precedent studies, the primary endpoint is the Weschler Intelligence Scale. Could you help us understand how, like what is the relevance of this scale, number one?

Speaker Change: Okay.

Speaker Change: I'll move to the next question from yacht in Senegal with Guggenheim. Please go ahead.

Speaker Change: Yes.

Yacht: Thank you for taking the question specifically on the precedent study. So the primary endpoint is to do better.

Intelligence scale.

Yacht: Could you help us understand how what is the relevance of this scale number one what do we see from a placebo perspective.

Yatin Suneja: What do we see from a placebo perspective for this study? I understand, you know, maybe you're not willing to go there and tell us what data you would like to see, but just help us understand how placebo performs on this scale so that we have a database. Thanks for the question on Dalton M. Doerr and the precedent study. Laura, do you want to take that?

Speaker Change: For the study I understand.

Speaker Change: Maybe youre not willing to go there and then tell us what data you would like to see but just help us understand how placebo perform under scale. So that you have.

Speaker Change: He is a baseline thanks.

Hey, guys. Thanks for the question on <unk> and the precedent study Laura you want to take that sure.

Laura Chico: Sure. In the precedent study, we included the WAIS-IV coding as a primary endpoint based on information we had gotten earlier in our development program for Delsin-MDOR. As I mentioned earlier, in the Delsin-MDOR program, we conducted small probe studies in Alzheimer's, Parkinson's, and Huntington's, and in each of those studies, we saw signals of efficacy in cognitive domains of executive function and learning and memory.

Speaker Change: With the precedent study we included the waste for coding as a primary endpoint based on information we had gotten earlier in our development program for <unk> as I mentioned earlier in the <unk> program. We conducted small probe studies in Alzheimer's, Parkinson's and Huntington's disease and in each of those.

Speaker Change: Studies, we saw signals of efficacy and cutting the domains of executive function and learning and memory.

Laura Chico: And the WAIS-IV coding was a scale that we used in those early studies to detect that treatment. So, what we are doing now in the precedent study is using that as a primary measure. Recognizing, of course, that it is not clear whether that could be. The study also includes a number of other measures of cognition, including the MOCA and the SCOPA COG.

Speaker Change: And the waste for coding was a scale that we use in those early studies to detect that treatment difference. So what we are doing now and the precedent study is using that as a primary endpoint recognizing of course that it is not clear whether that could be.

Speaker Change: Endpoint. So the study also includes a number of other measures of cognition, including the Moca and the scope at heart and so we will be looking at directional effects on those endpoints to make decisions about moving forward.

Laura Chico: And so, we will be looking at directional effects on those endpoints to make decisions about whether or not to treat. Laura, if I can add just one thing, I think across all these studies, it's important to recognize that we are looking for an improvement from baseline, not necessarily a slowing of change. And I think that will also factor into how we look at the differences versus placebo. We'll move to the next question from Vikram Purohit with Morgan Stanley. Go ahead. Hi, good morning.

Speaker Change: And Laura if I could add just one thing I think across all of these studies, it's important to recognize that we were looking for an improvement from baseline.

Speaker Change: Certainly a slowing of change and I think that will also factor into how we look at.

Speaker Change: The differences versus placebo.

Speaker Change: Yeah.

Speaker Change: We will move to the next question from Vikram <unk> with Morgan Stanley. Please go ahead.

Vikram Purohit: Thanks for taking our question. We had one follow-up on your initial reading of prescribing behavior. So I believe you mentioned in your opening remarks that there were certain providers who wrote multiple prescriptions for Aziruze in the first 10 days of the launch. So we were wondering if there are any common characteristics across these providers or their patient bases that stick out to you.

Vikram: Hi, Good morning, Thanks for taking our question we had one follow up on your initial read of prescribing behavior. So I believe you mentioned in your opening remarks that there were certain providers who had written.

Vikram: Multiple prescriptions preserving the first 10 days of the launch. So we were wondering if there are any commentary for sticks across these providers.

Speaker Change: Or their patient basis that stick out to you and more generally if this gives you a read on how concentrated or not the prescriber base for us usually there could be throughout 2024. Thank you.

Barry E. Greene: And more generally, if this gives you a read on how concentrated or not the prescriber base for Aziruze could be throughout 2024. Thank you. Yeah, thanks for the question. I'll take that. I'll ask Chris to add some additional color if there's any additional color.

Speaker Change: Yeah. Thanks for the question.

Speaker Change: I'll take that I'll ask Chris to add if there is any additional color. So we're actually seeing broad prescribing across the United States.

Chris Bunecki: So we're actually seeing broad prescribing across the United States, among, as we said, psychiatry, OB-GYNs, and, you know, small numbers, but primary care. I don't know that there are trends that are indicative of multiple prescribers other than a prescriber that we assume had a positive experience sees another patient suffering from PPD and believes that Zizouve is the right drug to reach for As you know, our goal is for Zizouve to be the first-line treatment for women suffering from PPD, and we're excited and encouraged by the early progress to date. Now, we'll move to our next question from Marc Goodman with Lyrinc. Please go ahead. Yes, good morning. Two questions.

Speaker Change: As we said psychiatry Ob gyn and in.

Speaker Change: Small numbers, but primary care.

Speaker Change: Though that there is trends that are indicative of multi prescribers other than a prescriber that we assume had a positive experience sees another patient suffering from PPD and believes that <unk> has the right drug to reach four as you know our goal is for <unk> to be the first line treatment for women suffering from PPD.

Speaker Change: We're excited and encouraged by the early progress to date.

Speaker Change: Well move to our next question from Marc Goodman with Leerink. Please go ahead.

Marc Goodman: First, for 324, can you remind us how long the drug is active such that taking it at night will still have activity throughout the next day? And then, just on 718, can you talk about the rationale for using oxysterol in Parkinson's? I understand that Huntington's patients have low levels, but I didn't understand why it makes sense in Parkinson's.

Marc Goodman: Yes. Good morning, two questions first for three to four can you remind us how long the drug is active such that taking at night will still have activity throughout the next day and then a question just on 718.

Marc Goodman: Could you talk about the rationale for using the oxy sterile and Parkinsons I understand the huntington's patients have low levels, but but I didn't understand why it makes sense in Parkinson's.

Barry E. Greene: Thanks. Yeah, I'll quickly take the SAGE 324 question and ask Mike to comment on 718. So, the half-life of 324 is sufficient for coverage when taken at night for the next day. You know, we're not worried about that.

Speaker Change: Yeah, I'll quickly take the phase III for question ask Mike to comment on the.

Speaker Change: On civil and eight so.

Speaker Change: The half life of three to four is sufficient for coverage when taken at night for the next day, we're not worried about that.

Mike Quirk: We believe that the drug effect will last for, you know, multiple days, actually. So, we're really trying to get to a steady blood serum level that translates to a steady level in the brain. Mike, do you want to talk about SAGE 718? Yes, and I think the point when we're thinking about SAGE 718 and its role as a modulator of NMDA receptors is, while we gained insight from the endogenous modulator 24S hydroxycholesterol, we've also done quite a bit of work with SAGE 718 and other similar molecules that we've worked on to show that it does not require there to They work in different ways to impact NMDA receptor function. So, we've been able to show that if you have hypofunction due to a genetic change, a pharmacological change, any way that you have a loss of NMDA receptor function, you can rescue those deficits with molecules such as SAGE 718.

Speaker Change: We believe that.

Mike: The drug effect will last.

Mike: Multiple days actually so really trying to get to a steady blood serum level that translate to a steady level in the brain.

Mike: If you're talking about seats of one eight yes.

Mike: I think the point when we're thinking about Sage 718 in his role as a modulator of NMDA receptors as while we gained insight from the endogenous modulator twenty-four us hydroxy cholesterol. We've also done quite a bit of work with save some money and other similar molecules that we've worked on to show that it does not require there could be low levels of 'twenty for us per se.

Mike: So I wont, even some of our molecules to work they work on different ways of impacting NMDA receptor function. So we've been able to show that if you have hypofunction due to a genetic change a pharmacological change any way that you have a loss of NMDA receptor.

Mike: Function you can rescue those deficits with molecules such as Sage I'm wondering so in the context of Parkinsons and Alzheimers.

Mike Quirk: So, in the context of Parkinson's, Alzheimer's... www.sagetherapy.com. Thank you. That will conclude the Q&A portion of today's call. With that, I will turn it back over to Mr. Greene for closing remarks. Thanks, Taryn, and thanks, everyone, for joining us this morning to review our results from the fourth quarter and full year 2023. As we look ahead to the ongoing launch of ZUZUVE and enter a catalyst-rich 2024 with multiple data readouts expected, I'm highly confident that we're making important progress to deliver on our mission to develop and launch life-changing brain health medicines so every person can thrive. Thanks again, everyone, and have a great day. This concludes today's call. Thank you again for your participation. You may now disconnect and have a great day! www.SAGE.org

Mike: Believe that there is a strong rationale for NMDA receptor dysfunction, even if the proximal mechanism is not related to oxy sterile changes per se and again, that's why we've designed to seven when a program to look at different patient populations, where we think that there's an underlying cause of NMDA receptor impairment, regardless of the specific mechanism driving that change.

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

Barry E. Greene: Thanks, Darren and thanks, everyone for joining us this morning to review our results for the fourth quarter and full year 2023 as.

Barry E. Greene: As we look ahead to the ongoing launch of <unk> and enter a catalyst rich 2024 with multiple data readouts expected I'm highly confident that we're making important progress to deliver on our mission to develop and launch life changing brain health medicines. So every person can thrive. Thanks again, everyone and have a great day.

Speaker Change: This concludes today's call. Thank you again for your participation you may now disconnect and have a great day.

Speaker Change: Yes.

Speaker Change: Yeah.