Q4 2019 Earnings Call

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Operator: Good morning. Welcome to SAGE Therapeutics' fourth quarter and year-end 2019 financial results conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of SAGE's website at sagerx.com. This call is the property of SAGE Therapeutics, and recording, reproduction, or transmission of this call without the express written consent of SAGE Therapeutics is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Matthew Callistri, Investor Relations at SAGE.

Matthew Callistri: Hello, and thank you for joining SAGE Therapeutics' fourth quarter and year-end 2019 financial results conference call. Before we begin, I encourage everyone to go to the Investors & Media section of our website at sagerx.com.

Matthew Callistri: Where you can find the press release related to today's call as well as the slides that contain supplemental details. I would like to point out that we...

Good morning, welcome to stage Therapeutics fourth quarter and year end 2019 financial results Conference call.

Currently all participants I not listen only mode. This call is being webcast live on investors and media section. That's they just website at stage, our ex Dot com.

Matthew Callistri: Please consult 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 Dr. Jeff Jonas, our Chief Executive Officer; Mike Clunan, our Chief Business Officer; and Kimi Iguchi, our Chief Financial Officer. We will be joined for the Q&A session of the call by Dr. Steve Kaines, our Chief Medical Officer, and Dr. Jim Doherty, our Chief Research Officer. I will now turn the call over to Jeff.

This call. This a copy of Sage therapeutics and recording reproduction or transmission of this call without the expressed written consent assays therapeutics is strictly prohibited.

Please note that this call is being recorded.

I would now like to introduce meticulous chief Investor Relations that's age.

Jeff Jonas: Thanks, Matt. Good morning, and thanks, everybody, for joining us. We're pleased to update you today on our mission to bring medicines that matter to people with brain health. This morning, I'll provide an overview of our 2019 fourth quarter and full year progress, including advancements across our depression, neuropsych, and neurology franchises. Then Mike will take a deep dive into the Soreso launch metrics, and lastly, Kimi will provide an update on financial. In the last several years, SAGE achieved a track record of success in an area of science known to have an unusual amount of failure. Our success, we believe, was a result of our unconventional thinking and creative problems.

Hello, and thank you for joining Sage therapeutics fourth quarter and year end 2019 financial results conference call before we begin I encourage everyone to go to the investors and media section of our website at <unk>.

Alright, Dot com, where you can find the press release related to today's call as well as the slides it contains supplemental details.

I would like to point out that we will be making forward looking statements, which are based on our current expectations and believes these statements are subject to certain risks and uncertainties and our actual results may differ materially. Please consult the risk factors discussed in today's press release, Andean are actually see filings for additional details.

Jeff Jonas: That being said, the Mountain Trial with SAGE 217 reminds us all that drug development at its core is difficult, and that innovation in the brain health space is not always straightforward. As we consider the Mountain data, along with the bulk of the available clinical data for xeranlone, we believe it is clear that this is an active drug, having completed two positive pivotal trials with tremendous potential for the treatment of This is what drug development looks like. We learn, we adjust, and then we progress.

We will begin the call with prepared remarks by Dr., Jeff Jones, Our Chief Executive Officer, Mike Cronin, our Chief business Officer, and Kimi Iguchi, our Chief Financial Officer will be joining for the June recession of call by Dr., Steve Kean, Our Chief Medical Officer, Dr., Jim Doherty, Our Chief Research Officer, I'll now turn the call over to Jeff.

Thanks, Matt Good morning, Thanks, everybody for joining us we're pleased to update you today, our mission to bring medicines that matter to people that greenhill disorders. This morning, I'll provide an overview of our 2019 fourth quarter full year progress, including advancements across our depression neuroscience neurology franchises.

Jeff Jonas: Let me turn first to a discussion of the depression framework. While the mountain trial with seranolone did not meet its primary endpoint at day 15, the effect size achieved within days was overall, particularly in light of comparison to the effects seen with the current standards of care. We believe the data support our hypothesis that seratolone has a differentiated profile with the potential for a rapid and robust onset with durable effects. We previously stated we would meet with the FDA in the first quarter. Our goal is to find the most efficient pathway that brings Zaranulone to patients as quickly as possible. We will not speculate on potential scenarios, and we will announce next steps for Zaranulone and the Landscape Program once we evaluate the advice from our first quarter meeting with the FDA, including receipt of the meeting. Michael will take a deep dive on Rosalresso, but let me quickly highlight three key areas where we have achieved progress since the launch. First, underlying patient demand is strong. Second, HCPs are diagnosing and referring patients for treatment. And third, payer coverage is exceeding expectations.

Then Mike will take a deep dive into the though so Russell launch metrics and lastly, kimmy will provide an update on financials.

In the last several years Sage achieved the track record of success in an area of science known to have an unusual amount of failure and disappointment.

Our success, we believe was a result of our unconventional thinking and create a problem solved.

That being said the mountain trial with Sage 207 reminds us all that drug development at its core is difficult.

And that innovation in the brain health space is not always straightforward as we consider the mountain data along with the bulk of the available clinical data because ran alone. We believe it is clear that this is an active drug having completed two positive pivotal trials with tremendous potential for the treatment of major depression.

What drug development looks like we learn we adjust and then we progress let me turn first to a discussion of the depression franchise, while the mountain trial with Serrano did not meet its primary endpoint. A day 15, you exercise achieved within days was noteworthy, particularly in light of comparison to the effects seen with the current standards of care.

Jeff Jonas: Later in the call, Mike will provide more detail on the positive... Turning now to our neurology franchise with SAGE 324, our next GABA PAM. Earlier in 2019, we announced positive results from an open-label, single-dose study with SAGE 324 in essential tremor. This condition is the most common movement disorder in the U.S. and affects an estimated 6 million people in the U.S. alone.

We believe the data support a hypothesis that is around alone has a differentiated profile with the potential for a rapid and robust onset with durable effect.

We previously stated we would meet with the FDA in the first quarter.

Our goal is to find the most efficient pathway to brings around onto patients as quickly as possible.

We will not speculate on potential scenarios and we will announce next steps for is around alone and the landscape program. Once we evaluate the advice from our first quarter meeting with the FDA, including receipt of the meeting minutes.

Jeff Jonas: What this open-label study has shown us so far is that SAGE 324 is a compound with the pharmacologic characteristics we believe are well suited for development opportunities, not only in essential tremor but also in epilepsy and Parkinson's. Our first step in advancing this novel compound is initiating a Phase II trial in central tremor. We are on track to begin this trial with a dose of 60 mg during the first half of 2020. We've also made progress with the lead asset in our neuropsych franchise, SAGE 718. We recently completed our Phase 1 program in healthy volunteers and in patients with hunting diseases. In an open-label study, SAGE 718 at 1 mg was well-tolerated, and patients demonstrated improved performance compared to baseline on an assessment of executive function.

Michael take a deep dive on Rosebel recipe, but let me quickly highlight three key areas, where we have achieved progress since the launch.

First underlying patient demand is strong second HCP is our diagnosing and referring for treatment at third payer coverage is exceeding expectations.

Later in the call Mike will provide more detail on the positive indicators.

Turning now to our neurology franchise and stage 324, our next got a pan.

Earlier in 2019, we announced positive results from an open label single dose study with stage 324, and essential tremor. This condition is the most common movement disorder in the U.S. and affects an estimated 6 million people in the U.S. alone.

What this open label study has shown us so far is I'd say Street 24 is a compound with the pharmacologic characteristics. We believe are well suited for development opportunities not only in essential tremor, but also in epilepsy and Parkinson's disease.

Jeff Jonas: These data align with our expectations of this molecule and are relevant to multiple disorders with impaired cognition, including Huntington's, Alzheimer's, and Parkinson's. We are further interrogating these data to inform the advancement of SAGE 718 into one or more Phase 2a open-label studies evaluating diseases in patients with impaired cognitive function. Results from these studies will inform the plan for advancement of SAGE 718 into further Phase 2 development, including hunting. We've also expanded our early-stage pipeline with two additional proprietary assets, both of which now have an open IND. SAGE 904, our second novel NMDA product candidate, is currently being evaluated in a Phase I trial in Healthy Volunteers as a potential oral therapy for disorders involving NMDA hypofunction. Additionally, we are evaluating plans to advance SAGE 689, an intramuscular GABA-PAM, into the clinic as a potential therapy for disorders associated with GABA hypofunction.

My first step in advancing this novel compounds is initiating a phase two trial in essential tremor. We are on track to begin this trial with it does 60 milligrams during the first half of 2020.

We've also made progress with the lead acid and under a site franchise Sage 7.8, we recently completed a phase one program in healthy volunteers in patients with Huntingtons disease.

In an open label studies Sage 7.81 milligram was well tolerated and patients demonstrated improved performance compared to baseline on assessments about executive functioning.

These data aligned with our expectation is up this molecule and irrelevant to multiple disorders, where the pad cognition, including Huntingtons, Alzheimer's and Parkinson's disease.

We are further interrogating these data to inform the advancement of Sage 7.8 into one or more phase two way open label studies evaluating disorders in patients with impaired kind of function results of these studies will form the plan for advancement of Sage 7.8, it to further base your development, including Huntingtons disease.

We've also expanded our early stage pipeline with two additional proprietary assets both of which now have over 90 days.

Page nine <unk> for our second novel NMT, a product candidate is currently being evaluated in a phase one trial in healthy volunteers as a potential oral therapy, but disorders involving and M.D.A. hypofunction.

Jeff Jonas: As a company, SAGE has made a decision to develop new drugs for the treatment of brain health disorders. We've taken an approach to drug discovery and development that we think is unique and is now being replicated by others. We believe the potential of our pipeline of novel compounds is unmatched in neuroscience. Now, I'll turn the call over to Mike to provide additional details about the launch.

Additionally, we are evaluating plan to advance Sage 689, and intramuscular GABAA Pam entered the clinic hasn't been central therapy for disorders associated with GABAA hypo function.

As a company Sage has made a decision to develop new drugs for the treatment of brain health disorders. We've taken an approach to drug discovery and development that we think is unique and is now being replicated by others.

Mike: Thanks, Jeff. And good morning, everyone.

Mike: We are now two quarters into the launch and remain encouraged by the measurable forward momentum. And while the indicators are strong, as we have always said, breaking through on the predominantly hospital-based launch of Xoreso and the lack of urgency to treat this medical condition that sits at the intersection of women's and mental health is a challenge requiring time to solve. For the quarter, we recognized product revenue of $2 million, which is a 33% increase over Q3. Full year 2019 revenue since launch was $4 million.

We believe the potential of our pipeline of novel compounds is unmatched in the neuroscience space.

And now I'll turn the call over to Mike to provide additional details about the watch.

Thanks, Jeff and good morning, everyone. We're now two quarters into the launch and remain encouraged by the measurable forward momentum and while the indicators are strong as we've always said breaking through on the predominantly hospital based launches arrest, though and the lack of urgency to treat for this medical condition that sits at the intersection of women's and mental.

Health is a challenge requiring time to solve for the quarter, we recognize product revenue of 2 million, which is a 33% increase over Q3 full year 2019 revenue since launch was 4 million.

Mike: Similar to the fourth quarter, we are anticipating modest revenue growth over the next couple of quarters. We expect an increase in revenue growth rate in the second half of 2020 based on our plans to increase the number of treatment sites, specifically larger hospitals, and drive increased volume at current sites of care. To drive revenue growth and increase patient access, our strategy in 2020 will continue to focus on increasing the number of sites that are treatment ready, increasing PPD patient demand, and treatment volume in geographies where there are treating sites of care through focused deployment of our resources. Leveraging strong payer coverage and access, while increasing confidence in the reimbursement pathway, increasing the breadth and depth of HCP referrals, and supporting patients, HCPs, and sites of care through SAGE Central. In the fourth quarter, there was improvement in all key metrics, as our deliberate and focused approach continues to make progress. Let me elaborate further.

Similar to the fourth quarter, we are anticipating modest revenue growth over the next couple of quarters. We expect an increase in the revenue growth rate in the second half of 2020 based in our plans to increase the number of treating sites, specifically larger hospitals and drive increased volume at current sites of care.

To drive revenue growth and increased patient access our strategy in 2020, well continue to focus on increasing the number of sites that are treatment ready.

Increasing PPD patient demand and treatment volume in geographies, where there are treating sites of care through focus deployment of our resources.

Leveraging strong payer coverage in access while increasing confidence in the reimbursement pathway.

Increasing the breadth and depth of HCP referrals, and supporting patients HCP and sites of care through safe central.

In the fourth quarter, there was improvement in all key metrics as our deliberate and focused approach continues to make progress. Let me elaborate further we had 300 additional start forms in the fourth quarter, a 50% increase from Q3, bringing the total since the launch to more than 500, we also doubled the number of referring HCPCS to more than 300.

Mike: We had 300 additional start forms in the fourth quarter, a 50% increase from Q3, bringing the total since the launch to more than 500. We also doubled the number of referring HCPs to more than 300. From a site activation perspective, we ended the year with more than 175 REMS-certified sites of care, compared to more than 140 as of Q3. We expect REMS-certified sites to become less of a forward indicator in the future, with treating sites of care being the more important metric to drive revenue. We've made progress activating treating sites of care, with 29 sites having infused Xoreso as of the end of the fourth quarter, nearly triple the number for Q3. However, we have learned that it takes more time than anticipated to activate sites of care, especially larger institutions.

From a site activation perspective, we ended the year with more than 175, Rems certified sites of care compared to the more than 140 as of Q3, we expect rems certified sites to become less of a forward indicator in the future with treating sites of care being the more important metric to drive revenue.

We've made progress activating treating sites of care with 29 sites, having infused moreso as of the ended the fourth quarter nearly tripled the number for Q3.

We have learned that it takes more time than anticipated activated sites of care, especially the larger institutions. However, we continue to see positive momentum at larger sites as they move closer to becoming treatment ready.

Mike: However, we continue to see positive momentum at larger sites as they move closer to becoming treatment ready. We have also seen positive dynamics in payer coverage. At the end of the fourth quarter, 80% of total covered lives have favorable coverage, meaning no or limited restrictions, and SAGE Central continues to be a valued resource for PPD patients, HCPs, and sites of care, with more than 95% of patients utilizing our patient support. As I mentioned on our third quarter call, and perhaps most importantly, we continue hearing stories from moms who have been treated, many who are seeing major benefits. "I finally feel like myself again," is a comment we hear often.

We've also seen positive dynamics in payer coverage at the ended the fourth quarter, 80% of total covered lives have favorable coverage that is no or limited restrictions and safe central continues to be a valued resource for PPD patients HCP and sites of care with more than 95% of patients utilizing our piece.

In support.

As I mentioned on our third quarter call and perhaps most importantly, we continue hearing stories from moms, who have been treated many who are seeing major benefits I. Finally feel like myself again is a comment we hear Austin.

We now have a full six months of learnings from this first of its kind launch based on these learnings. We are taking several steps. We believe will help us achieve accelerated revenue growth in the second half of the year.

Mike: We now have a full six months of learnings from this first-of-its-kind launch. Based on these learnings, we are taking several steps we believe will help us achieve accelerated revenue growth in the second half of the year. Specifically, we have seen that internal complexities of creating new protocols, operationalizing the REMS, and identifying pathways to reimbursement have been barriers to patient access, especially in larger hospitals and health care systems. We now expect it could take more than nine months for the majority of sites that want to treat patients with Xoreso to become activated, and larger hospitals could take 12 months or longer to activate.

Specifically, we have seen that internal complexities of creating do protocols operationalizing, the rems and identifying pathways to reimbursement have been barriers to patient access, especially in larger hospitals and health care systems. We now expect it could take more than nine months for the majority of sites that want to treat was the rest of to become activated.

And larger hospitals could take 12 months or longer to activate.

To accelerate the site readiness, we are sharing best practices from successful site activations, providing tools supporting peer to peer education, and leveraging sage central to support hospital administrations efforts to accelerate the steps to becoming treatment ready.

Mike: To accelerate site readiness, we are sharing best practices from successful site activations, providing tools, supporting peer-to-peer education, and leveraging SAGE Central to support hospital administration's efforts to accelerate the steps to becoming treatment ready. Enabling the treatment readiness of large hospitals will be critical to meet the growing demand and our expectations for Xeresso and to support all patient types, both Medicaid and commercial. Despite securing broad and favorable coverage for Xoreso, sites are still often required to negotiate reimbursement amounts with individual payers under commercial coverage. Sites of care want direct reimbursement experience after infusing a patient, and it can take time to receive payment from payers. What this means is some sites are becoming treatment ready, administering treatment to one or two women, but then pausing to wait and evaluate reimbursement outcomes. This treatment pattern has led to a lag between site activation and revenue.

Enabling the treatment readiness of large hospitals will be critical to meet the growing demand and our expectations for moreso and in supporting all patient types, both Medicaid and commercial.

Despite securing broad and favorable coverage for the rest. So sites are still often required to negotiate reimbursement amounts with individual payers under commercial coverage sites of care want to reps reimbursement experience after infusing a patient and it can take time to receive payment from payers. What this means is some sites are becoming treatment ready.

Administering to one or two women, but then pausing to beat and evaluate reimbursement outcomes. This treating pattern has led to a lag between site activation and revenue. Our team is focused on sharing successful reimbursement learnings from a number of active sites help new and potential sites become more confident in the process.

Mike: Our team is focused on sharing successful reimbursement learnings from a number of active sites to help new and potential sites become more confident in the process. With approximately 50% of the PPD population being covered by Medicaid, we are also focused on improving access for these women. Medicaid reimbursement varies state-by-state and often depends on whether the state treats the Xeresco infusion as an inpatient or outpatient administration.

With approximately 50% of the PPD population being covered by Medicaid. We're also focused on improving access for these women.

Medicaid reimbursement very state by state and often depends on whether the state treats the rest of confusion as an inpatient or outpatient administration.

Through our efforts we are seeing positive progress we were granted a C code in January which provides hospitals and easier pathway to reimbursement in an outpatient setting the c-code is being adopted by commercial and state Medicaid plans and we anticipate activation by the end of the first quarter 2020, which could improve the reimbursement transparency.

Mike: Through our efforts, we are seeing positive progress. We were granted a C-code in January, which provides hospitals an easier pathway to reimbursement in an outpatient setting. The C-code is being adopted by commercial and state Medicaid plans, and we anticipate activation by the end of the first quarter of 2020, which could improve reimbursement transparency. In closing, the indicators of success continue to be positive. We are leveraging learnings, and we are focused on increasing patient access by increasing the number of treatment sites of care, including larger hospitals. This is a unique launch in some very specific ways. Introducing the first ever healthcare facility-based 60-hour continuous treatment for postpartum depression requires a high level of initial effort from several stakeholders, within and outside each side of care. We are not just introducing an innovative treatment; we are establishing an entirely new treatment protocol in a system that is not necessarily designed for flexibility. And now, I'll turn the call over to Kimi to review our finances.

In closing the indicators of success continue to be positive, we're leveraging learnings and we are focused on increasing patient access by increasing the number of treating sites of care, including larger hospitals. This is a unique launch in some very specific ways introducing the first ever health care facility based 60 hour continuous treatment.

For postpartum depression requires a high level of initial effort from several stakeholders within and outside each site of care. We're not just introducing an innovative treatment. We are establishing an entirely new treatment protocol in a system that is not necessarily designed for flexibility and now I'll turn the call over to kill me to review our financial.

Thanks, Mike 29 came with a transformative year for stage, we received approval for the first ever treatment for postpartum depression, an important step in the treatment of within health net.

Kimi E. Iguchi: Thanks Mike. 2019 was a transformative year for SAGE. We received approval for the first ever treatment for postpartum depression, an important step in the treatment of women's health and mental health. RESSEL's approval was also an important step for SAGE, marking our transition to commercialization. This year we grew our workforce to support our commercial launch and the infrastructure to succeed as a commercial company with an expanding portfolio. Our R&D organization also made great progress. This year, we advanced programs across all three brain health franchises and entered 2020 with five novel NCEE candidates being evaluated across eight indications.

The rest of the approval was also an important step for sage, marking our transition to a commercial company.

This year, we grew our workforce to support our commercial launch and the infrastructure to succeed as a commercial company with an expanding portfolio.

Our R&D organization equally made great progress.

This year, we that's programs across all three greenhill franchises and enter 2020 with five novel anti Kennedy being evaluated over eight indication.

I'll now walk you through the highlights of our fourth quarter and end of year 2019 financial results.

Kimi E. Iguchi: I'll now walk you through the highlights of our fourth quarter and end-of-year 2019 financial results. Revenues were $2 million in the fourth quarter from the sales of Zoresso, and that was compared to $300,000 for the same period of 2018. And that was a result of the collaboration revenues from Shinogi related to reimbursement. We ended the year recognizing 6.9 million Iraqis.

Revenues were 2 million in the fourth quarter from the sales of the wrestle with compared to $300000 for the same period of 2018 and that was a result of the collaboration revenues from shionogi related reimbursement.

We ended the year, recognizing 6.9 million in revenue.

Kimi E. Iguchi: This consists of $4 million of Zoresta sales revenue and $2.9 million in collaborative revenues from Shinobu. We recorded $90.3 million in collaborative revenues from Shinogi for the full year 2018. Selling, general, and administrative expenses were $85.1 million in the fourth quarter. We ended the year with $345.8 million in SG&A expenses compared to $201.4 million for the same period of 2018. Our transition to a commercial company contributed to the increase in SG&A for 2019. The increase was primarily due to personnel-related expenses and corporate infrastructure costs to support expanding operations and the Zorreso Law.

This consists of 4 million of the rest of sales revenue and 2.9 million and collaborative revenues from Sidoti.

We recorded 90.3 million in collaboration revenues from Shionogi for the full year 2018.

Selling general and administrative expenses were 85.1 million in the fourth quarter.

We ended the year with 345.8 million SGN expenses compared to 201.4 million for the same period of 2018.

Our transition to a commercial company contributed to the increase in SNA for 29.

The increase was primarily due to personnel related expenses and corporate infrastructure costs to support expanding operations and there's a wrestle launch.

Research and development expenses were 91.3 million in the fourth quarter consistent with the third quarter of 29 team.

Kimi E. Iguchi: Research and development expenses were $91.3 million in the fourth quarter, consistent with the third quarter of 2019. We ended the year with $368.8 million in R&D expenses compared to $282.1 million for the same period of 2018. The advancement of the Landscape Program, as well as the continued research and development efforts across our clinical and discovery pipelines, contributed to the increase in R&D expenses for 2019. We reported a net loss of $168.7 million for the fourth quarter of 2019 and $680.2 million for the full year of 2019. That was compared to $158.4 million and $372.9 million, respectively, for the comparable periods of 2018. Finally, we continue to maintain a solid financial foundation, ending the year with billions in cash, cash equivalents, restricted cash, and marketable securities. As you've heard me say before, we take a deliberate approach to our investments. Looking at the year ahead, we'll continue to invest thoughtfully to sequence assets we believe will create near, mid, and long-term value for our shareholders. I'll now turn it over to Jeff for closing comments.

We ended the year with 368.8 million in R&D expenses compared to 282.1 million for the same carried at 28 team.

The advancement of the landscape program as well as the continued research and development efforts across our clinical and discovery pipeline contributed to the increase in R&D expenses for 2019.

We reported a net loss of 160.7 million for the fourth quarter 2019, and 680.2 million for the full year 2019 that was compared to 150.4 million and 372.9 million respectively for the comparable periods at 20 team.

Finally, we continue to maintain a solid financial foundation, ending the year with <unk> billion in cash cash equivalents restricted cash and marketable security.

As you've heard me say before we take a deliberate approach to our investment.

Looking at your head will continue invest thoughtfully sequence assets, we believe will create near mid and long term value for our stakeholders.

I'll now turn it over to Jeff for closing comments.

Thanks, Ken me before we begin the culinary I want to remind everyone to contain themselves to one question. Each importantly, I also want to thank the team. This age for their hard work and emphasize that our focus in 2020 will be guided by perseverance disciplined execution and rigorous prioritization to ensure an optimal pace of innovation for.

Jeff Jonas: Thanks, Kimi. Before we begin the Q&A, I want to remind everyone to limit themselves to one question each. Importantly, I also want to thank the teams at SAGE for their hard work and emphasize that our focus in 2020 will be guided by perseverance, disciplined execution, and rigorous prioritization to ensure an optimal pace of innovation for what we believe is the leading novel portfolio of NCEs dedicated to treating brain health disorders. Okay, let's open it up for questions.

What we believe is the leading novel portfolio of NCS dedicated to treating brain health disorders, Okay, Let's open it up for questions.

Thank you.

Operator: Thank you. To ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Corey Kasimov with J.P. Morgan. Your line is now open.

A question you will need to press star one on your telephone to withdraw your question press the pound key please standby, while we gotta candy roster.

Our first question comes from Cory Kasimov with JP Morgan Your line is now open.

Hey, good morning, Thanks for taking my question my questions on Sage 207 or is around alone in this possible strategy.

Corey Kasimov: Hey, good morning. Thanks for taking my question. My question is about SAGE 217 or Zaranolone and this possible strategy of evaluating higher exposure levels to maximize activity. So I guess I'm wondering, how confident are you that going to higher doses could result in better efficacy? And are there preclinical, early dose-ranging experiments you can point to that would support this? Thank you.

Are you waiting higher exposure levels to maximize activity. So I guess I'm wondering how confident are you that going to higher dosing could result in better efficacy and are there preclinical early dose ranging experiments you can point to that would support this thank you.

Jeff Jonas: Hey, good morning, Corey. Thanks, everybody. I'm going to start, and I'll turn it over to Steve.

Hey, good morning, Carter, Thanks, everybody I'm going to start and I'll turn it over to Steve what are the things like when you run. These trials one of the things our team has been really good at is looking at things.

Jeff Jonas: One of the things, like, when you run these trials, one of the things our team has been really good at is looking at things like population PK, exposure levels, and, you know, and also physiologic measures such as beta-EEG. And, you know, some of these data we don't make public, but all I can say is, looking at the adverse event profile and the population PK data, we're very comfortable that there's room for a higher dose for this drug and that there's clearly room to believe that, you know, there'll be potential for a larger effect size. I think one of the takeaways from this, and I've seen this in some speculation, is that this is really Drug Development 101. You do your studies, you know you have broader exposure, you look at the POPPK, and then you can make a determination. And that's what is really probative of what the exposure data looks like versus the effect. We're very comfortable that we have room to go higher, and especially with the adverse event profile, we're very optimistic about it.

Things like population PK exposure to level and also physiologic measures such as Beatty EG and you know some of these data we don't make public but I can I. All I can say is looking at the adverse event profile and the population PK data, we're very comfortable that there's room for higher dose for this drug and that is.

Clearly, we believe that that potential a larger effect size I think one of the takeaways from this and I've seen this some speculation.

Is.

This is this is really drug development sort of one or what you do your studies you know yet broader exposure you look at the pop PK and then you can make a determination and that's what really is prohibitive of what the exposure data looks like versus the effect. We're very comfortable we have room to go higher.

Especially with the adverse event profile, we're very optimistic about.

Thank you.

Tazeen Ahmad: Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is now open.

Next question comes from just the in Ahmad with Bank of America. Your line is now open.

Hey, good morning, guys. Thanks for taking my question.

Steve: Hey, good morning guys. Thanks for taking my question. So, Jeff, I just wanted to probe a little bit about an observation that you made in the Mountain Study, which we have consistently gotten follow-up questions on. What's your view about how to control better in any study that you're doing for compliance? So, is it really about choosing your sites? Is it about certain, you know, principal investigators that are better able to monitor patients? But what checks do you think you need to add into your trial designs in order to make sure that that's not a risk going forward in any continuing or new studies that you do?

So Jeff I, just wanted to probably a little bit about an observation that had made in the mountains study, which we have consistently gotten follow up questions on.

What's your view about how to control better in any study that you're doing for compliance so.

Is it really about choosing our sites is about certain principal investigators that are better able to monitor patients, but what Chuck Thank you need to add into your.

And trial designs in order to make sure that that's not a risk going forward and any continuing or new studies.

Yes actually call. This is Steve the way that we look at this as we look at all the procedures in the study it will happen after whether it's the is positive or whether say hasn't met its primary endpoint and look to see whether there is additional instructions we can give to the investigators.

Steve: Hi, yeah, thanks for the call. This is Steve.

Steve: The way that we look at this is we look at all the procedures in the study, whether it is positive or whether it hasn't been its primary endpoint, and look to see whether there are additional instructions we can give to the investigators and instructions to the patients that would additionally achieve compliance. You know, we know that this is always

Structures for the patients that wouldn't additionally, achieve compliance we we know that this is.

As.

Steve: Part of the rigor related to the studies, but overall, the numbers we've seen are small. We've been talking about that as an element as we understand the outcomes from the 301 study, mainly to point out that we continue to be confident in the activity of the drug, the profile of the drug, and what we've seen in terms of our overall profile. So that's the way we think about it, and as we think about additional ways to tweak the trials, we'll certainly do that, but that's how we think about this data.

Part of the rigor related to the studies.

But overall the numbers we've seen a small we've been talking about that as a as an element.

As we understand the outcomes are the three one study really to point out that we continue to be confidence in the activity of the drugs the profile the drug and that we've seen in terms of our overall profile. So that's the way we think about it.

As we think about additional ways to sort of tweak the trials, we'll certainly do that but that's how we think about this data.

Okay.

Steve: Okay, would you be able to provide any color when you provide your update from your FDA meeting about any changes to protocol that would refer to this specifically?

Would you be able to provide any color on when you provide your update from the or after the meeting about any changes to protocol that would refer to them.

What we'll do it for things that are really germane to the overall sort of contact. The study. We may we made such comments, but those are the kinds of things that will share. After we've worked through our strategy moving forward.

Steve: What we'll do is, you know, for things that are, you know, really germane to the overall sort of conduct of the study, we may, we may make such comments, but those are the kind of things that we'll share after we've worked through our strategy moving forward.

Salveen Jaswal Richter: Okay, thank you. Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is now open. Good morning, thanks for taking my question.

Okay. Thanks.

Thank you Sir our next question comes from SAPIEN right there with Goldman Sachs. Your line is now open.

Good morning, Thanks for taking my questions I'm, so with regard to see.

Jeff Jonas: With regard to the other MDD studies, Shoreline, Rainforest, and Redwood, some of these programs are still suspended in light of changes you may be making. Can you just walk us through whether the reads that were previously announced for this year are still on track for readouts, just given the modifications that may be made?

Yes, sure MDD studies, so shoreline reinforced in Redwood.

Some of these programs are still suspended in light of changes you may be making can you just walk us through whether on the read that were previously announced for this year, what that you're on track well for read outs I am just given the modification need.

Hi, This is Jeff.

Jeff Jonas: Hi, this is Jeff. Some of them, obviously, have been paused; we haven't determined final top-line data yet based on what kind of feedback and our processing of feedback from the agency. I think that 303 is fully enrolled. That one, we may have some data on by the end of the year. Again, this is going to be determined, overall, based on what our pathway is with the agency and what studies they deem to be most valuable.

Some of them, obviously being pause will probably we havent determine final.

Topline data yet based on what kind of feedback, we and our processing a feedback from the agency I think that three or three is fully enrolled.

That one we may have some data by the end of the year again. This is going to determine overall based on what our pathway is with the agency and what studies they deem to be most valuable.

Okay.

Thank you.

Paul Andrew Matteis: Thank you.

Thank you.

Paul Andrew Matteis: Thank you. Our next question comes from Paul Matteis with Stiefel. Your line is now open.

Next question comes from Paul Matteis with Stifel. Your line is now open.

Paul Andrew Matteis: Great Thanks so much for taking my questions.

Great. Thanks, much for taking my questions.

Jeff Jonas: I know it's not the right place to speculate on what the FDA might want, but Jeff, I'm just curious. How do you think if the FDA wants more evidence of acute efficacy for MDD? As someone who's kind of planning going forward and thinking about risk mitigation, how many more shots on goal would you want to feel confident that you're really likely going to get another positive trial? In other words, would you want to start at least two or three more studies? And how does the kind of path forward for PPD play into this and whether or not you'd want to do another PPD study as well? Again, not from the regulatory perspective, but from your perspective as it relates to risk mitigation and maximizing the probability of success. Thanks.

I know I know, it's not the right place to speculate on what the FDA might want but Jeff I'm. Just curious how do you think about if the FDA wants more evidence of acute efficacy for MDD as someone who is kind of planning going forward and thinking about risk mitigation, how many more shots on goal would you want to.

Youre confident that you're really likely going to get another positive trial in other words would you would you want to start at least two or three more studies.

And how does the kind of path forward for PPD play into this and whether or not you want to do another PPD study as well again not from the regulatory perspective, but from your perspective as it relates to risk mitigation of maximizing the probability of success. Thanks.

That was a pretty clever way to get around might try to talk about the FDA. However, let me to say this way I think for those of US who have lived with these data we've looked at the population PK, who will look at the data from the trial yet some of which is trial management. We're very comfortable this is an active agent. It really is and I you know we.

Jeff Jonas: That was a pretty clever way to get around my trying to talk about the FDA. However, let me just say it this way.

Jeff Jonas: I think for those of us who have lived with these data, who've looked at the population PK, who've looked at the data from the trial, you know, again, some of which is trial management, we're very comfortable that this is an active agent. It really is.

Jeff Jonas: And, you know, what we always remind people is that we're developing a new chemical entity, not a repurposed drug. And that pathway can be more challenging. With that being said, we're very comfortable that this is an active agent. There are multiple potential scenarios. I specifically don't want to get into that. I think from a risk mitigation standpoint, what the risk is is only going to be known once we understand what the potential pathways are for the drug. So I really can't speculate beyond that, but I think I'd leave it at that. I'm going to turn this over to Mike for a minute.

Always remind people is that we're developing a new chemical entity not a re purpose drug that that pathway can be more challenging with that being said, we're very comfortable but this is an active agent.

There are multiple potential scenarios I suddenly don't want to get into them I think our risk mitigation standpoint, what the risk is only going to be known once we understand what the potential pathways are for the drug so I really cant speculate beyond that.

But I think I'd leave it at that I'm going to turn this over to Mike permit and probably just one other thing from a portfolio perspective, right. So to one seven clearly we have to think about what your question is risk mitigation. How many studies that will come we're a company that has multiple assets right early stage pipeline, we want to continue to make investments to drive long term value in stage. So we will look at this overall as a portfolio approach.

Mike: And probably just one other thing, from a portfolio perspective, right, so 217, clearly we have to think about what your question is, risk mitigation, how many studies, that will all come, but we're a company that has multiple assets, right, early stage pipeline, we want to continue to make the investments to drive long-term value in SAGE, so we will look at this overall as a portfolio approach, but obviously developing our SAGE 2.1 strategy as well.

But all all the obviously developing our sage two on strategy as well.

Alright, thank you.

Mike: All right. Thank you.

Thank you and next question comes from Andrew side with Jefferies. Your line is now open.

Andrew Sy: Thank you. Our next question comes from Andrew Sy with Jefferies. Your line is now open.

Thanks, and good morning. So just wondering if you can help appointees some precedence in the neurology space, where and after he has allowed a country to amend one of its clinical trials midway such as adding a new dose or changing the enrollment inclusion criteria.

Steve: Thanks, and good morning. I was just wondering if you could help point to some precedents in the neurology space where, you know, the FDA has allowed a company to amend one of its pivotal trials midway, such as adding a new dose or changing their enrollment inclusion criteria. And then, you know, doing so enabled that company to get its drug approved. I just really wanted to get a better understanding of how common this is in the neurology space. Thanks.

Then doing so enable that complaint again its drug approved just really wanted to get a better understanding of how calm and this is in the neurology. Thanks. Thanks.

Yes, the way that we think about it is the following.

Steve: Yeah, the way that we think about it is the following: Yeah, well, first of all, SORESO would be a great example where as we move forward, we took what were originally phase two trials, and we're able to have discussions under breakthrough to agree in what ways we are able to collect data, handle them, and use them for a filing. So there's nothing magic about this.

Well first of all Sorrento would be a great example, where as we move forward. We took what were originally a phase two trials, we're able to discussions under breakthrough to agree and what ways, we able to collect data handle them and use them for a filing so there's nothing magic about this it's really about thinking through what makes sense in order to demonstrate the efficacy.

Steve: It's really about thinking through what makes sense in order to demonstrate the efficacy of the drug and making sure that those are, ultimately, ones that we'd be able to use for a filing. That's the way we think about it. It's one of the reasons why, as Jeff has said, it's premature to speculate about how we might do it. It's really most important to understand what the FDA expects, put that through our own internal discussions on how to get there, and then be able to talk about that more broadly. Yeah, I think the other point is, if we, for example, if we talk about amending, which again was acceptable, obviously, with the SORESO program,

The drug and making sure that those are ultimately at the end of the day ones that we'd be able to use profiling. That's the way we think about it. It's one of the reasons why as Jeff said scripture to speculate about how we might do it it's really most important to understand what the F. you expect but that through our own internal discussions I'd have to get there and then be able to talk about that.

Yeah, I think the other point is if we for example, we talk about amending which again was acceptable obviously with those investment program, where the phase two became a phase three so there you have we clearly a precedent not only in the industry Best company. The other point to remind you is that we are.

Jeff Jonas: The Phase 2 became a Phase 3. So there, you know, we clearly have precedent not only in the industry but as a company. The other point to remind you is that we are, you know, the first data set has already been locked. So the issues of multiplicity really don't pertain.

First data set has already been locked so the issue that multiplicity really don't pertain.

So this is that will be a separate study what we're taking advantage of is that it's really an advantage of operating leverage is that we have sites that are still open. So we don't have to go through the startup and training again and so all we're doing is taken operating leverage will be calling it amendment, but it's going to be an independent trial with an independent SAP. So the so it's you really have to look at it very.

Jeff Jonas: So this will be a separate study. What we're taking advantage of, and it's really an advantage of operating leverage, is that we have sites that are still open. So we don't have to go through the startup and training process again. And so all we're doing is taking operating leverage. We'll be calling for an amendment, but it's gonna be an independent trial with an independent staff. So you really have to look at it very differently. It's not technically; it's an amendment technically, but not in actuality.

Differently not technically it's an amendment in technically but not an actuarial.

Laura Kathryn Chico: Right, that makes sense. Thank you. It was very helpful.

Right that makes sense. Thank you very helpful.

Steve: Thank you. Our next question comes from Laura Chico with Wedbush Securities. Your line is now open.

Thank you. Our next question comes from Laura Chico with Wedbush Securities. Your line is open.

Hi, good morning, and thanks for taking my question I guess, just one on you mentioned in quite a bit on population PK and amendments for 207.

Ritu Subhalaksmi Baral: Good morning and thanks for taking the question. I guess just one on, you were mentioning quite a bit about population PK and amendments for 217. Have you elaborated at all in terms of whether there may be a potential food effect? And I guess the reason I'm asking is, one, how that would impact future amendments, but also secondarily, what does this mean or the implications for prior studies? And I guess specifically I'm thinking about the bipolar study, which used a 30 milligram dose there. So any elaboration on how you're managing food consumption in subjects in the trials? Thanks.

Have you elaborate at all at all in terms of whether they may be a potential food effect I guess the reason I'm asking is one how that would impact future.

Limits, but also secondarily, what does this mean or the implications for the prior studies and I guess, specifically I'm thinking about the bipolar study, which used to 30 milligram dose there so any any elaboration on how you're managing.

Food consumption and subjects in the trials. Thanks.

Yes, so Laura yeah, there's a lot of speculation out there I'll just sort of put address there's a food effect in the drug needs to be administered with food that is pretty straightforward.

Steve: Yeah, so Laura, yeah, there's a lot of speculation out there. I'll just sort of put that to rest.

Steve: There's a food effect, and the drug needs to be administered with food. That's pretty straightforward. You know, as we've talked about before, we look at things like in clinical trials, you know, how to make sure that those instructions are as specific as possible. Getting to the other part of your question, remember that the bipolar study was an open-label initial signal-finding study, and, of course, we used that for internal decision-making to help us understand potential signals. So I would separate those two out. Really, the issue is, you know, how best to instruct patients, assuming that we're getting to a filing, on how best to take the medication to enhance the likelihood of successful patients.

As we've talked about before we look at things like in clinical trials, you know how to how to make sure that those instructions or a specific as possible.

Getting to the other part of your question remember that the bipolar study that was an open label initial signal finding study and of course, we use that for internal decision, making it help us understand potential signals. So I would separate those two out really the issue is.

How best to instruct patients assuming that we were getting to a filing on how best to take the medication to.

Like the this doesn't it.

Thank you.

Next question comes from Ritu Baral with Cowen Your line is now open.

Hey, guys. Thanks for taking the question.

Steve: Thank you. Our next question comes from Ritu Baral on Cowen. Your line is now open.

My questions on I guess more previous.

Traction and your impressions of the current status of guidance not not technically asking about the refund interactions that.

Ritu Subhalaksmi Baral: Hey guys, thanks for taking the question. My question is on, I guess, more previous FDA interaction and your impressions of the current status of guidance. I'm not technically asking about the recent interactions, but suppose Rainforest should not yield the data that we want. Can you talk about your confidence that a relapse prevention study like Redwood would be enough to support MDD? NDA filing by itself in the absence of a potential positive great

Suppose rain forest should not yields the data that we want can you talk about your confidence that relapse prevention study like Redwood would be enough.

To support the.

MDT.

And da falling.

By itself in the absence of.

A potential positive reinforcement.

Steve: Yeah, I mean, I think what you're really asking is what's.

Yes, I mean, I think what you really asking.

Steve: Hello?

As well.

Steve: That's great!

Hello.

Steve: Hello? Yeah. Okay. All right. There we go. All right. So I hope that completes the answer. Yeah.

Yes.

That's great.

Hello.

Hi, good alright, alright.

All right. So I hope that that fleets, the and [laughter] very very clear now about why.

Steve: I hope it's very, very clear now what the answer is.

Yes [laughter].

Steve: Okay. Okay.

[laughter] enrolling at a five seconds away, we'll take the next question.

Steve: We'll take the next question now.

[laughter].

Steve: I'll roll it all the way back. I think what you're asking, Ritu, is really what our path forward for the Landscape Program is and where we might go.

Yeah, I'll I'll roll off.

I think what you're asking me to is really what's our cat food for landscape programming and where we might go well, let you know and of course mirroring the bits of data we've spoken to that point when I can tell you right now as we've always said we've needed data from shoreline as well as from rain forest as part of our overall filing you know, but the really answer.

Steve: And, of course, we're in the midst of that, and we've spoken about it before. But what I can tell you right now is that we've always said we needed data from Shoreline as well as from Rainforest as part of our overall filing.

Steve: But the real answer is the one that Jeff gave right up front, which is when we finalize our discussions with the FDA and sort that through strategically, we'll share what the plan is forward. And, of course, we are continuing to be very confident in the overall profile of the drug. It's an opportunity to get patients well quickly, and that allows us to have some, along with breakthrough discussions, ongoing discussions with the agency about how to bring this medicine to patients most efficiently. It's the way we always think about drug development, and that's what we'll be doing in this case as well.

There is the one that Jeff game right up front, which is you know when we when we finalized our discussions with the FDA and sort that through strategically we'll share with the plan is forward and of course, we're very we are continue to be very confident in the overall profile. The drug it's opportunity to get patients will quickly that allows us to have some along with rates.

Through.

Some discussions ongoing way with the agency about how most efficiently brings medicine to patients. It's the way, we always think about drug developments, but we'll be doing in this case as well.

Got it thanks.

Ritu Subhalaksmi Baral: Got it, thanks.

Thank you.

Akash Tewari: Thank you. Our next question comes from Akash Tewari with Wolf Research. Your line is now open.

Next question comes from a Castellari with Wolfe Research. Your line is now open.

Hey, guys. So given your disclosure today about potentially slower as the rest of the center preparedness and Ah you know, including the higher dose arm potentially ensure line I wanted to ask maybe about your cash burn expectations for the upcoming year and weather pulling back on this all right.

Akash Tewari: Hey guys, given your disclosure today about potentially slower Zolresto center preparedness and including the higher dose arm potentially in Shoreline, I wanted to ask maybe about your cash burn expectations for the upcoming year and whether pulling back on the Zolresto launch just for a moment is a possibility if you're trying to optimize your pathway forward for 217. And how important is your current cash balance in thinking about the development path for 217? Does that come up number one in the discussion, or is the first consideration doing what's right for 217 and cash kind of a secondary consideration?

The launch Jets for a moment is a possibility if you're trying to optimize your pathway forward for 217 and you know how important is your current you know.

<unk> cash balance in in kind of.

Thinking about the development path for 217 is that it does that come up number one and discussion or it's the first consideration doing what's right for you when seven and cashes kind of the second secondary consideration. Thanks.

Mike: Thanks.

Hey, Josh as Mike and I'm going to opt internal but can you, but let me take us all wrestle piece right and I'll turn it came to the more broadly how we're thinking about resource allocations lets you know what your question about resource allocation and how much we're allocating to zilretta lets just step back for a second how we think about you know resourcing as already so maybe you step back and think about first product ever approved impose partner freshen shifts.

Mike: Akash, this is Mike, and I'll then turn it over to Kimi, but let me take the Zoreso piece, and then I'll turn it over to Kimi to discuss more broadly how we're thinking about resource allocation. Your question about resource allocation and how much we're allocating to Zoreso, let's just step back for a second and think about how we think about resourcing Zoreso. Maybe step back and think about the first product ever approved in postpartum depression, shifting the paradigm, hospital-based launch, covering a wide range of OBGYNs and psychs. We sourced this to really build this thing out. We knew it was going to take time. We said all along that it was going to take time to get there. We know the product is having meaningful benefits for moms, and so we continue to focus on driving sites of care and focusing on our strategy so that we can continue to see the guidance that we gave.

The paradigm hospital based launch right covering a wide degree of LPG volumes insights. We resource. This you know it's a really built this thing out he knew what was going to take time, we said all along was going to take time to get there. We know the product is having meaningful benefits to moms and so we continue to focus on driving sites of care and focusing on our strategy that we can continue to see that guidance that week.

A modest growth over the next couple of quarters, we expect an accelerated growth rate in the second half of the year. So we will always look at our resource allocation for the rest will make sure. We're deploying our dollars to the things that we think drive the most value and drive patient access and we will always put that into the corporate context as well about what can be kinda talk or yeah sure. Thanks, Mike and Michael.

Mike: modest growth over the next couple of quarters, but we expect an accelerated growth rate in the second half of the year. So we will always look at our resource allocation for Zoreso and make sure we're deploying our dollars to the things that we think drive the most value and drive patient access. And we will always fit that into the corporate context as well, which I'll let Kimmy talk through.

Mike: Yeah, sure. Thanks, Mike.

Kimi E. Iguchi: And Mike alluded to this earlier, is when we think about how we resource our programs, and it's really about thinking across everything. So thinking across commercial and thinking across R&D. I mean, resource allocation is one of the most important things that we do as a leadership team and throughout the company. So we always think about the near, the mid, the long-term opportunities, and are we balancing that, and are we balancing risk? So those are the kinds of things that we think about as we determine where we should allocate our resources. You also had a question on CASHBURN, and so we haven't been very specific right now on CASHBURN, and a part of that relates to waiting until we understand a path forward for xeranilone, but with regards to, and that's from the R&D perspective, but when you think about SG&A, we did do a good deal of our build last year in 2019 for the launch of Xilresso, and preparing to be ready to really

To this earlier when we think about how we resource.

Our programs and it's really about thinking across everything so thinking across commercial and thinking across R&D. I mean resource allocation is one of the most important things that we do as the leadership team in it and throughout the company. So we always think about the near the mid no long term opportunities and are we balance not in our rebalancing.

So those are the kinds of things that we think about as we determine where we should allocate our resources.

You also had a question on cash burn and so we haven't been very specific right now on cash burn it a part of that relates to your waiting to we understand a path forward for is the analog but with regard to and that's on the R&D perspective, but when you think about S. DNA, we didn't do a good deal of our build last year 20, Nike for the law.

Gotcha, Zilretta, so and preparing to be ready to really.

Kimi E. Iguchi: Can you hear us?

Kimi E. Iguchi: Yeah, I can hear you. Oh, OK. Yeah. So do we.

[laughter] can kill you here, yeah, I can hear okay. Yeah. So we don't expect it S. DNA will continue to grow into next year.

Kimi E. Iguchi: Yeah, so we don't expect that SG&A will continue to grow into next year.

Danielle Brew: Great, thanks so much.

Great. Thanks, so much.

Thank you. Our next question comes from Danielle drill with Piper Sandler Your line is how open.

Jeff Jonas: Thank you. Our next question comes from Danielle Brew with Piper Sandler. Your line is now open.

Danielle Brew: Hi guys. Good morning and thanks for the question. Jeff, I'm just curious about how I should be thinking about the progression from the time the FDA meeting minutes are received to when you'll update the street on next steps. Should I anticipate an update shortly after the minutes, or is there still work that will need to be done internally? Thanks.

Hi, guys. Good morning, and thanks for the question, Jeff I'm just curious.

How I should be thinking about the progression from the time asking a meeting minutes I received to winning I'll update the street and that should I anticipate an update shortly after the minutes or if there's still a work that will need to be done internally. Thank.

Jeff Jonas: Hey Danielle, I think it's a top tier question, which is: it really depends on how the final feedback comes to us. And as you know, sometimes, I know you know, sometimes what you receive is very clear, and you can make... Sorry, sometimes there are, we're having a little technical issue here. Sometimes there are; It's hard to talk through our N95 masks. Sometimes you have commentary that requires clarification in a call. So, as we've said, we anticipate we'll have the meeting in minutes completed in the first quarter. And once we process those and determine what a pathway may be, at that point, we'll be able to communicate.

Hey, Danielle I think that you know it's a it's a top question I talk to your question, which is it really depends on what how the final feedback comes to us and as you know sometimes I know you know sometimes well what you receive is very clear and you can and you can make.

Sorry, sometimes there we're having a little technical issue here, sometimes there are a.

It's hard to talk through our and 95 masks yeah [laughter], sometimes you have commentary that requires clarification in a call. So it. So as we said we anticipate will have the meeting in minutes completed in the first quarter, and what and will and once we process those and determine what a pathway may be at that point.

Well, we'll be able to communicate.

Jeff Jonas: As Jeff said, the meeting will be in the first quarter. We'll get the minutes, and ultimately have internal discussions. The teams themselves are working through potential options based on what we think may ultimately come out of these. And as Jeff said, depending upon the outcomes of those discussions, we'll share those as efficiently as possible. We've always done that, and that's what we intend to do in this case as well.

As soon as Jeff said, the meeting will be in the first quarter, we'll we'll get the minutes.

Ultimately have internal discussions the teams themselves are working through potential options based on what we think may ultimately come through these and as Joe said, depending upon the outcomes of those discussions with we'll we'll share those as efficiently as boss, we've always done that and as we intend to do in this case as well.

Matthew Harrison: Okay. Thank you. Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is now open.

Understood. Thank you.

Thank you.

Our next question comes from Matthew Harrison with Morgan Stanley. Your line is how often.

Matthew Harrison: Hi, thank you. This is Max Skoron from Matthew Harrison.

Hi. Thank you. This is Mac score on from Matthew Harrison quick question, I'm wondering where you expect de risking or proof of concept data for three to four and 718, specifically you clinical evidence that these drugs are active in the disease state beyond biomarker driven data. Thank you very much.

Matthew Harrison: Quick question, when can we expect de-risking or proof-of-concept data for 324 and 718, specifically clinical evidence that these drugs are active in the disease state beyond biomarker-driven data? Thank you very much. Hi Max. This is Jim.

I'm axis is Jim I'm happy to take that question, Yeah, I think the answer for both programs as we are moving forward.

Jim Doherty: I'm happy to take that question. Yeah, I think the answer for both programs is that we are moving forward in both cases. We're making good progress. For 3.2.4, I'll take that first.

In both cases, we're making good progress for three to four I'll take that first that molecules. Our next gap and it's got a profile that's differentiated from the first two but still has the same pharmacology as the first two and so as we move into the neurology space. Our first patient population will be a central summer.

Jim Doherty: That molecule is our next gabapam. It's got a profile that's differentiated from the first two, but it still has the same pharmacology as the first two. As we move into the neurology space, our first patient population will be central tremor. Of course, we already have data, clinical data, on central tremor, with small studies with both Zoreso and then separately with Zoranolone showing acute effects in essential tremor patients. In 2019, we, in a small open-label Phase 1 study, replicated those findings with SAGE 3.2.4. The next step is to move forward into a Phase 2 study, a placebo-controlled double-blind study, replicating those effects with SAGE 3.2.4. I would say we do have some clinical data already with SAGE 3.2.4 in essential tremor. In the case of 718, this is an NMDA positive allosteric modulator, so the front end of our neuropsychiatric franchise and a different mechanism of action than the GABA compounds we've talked about quite a bit in the past.

Of course, we already Oh data clinical data in a simple from or with a small studies.

Resto and then separately was around although I'm showing acute effects in essential tremor patients and in 29 team. We a small open label Phase one study replicated those findings with phase three to four so the next step is to move forward into a phase two study a placebo controlled double blind study of replicating the success.

From a three to four so I'd say, we do have some clinical data already was a speech before into essential tremor.

And the case of seven wanting a this is an enemy Yang pauses about third modulators to the front end of our nurse psychiatric franchise and a different mechanism of action and the GABAA compounds, we talked about quite a bit in the past and I would say there as well although the focus in 29 team was on phase one studies looking at safety and Tolerability pharmacokinetics.

Jim Doherty: I would say there as well, although the focus in 2019 was on Phase 1 studies looking at safety and tolerability, pharmacokinetics, and those sorts of things, we did also include work looking at patient results. In the fourth quarter, we announced results from a small Phase 1 open-label study in Huntington's disorder where we were able to show, similar to what we showed earlier in the year in Healthy Volunteers, acute improvements in executive function in Huntington's disease. That program will move forward in 2020. Instead of moving directly into a placebo-controlled study in Huntington's disease, these results are interesting enough that we really want to get a better sense of what other patient populations could also benefit from this novel mechanism of action. Our next step is to broaden our investigations in small studies looking for the same sorts of cognitive improvements in additional patient populations. Okay, thank you.

That is another thing. We did also include we're looking at South Asian results. So in the fourth quarter, we announced results from a small phase one open label study in Huntingtons disorder, where we're able to show similar to what we showed earlier in the year in healthy volunteers improvements acute improvements and executive.

Uh huh.

So that program will move forward in 2020, instead of moving directly and we see well controlled study in Huntingtons disease. These results are a interesting enough that we really would want to get a better sense of what other patient populations could also benefit from this novel mechanism of action. So our next step is to broaden our investigations it's.

Mall studies looking for the same sorts of Cogs and improvements in additional patient population.

Okay. Thank you.

Jim Doherty: Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is now open.

Thank you.

Next question comes from Brian Abrahams with RBC capital markets. Your line is now open.

Brian Corey Abrahams: Hey guys, thanks so much for taking my question. As we think about the inputs that go into selection of higher 217 doses on the backdrop of the evolving population PK info, I was curious if you could tell us a little bit more about the consistency of drug exposure patient-to-patient that you saw in Mountain, how much higher exposure may have correlated to HAMD response, and then the range of exposures relative to those that you might expect to achieve with, say, a 40 or 50 mg dose Thanks.

Hey, guys. Thanks, so much for taking my question as we think about the inputs that go into selection of higher to one seven doses on the backdrop of the evolving population PK info I was curious if you could tell us a little bit more about the consistency of drug exposure a patient to patient or that you saw in mountain how much higher exposure.

We have correlated to Ham D response, and then the range of exposures relative to those that you might expect to achieve would say a 40 or 50 make dose. Thanks.

Hey, Brian It's Jeff I mean, I'll, just be where even though we haven't disclosed a lot of that those data that's going to be clear what I can tell you, though is what I said earlier is that we believe there is a correlation between exposure and also some certain not physiologic markets as well when we've done it I have a very comfortable with that so and again, if and as you the key to this drug.

Jeff Jonas: Hey Brian, it's Jeff. I mean, I'll just be brief. You know, we haven't disclosed a lot of that data, just to be clear. What I can tell you, though, is what I said earlier: we believe there is a correlation between exposure and also some certain physiologic markers as well when we do it. And again, the key to this drug, and I think you all know why, is looking at the population of PK and understanding that dose-response relationship, dose-exposure relationship, which we think we have established.

Thank you all know is is it for that is like looking at the population PK and understanding that dose response relationship dose exposure relationship, which we think we we have established.

Yes.

Jeff Jonas: Yeah.

Steve: This is Steve. The way that we do it is more than simply looking at correlations between POPQA exposure and dose. One of the advantages now of having a program where we've had more than a couple of thousand patients who have been exposed is we're able to do more advanced modeling of these exposure-response relationships, and that's something that also goes into that decision-making process. So really be able to understand those relationships.

Yeah. This is Steve would wait and whether we do it is is more than simply looking at correlations between a hockey exposure in dose of what are the advantage of dealt with having a program. We've had we've had more than a couple of thousand patients who've been exposed as we're able to do more advanced modeling of a these exposure response.

Its relationships and that's something that also goes into that decision, making process. So you don't really be able to understand those relationships.

Brian Corey Abrahams: Got it. Thanks, Steve, and thanks, Jeff.

Got it thanks, Steven Thanks, Jeff.

Thank you.

Gary Nachman: Thank you. Our next question comes from Gary Nachman with BMO Capital Markets. Your line is now open.

Next question comes from Ghana, two men with BMO capital markets. Your line is now open.

Hi, I'm.

Gary Nachman: Since Shoreline seems like the next big data point for Zoran alone, talk about progress with that study.

Sure line seems like the next big data point for Saran alone talk about progress with that study and what you hope to see from it.

Barry E. Greene: Would it then likely be pushed out to 2021?

What it will inform you about the activity of the drug and if you end up adding another cohort two that study could you still have data in 2020 or would it then likely be pushed out to 2021. Thanks.

Barry E. Greene: SAGE Therapeutics

Barry E. Greene: Thanks for the question. It's an important one.

Yeah. So yeah. Thanks for further question. It's an important one shoreline is an open label study actually looking at the responses in patients who had been risk who responded initially to 207. We then follow on route throughout a year and the goal of this study is to look at how often patients need to be.

Barry E. Greene: Shoreline is an open-label study actually looking at the responses of patients who responded initially to 217 who we then follow throughout a year. The goal of the study is to look at how often patients need to be retreated and what those outcomes are. So really, this is the largest cohort of patients inside of a development trial for depression that's ever been undertaken, and it provides some very fundamental information that we don't have to date for depression broadly and for 217 specifically. So it'll give us a lot of understanding both of how the medicine is used best, what patterns of retreatment we might expect and in whom. And since it's an open-label study, we're able to make If we are to change doses or increase doses and have a new cohort, then, as Jeff said before, those may be handled as an independent group, but we'd still be able to have data on those patients that are fully enrolled as anticipated this year.

Retreated.

And what are those and one of those outcomes. So really this is the largest the largest a cohort of patients inside of a development trial for depression, that's ever been undertaken and provide some very fundamental information that we don't have a today for depression broadly in for two and seven specifically in other words, we'll be able to under.

And what patterns of Retreatment are out there potentially whether there are differences in those patients that are able to be making for very long periods. We've already spoken about the fact that we've seen some patients within these trials being able to me they maintain for for very long periods without additional retreatment. So it'll give us a lot of understanding both of how the.

This is used best what patterns of Retreatment, we might expect and in who and you know since it's an open label study were able to make use of those data in an ongoing away.

If we are to talk if we were to change doses or increase doses revenue cohort than they would as Jeff said before those there's maybe handled as an independent group.

But we still be able to have data lupus patients that are fully enrolled as anticipated this year.

Mike: And one other thing, Gary; this is Mike. To add to that, one of the other important pieces of 303, the Shoreline study, is about pricing strategy. Steve said we're going to get information on how patients are treated and how often. That will ultimately help formulate what our pricing strategy is going to be on a per-dose basis for Zorana1.

One other thing Gary this is Mike to add onto that one of the other important pieces of three or three though the shoreline study is from a pricing strategy as Steve said, we're gonna get information on how patients are treated how often that will ultimately help formulate what our pricing strategy is going to be on a first dose basis for a it's around alone.

Mike: And are there both MDD and PPD patients in that study?

Okay and are there both MDD anti PD patients in that study.

Is it brought enough.

Mike: Is it broad enough? This is a study focused on the MDD program. Just like in Zorreso, long-term data has not been part of the PPD program, so this is an MDD-focused trial.

No. This is a study focused on the MDD program just like in Sorrento.

Long term data has not been part of the the PPD program. So this is MDD focus trial.

Mike: Okay. All right. Thanks.

Okay, all right. Thanks.

Marc Harold Goodman: Thank you. Our next question comes from Marc Goodman with SCB Learning. Your line is now open.

Thank you I'm next question comes from Marc Goodman with STB Liang.

Hi, Linda Sullivan.

Marc Harold Goodman: Hi, thanks for taking my question. This is really on the line for Marc.

Hi, Thanks, Thanks for taking my question. This is really on the line for Mark.

Mike: So I have two quick questions. First, can you talk about patients' and doctors' feedback so far for Zorresso's drug profile and their Zorresso experience in general? And second, can you provide more color on the upcoming essential tremor study for SAGE 324? And what data should we expect from the trial? Thanks.

Two quick question first I talk about patients and doctors feedback so far for del rats those.

Dropped drop out on their directories parents in general and second can you provide more color on upcoming essential tremor study for stage three plenty for and what they're not should we wrap on the trial. Thanks.

Mike: Yeah, this is Mike. I'll take the first part on patient HCP feedback for Xoreso. So as we said, you know, the meaningful benefits that we're seeing in patients mirror what we saw in the clinical studies for Xoreso, right? It's been great to see that in the real world. That's one of the first things you look for when you launch a drug: does the data that you saw in the clinical trials get replicated in the real world?

Yeah. This is Mike I'll take the first part on the patient ATP feedback was already so as we said yeah. The meaningful benefits that were seeing in patients is mirroring what we saw in the clinical studies for the rest already been great to see that in the real World. That's one of the first thing is you look for when you launch of drugs as does the data that you saw in the kind of the trial does it get replicated in the real world and for the patients.

Mike: And for the patients who have been treated, they've seen meaningful benefits, which is really exciting for the team and motivational for the sites of care as well to kind of push through some of the steps to activate. On the HCP side, you know, as you saw, we've increased the number of HCP referrals to over 300 in this quarter. The patient demand for the year was 500, 300 in the third quarter, which is a 50% increase. So we've seen a meaningful increase in both patient demand and HCP referrals. One of the points that's probably important to note, consistent with what we thought going into the launch, HCPs are using this initially in the severe patient population, but as they gain more experience, we think there'll be an opportunity to move this forward in the treatment paradigm for PPD.

I've been treated they'd seen meaningful benefits, which is really exciting for the team and motivation for the sites of care as well, it's kind of pushed through some of the steps to activity on the HCP side, you know that we as you saw we've increased the number of HCP referrals to up over 300, and this quarter the patient demand for the year was 500 300, and the third and what are some 50% increase we've seen meaningful increase.

These and both patients and and any CP referrals one of the point, that's probably important to note consistent with what we thought going into the launch the AC piece are using this initially in the severe patient population, but does the game where experience we think there'll be an opportunity to move this board a in the treatment paradigm for PPD I'll turn it over to Jim on the that's for 24 question are you keep thanks, Mike Yes.

Jim Doherty: Thanks, Mike. Yeah, and so for the Essential Tremor Trial 4.3.2.4, the study will start in the first half of the year, and the study is a Phase II placebo-controlled double-blind study comparing two arms, placebo relative to a 60-milligram dose of SAGE 3.2.4. The primary endpoint is reduction in tremor, upper limb tremor, really the same thing that we did in our open-label study. And the goal of the study is quite simply to, in a placebo-controlled, blinded study, replicate the kinds of reductions in tremor that we saw with the Phase I work. The other difference, of course, being that Phase I work was acute. This is a 30-day dose. Thank you.

And so for the essential tremor trial for three to four Oh. This study will be starting in the first half of here. In this study is a phase two placebo controlled double blind study comparing two arms placebo relative to 60 milligram dose of stage three to four.

Primary endpoint is reduction in tremor upper limb drama or really the same thing that we did in our open label study in the goal other studies quite simply too in a placebo controlled blinded study to replicate the kinds of reductions in tremor that we saw with the phase one work. The other difference of course being phase one work was acute this is a.

Every day doesn't study.

Yeah, I think it's very helpful.

Our next question comes from Tencent and show with Guggenheim. Your line is open.

Jim Doherty: Our next question comes from Yatin Suneja on Guggenheim.

Thank you and thank you for the opportunity to ask a question just a couple could you maybe share your thinking about the path forward in PPD based on current data set what was the thinking for not seeking approval in 29 phenol Robin sex access if long term safety was not the gating factor is that's changing thinking now.

Yatin Suneja: couple. Could you maybe share your thinking about the path forward in PPD based on the current data set? What was the thinking for not seeking approval in 2019 after Robin's success if long-term safety was not the gating factor? Is there a change in thinking now? And then the second question is, if you were to test a higher dose, could you please help us understand the type of safety data you would need to build? Would that change the NDA submission timeline in any way versus a scenario where you don't have to test a higher dose?

The second question is.

If you want to test a higher doors could you. Please help us understand the type of safety data you would need to build could that change the NDS submission timeline in anyway. What it is a scenario where you don't have for desktop.

Jeff Jonas: Thank you.

Thank you.

Jeff Jonas: This is Jeff. I'll be quick.

This is Jeff I'll be quick.

When we announced the breakthrough program. The original pathway was that we needed to shoot depressions in one PBD plus size the safety data for a for an approval for both indications obviously, that's one of that many potential pathways that we're now considering and we'll have some so we can't really comment beyond that since that's.

Jeff Jonas: When we announced the breakthrough program, the original pathway was that we needed two depressions and one PPD, plus safety data, for approval for both indications. Obviously, that's one of the many potential pathways that we're now considering, and we'll have some – so we can't really comment beyond that, since that's something that will be up for discussion or has been up for discussion, or will be up for discussion with the FDA. So that's from that standpoint.

That'll be something that will be up for a discussion or has been up for discussion or will be up for discussion with the FDA. So that's up from that standpoint with respect to dosing. We do have already a lot of several studies with higher dose exposures, So and I think we with the belong with that so we're pretty tough we're very comfortable.

Jeff Jonas: With respect to dosing, we do already have a lot of – several studies with higher dose exposures. So – and I think that, along with that, we're pretty – we're very comfortable that we can go higher. So we don't think that safety around higher doses will be rate-limiting, but again, this is – all of this will depend on our final decision and pathways after – whenever we receive the minutes after our first quarterly meeting. Great. Thank you very much.

We can go higher with the turned to the overall database, we don't believe that safety for a higher dose will be a rate limiting step for us it's important to remember that while some of the stuff is not as close as we move forward with higher doses. All of these data go to we'll go to the agency the F.D.A. and they will have the opportunity to review it Oh, yeah as we have so.

So we don't think that safety around a higher goes it will be rate limiting but again that this is that all of this will depend on our final decision and pathways. After whenever we received a meeting minutes after our first quarter meter.

Great. Thank you very much.

Jay Olson: Thank you. As a reminder, in the interest of time, we ask that you please limit yourself to one question. Our next question comes from Jay Olson on behalf of Oppenheimer. Your line is now open.

Thank you.

As a reminder, and interest this time, we ask that you. Please limit yourself to one question.

Our next question comes from Jay Olson with Oppenheimer. Your line is now open.

Jay Olson: Thank you for taking the question. As you capture learnings from the Zoloreso launch to leverage for future programs, can you talk about any work you've done to evaluate economic outcomes for patients treated with Zoloreso in terms of potential cost savings to the health care system and how important this type of information will be for the uptake of Zoloreso and PPD and eventually for the launch of Zolorenalone and MDD? Thank you.

Thank you were taking a question as you capture learnings from those little rest of the launch to leverage for future programs can you talk about any work you've done to evaluate economic outcomes for patients treated with to rest so in terms of.

Potential cost savings to the health care system and how important this type of information will be for the uptake of Zilretta. So NPD and eventually for the launch of so around alone and MTD.

Thank you, yes, yes, so really important question, we've been working very closely with payers. There were a health outcomes research, we actually do research and publish a quite a bit we have a recent paper we are doing an indirect comparison between the rest so and available care as well as looking at patient reported outcomes that are.

Steve: Yeah, yeah, so a really important question. You know, we've been working very closely with payers through our health economics and outcomes research. We actually do research and publish quite a bit. We have a recent paper doing an indirect comparison between Zoloreso and available care, as well as looking at patient-reported outcomes in our ongoing programs. And what we've seen are very, very dramatic differences between both Zoloreso and Zolorenalone, as well as standard of care based on these indirect comparisons, both in terms of the number needed to treat, as well as overall aspects of health-related quality of life. So we really do, we are really starting to understand what the specific areas that payers are interested in around postpartum depression are. Thank you everyone for taking the time back with children and so forth, and for the ability to fulfill appropriate roles as well as what's important for patients with depression itself.

Our in our ongoing programs and what we've seen are very very dramatic differences between both little ressa ones around alone as long as standard of care based on these in direct comparisons both in terms of never needed to treat as well as overall aspects of health related quality of life.

So we really do we are really starting to understand what are they specific areas that payers are interested in rail or in around postpartum depression.

Meaning time back with children, and so forth and the ability to to fulfill oh appropriate rove.

As well as what is what's important for patients with depression itself, just as Jeff I tried to point out we've actually published some of these analyses I recently in CNS drugs and yeah got it was basically a cooper at all and it wasn't CNS drugs I can give we can give you. The reference later, which is a very nice met analysis looking an indirect comparisons between at Rex.

Jeff Jonas: This is Jeff. I just want to point out we've actually published some of these analyses recently in CNS Drugs and

Jeff Jonas: Go out.

Jeff Jonas: It was basically Cooper et al., and it was in CNS drugs, and we can give you the reference later, which is a very nice meta-analysis looking at indirect comparisons between Brexanolone injection versus SSRIs. And that can actually give you some of the data analyses, some of which we've actually now met as we've pioneered. So I think that's well worth taking a look at because that will give you a full picture of what we think about it.

Hello, and a jet and injection versus SS arise and that would that can actually give you. Some of the data analyses some of which we've actually now matters. We pioneered so I think thats, where well we're taking a look at because that will give you a full full picture of how we think about it yeah. Jay This is Mike just to take it one step back. Your question was also on the learnings right from so rest so two to one seven.

Mike: Yeah, and Jay, this is Mike. Just to take it one step back, your question was also going to learnings, right, from XoRESO to 217. And if you think back, the learnings actually go pre-launch, right? What we learned about engaging the payers early on was helping them understand what the unmet need was in PPDM, what the burden of the disease was, some of the things that Steve was describing. So to get the favorable coverage that we have now, the 80% favorable coverage that we have, was the work that we did to educate the payers early on, which will continue with Soranilone, right, at the appropriate time. But we want to continue to feed XoRESO with real-world evidence both on the clinical side and the health-economic side. I think the better value story we can tell, I think the more you're going to see sites lean into it, because they're seeing the efficacy benefits, and they want to see some of the health-economic benefits as well.

And if you think back the learnings each actually go prelaunch right, what we learned about engaging the payers early on was helping them understand whats the young it wasn't PPD and what the burden of disease was some of the things that Steve was describing so to get the favorable coverage that we have now the 80% April coverage that we have was the work that we did to educate payers early on which was the continuation of which will do with Saran alone right at the appropriate time.

Well, we want to continue to feel wrestle with real world evidence both on the clinical side and the health Economics, I think the better value story, we can tell I think the more you going to see sites lean into because they're seeing the efficacy benefits they want.

Some of the health economic benefits as well.

Mike: Super helpful, thank you.

Super helpful. Thank you.

Thank you and next question comes from a massive on with Mizuho. Your line is open.

Vamila Devan: Thank you. Our next question comes from Vamila Devan with Mizuho. Your line is now open.

Mike: Thanks so much for taking the question. Maybe just following up on the Zorreso commentary there, I appreciate the payor coverage comments you've made. My question is just around sort of the total out-of-pocket costs that patients have for a product like this. I know it's early in the year.

Great. Thanks, so much for taking the questions. So maybe just following up on those as Russ. So a commentary there I appreciate the payer coverage comments you've made my question is just around sort of total out of pocket cost the patients have for a product like this I know it's early in this probably not a lot of data yet, but beyond the drug I'm thinking about sort of facilities.

Mike: Provider fees, you know, being in the center for 60 hours. So do you have a sense in terms of what the range is that patients are being asked to pay out of pocket for the totals?

Fusion piece on the fusion or provider fees shipping in the center for 60 hours. So do you have a sensation in terms of whats the range that patients are being asked to pay out of pocket for a total sort of procedure.

Mike: Procedure.

Mike: Yeah, so we're not giving a range in terms of the dollar amounts, but what I can tell you is that SAGE Central plays a critical role, right? We have SAGE Central, and we have financial assistance programs that are set up and designed not only to cover the cost of the co-pays and out-of-pockets for the drug, but also where we can and compliantly do it on the infusion costs as well. So what I can say at this point is that out-of-pocket expenses for patients have not been a barrier, right, in terms of their access to treatment. We'll continue to monitor our financial assistance programs, but it has been a big part of our value proposition to the patients, to the healthcare providers, that if there is financial assistance and we can provide it, we will step in to support the patient.

Yes, we're not giving a range in terms of dollar amounts are what I can tell you is that would say central plays a critical role right. We have stayed central we have financial assistance programs that are set up in design not only to cover the cost the co pays and out of pocket for the drug, but also where we can and completely do it on the infusion costs as well so what I can say at this point is the out of pocket expenses for the patients.

I have not been a barrier right in terms of their access to the treatment and we'll continue to monitor our financial assistance programs, but it's been a big part of our value proposition to the patients to the health care providers that if there is financial assistance and we can provide if you will step in to support the patient.

Thank you. Our next question comes from Tim Lugo with William Blair. Your line is how often.

Hi, This is lock on for Tim. Thanks for taking my questions. I was just wondering if you continue to interrogate the data from the mountains study have you seen any differences between patients that were on a background therapy. This is not already although your baseline measures like anxiety your current somehow.

Timothy Francis Lugo: Thank you. Our next question comes from Tim Lugo with William Blair. Your line is now open.

Timothy Francis Lugo: Hey, this is Lachlan answering for Tim. Thanks for taking the questions. I was just wondering, as you continue to interrogate the data from the Mountain Study, have you seen any differences between patients that were on background therapy versus not or any other baseline measures like anxiety or insomnia?

Yeah, well well the details are available for public disclosure at this point, we are continuing to look at the data to understand whether there's any differentiation within patients the ones that we've talked about are the ones that we've been focusing on maintaining or the the appropriate make sure the patient.

Steve: Well, the details aren't available for public disclosure at this point, but we are continuing to look at the data to understand whether there's any differentiation within patients. The ones that we've talked about are the ones that we've been focusing on, you know, maintaining.

Their compliance it had the appropriate inclusion criteria, but there was nothing that's about the data that would give us pause to date of course, we continue to yard interrogate that internally and that's what that's what we do until you know until we were approved.

Steve: The

Steve: Thank you. Our next question comes from Sumant Kulkarni with Canaccord. Your line is now open.

Thank you.

Next question comes from Sumant Kulkarni, It with Canaccord. Your line is now open.

Sumant Satchidanand Kulkarni: Good morning. Thanks for taking my question. So given all the current evaluation with the 217 program and the ongoing interactions with the FDA, at a very high fundamental level, how has your thought process evolved to maybe suggest that TPD could actually be a very different underlying disease versus MDD, which by its nature is a much more heterogeneous indication without a specific trigger, such as the birth of a baby? Or is this simply a matter of PKPD or dosing differences between these indications?

Good morning, Thanks for taking my question. So given all the current devaluation were the 217 program and the ongoing interactions with the FDA at a very high fundamental level. How has your thought process involved to maybe suggest that BBD could actually be a very different underlying disease wishes MDD, which by its nature has a much more heterogeneous indication without a specific trigger such as a bunch of a baby or this simply.

Mitral PK PD or dozing defenses within these indications.

Joe: This is Joe. I think, you know, it's a good question. You know, I think if you look at how we look at psychiatric disorders, and that has to do with validators of disease states, people with postpartum obviously have a different precipitant. But if you look at their family histories, if you look at the course of the illness, you look at cross-sectional symptomatology, they're very similar to MDD. The major difference, of course, is that PPD, when it resolves, and as it has with so many of our Zolaresto patients...

Hi, This is John I think yeah. This is a good question Yeah. I think if you look at what how we look at psychiatric disorders and that has to do with Validators of disease States people with post part I mean, obviously have a different precipitated but if you look at their family history is if you look at the course of the illness, you look at symptom comp cross sectional Sir.

The mythology, they're very similar with M.D. The major difference of course that PBD, yet when it resolves and as it has with direct with somebody or ours, all resto patient yeah. If a recurrent occurs in a year and there is no childbirth, it's simply categorized as M.D., but if you look at all the other typical validators response to antidepressants whatever they.

Joe: Yeah.

Joe: If a recurrence occurs in a year and there is no childbirth, it's simply categorized as MDD. But if you look at all the other typical validators' response to antidepressants, whatever they may be, family history, things of that nature, they're probably part of the same affective spectrum. Whether women have a different underlying diathesis that makes them more vulnerable, I think that's something that none of us know yet.

May be a family history things of that nature, they're probably part of the same aspect of spectra wet weather women have a different underlying died dialysis that makes them more vulnerable I think thats something that none of us know yet.

Thanks.

Thank you I'm not showing any further questions at this time I would now like to send the call back over to Dr. Jeffs, John F. for closing remarks.

Joe: Thank you. I am not showing any further questions at this time. I would now like to turn the call back over to Dr. Jeff Jonas for closing remarks.

Well, firstly, thanks, everyone and before I and I want to thank the teams that stage for their hard work and you know for us its Asia, we feel like we're creating value with a marketed product in an area of unmet medical need a phase three asset now with a large market indications.

Jeff Jonas: Well, firstly, thanks, everyone. And before I end, I want to thank the teams at SAGE for their hard work. And, you know, for us at SAGE, we feel like we're creating value with a marketed product in an area of unmet medical need, a phase three asset now with large market indications, you know, with two positive pivotal trials, which is a novel agent, a deep pipeline, and a really strong research engine. And not to mention, I think we're in a great financial position with about a billion dollars of cash to exit. With all that said, we have a broad portfolio, many of which we think represent deep opportunities, so our focus in 2020 is going to be guided by our perseverance, really disciplined execution, and rigorous prioritization to really ensure an optimal pace of innovation for what we believe is a leading novel portfolio of NCEs dedicated to treating brain health So with that, I want to thank everyone for their attention today, and have a great day.

You know a two positive pivotal trials, which is a novel agent a deep pipeline and it really strong research engine and not dimension I think we're in a great financial position with about a billion dollars of cash to execute.

With all that said, we're looking at some we have a broad portfolio, many of which which we think represent deep opportunity. So our focus in 2020, it's going to be guided by our perseverance really disciplined execution and rigorous privatization to really ensure an optimal pace of innovation for what we believe is a leading novel portfolio advance ease dedicated to try.

Adding brain health, so with that I want to thank everyone for their attention today and have a great day.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.

Good.

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Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

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