Q1 2022 SAGE Therapeutics Inc Earnings Call

Good morning, welcome to Sage Therapeutics first quarter 2022 financial results Conference call. Currently all participants are in a listen only mode.

Operator: Good morning. Welcome to Sage Therapeutics' first quarter 2022 financial results conference call. Currently, all participants are in a listen-only mode.

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Well it is a property of Sage therapeutics and recordings reproduction or transmission of this call without the expressed written consent of stage therapeutics is strictly prohibited. Please note that this call is being recorded.

I'd like to introduce Helena Rubinstein Investor Relations.

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Good morning, and thank you for joining Sage Therapeutics first quarter 2022 financial results conference call before we begin I encourage everyone to go to the investors and media section of our website at <unk> Dot Com, where you can find the.

Helen Rubenstein: Call is being webcast live on The Investor, website at sageRT.org, is the property of Sage Therapeutics and Recording Production, or transmission of this call without the express is Strictly, Please note that this call is being recorded. And now I'd like to introduce Helen Rubenstein, investor, Good morning, and thank you for joining Sage Therapeutics first quarter 2022 financial results conference call. Before we begin, I encourage everyone to go to the investors and media section of our website at SageRx.com, where you can find the press release related to today's call, as well as the slides that contain supplemental details.

Helen Rubenstein: I'd like to point out that we will be making forward looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

Press release related to today's call as well as the slides that contains supplemental detail.

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

Our subject to certain risks and uncertainties and our actual results may differ materially. Please consult the risk factors discussed in today's press release and in our SEC filings for additional detail. We will begin the call with prepared remarks by Barry Greene, Our Chief Executive Officer, who will provide an overview of the progress during the first quarter. We will also be joined by Jim <unk>.

Helen Rubenstein: Please consult the risk factors discussed in today's press release and in our SEC filings for additional detail. We will begin the call with prepared remarks by Barry Greene, our Chief Executive Officer, who will provide an overview of the progress during the first quarter. We will also be joined by Jim Daugherty, our Chief Development Officer, who will review recent progress in development activities across our programs, and Timmy Eguchi, our Chief Financial Officer, who will review the financial results in the quarter. We will be joined for Q&A by Chris Benecchi, our Chief Commercial Officer. With that, I'll now turn the call over to Barry.

<unk>, our Chief Development Officer, who will review recent progress and development activity across our programs and can we at Gucci, Our Chief Financial Officer, who will review the financial results in the quarter, we will be joined for Q&A by Chris <unk>, Our Chief commercial officer.

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

Barry Greene: Thanks, Helen, and thank you, everyone, for joining us. For Sage, 2022 is off to a strong start. We've laid the groundwork for a year of execution as we make progress on our goals to become the leader in brain health and a top tier biopharmaceutical company. Our efforts come at a pivotal time as we are amid an ongoing brain health pandemic. Triggering Substantial Societal and Lifestyle Disruptions Across Communities.

Thanks Alan.

And thank you everyone for joining us this morning.

Sage 2022 is off to a strong start.

The groundwork for Europe execution as you make progress on our goals to become a leader in brain health and a top tier biopharmaceutical company.

Our efforts come at a pivotal time.

We are amid an ongoing greenhill pandemic.

Triggering substantial societal and lifestyle disruptions across communities.

Barry Greene: The severity and prevalence of symptoms facing our nation require all of us to be prepared. Strengthen Our, As we mark Mental Health Awareness Month, which has been observed in the United States since May 1949. We recommit ourselves to our mission of pioneering solutions to deliver life-changing brain health medicine. Mental Health Awareness Month provides an important reminder of the great unmet need in this area.

Severity and prevalence of symptoms basically our nation require all of us to strengthen our response.

As we Mark mental health awareness month, which had been observed in the United States since may.

<unk> 1949, we recommit ourselves to our mission of pioneering solutions to deliver life changing greenhill.

Mental health awareness month provides an important reminder of the great unmet need in this area.

Barry Greene: It's never been more important to prioritize mental health as an essential component to overall health and well-being. I want to take a moment to underscore the need for novel therapies for people living with MDD and PPP. Disorders where advancement has lagged other critical diseases, with little innovation in the last 60 years. Profile of treatments remains unchanged despite 35 approved treatments in the last 30 years.

It's never been more important to prioritize mental health is an essential component to overall health and wellbeing.

I wanted to take a moment to underscore the need for novel therapies for people living with MTB in PPD.

Orders were advanced and has lagged other critical disease areas.

With little innovation in the last 60 years.

Profile of treatments remains unchanged, despite 35 of the treatment.

30 years.

Barry Greene: Current treatments in the dominant model of mental health care do not address the complex challenges of depression, and they're simply not scalable. Not all patients with depression achieve an adequate response to treatment, and many continue to live with symptoms of their condition, resulting in continued functional impairment. Further, current antidepressants that often take 16 years, if ever, for patients to experience benefits from treatment. Power ability is also frequently an issue.

Current treatments and the dominant model mental health care do not address the complex challenges of depression, and they're simply not scalable.

Not all patients with depression achieve an adequate response to treatment.

And many continue to live with symptoms of the condition, resulting in continued functional impairment.

Further current antidepressants it often takes 60.

Yes, Edwin for patients to experience benefits from treatment.

Tolerability is also frequently an issue.

Barry Greene: Current antidepressants often cause stigmatizing side effects like sexual dysfunction and weight gain, which can be associated with patient non-adherence. The prevalence and impact of depression continued to increase, with an estimated three to four-fold increase in people experiencing symptoms of depression since the start of the COVID-19 pandemic. And it's well documented in the literature and in studies like STAR-D that those MDD patients with elevated anxiety as one of the symptoms of their depression are among the least well served.

Current antidepressants, all can cause stigmatising side effects like sexual dysfunction weight gain which can be associated with patient non adherence.

Further.

The prevalence and impact of depression continued to increase.

An estimated three to four fold decrease in people experiencing symptoms of depression since the start of the COVID-19 pandemic.

And it's well documented in the literature and studies like Star D that those MVD patients with elevated anxiety is one of the symptoms of their depression are among the least well served and.

Barry Greene: In addition, an estimated 1 in 8 mothers in the United States report experiencing symptoms of PPD each year. That's approximately 500,000 women. PPD remains the leading complication of childbirth, and is associated with considerable maternal mortality and morbidity, which continues to rise driven largely by increases among women of color. The current treatment approach in depression is often trial and error. Simply put, people with MDD and PPD deserve better treatment. They deserve a chance to thrive.

In addition, an estimated one in eight mothers in the United States report experiencing symptoms of PPD each year.

Approximately 500000 women.

PPD remains the leading complication of childbirth.

And is associated with considerable maternal mortality and morbidity.

Continues to rise driven largely by increases among women of color.

The current treatment approach in depression is often trial and error simply put people with MTBE in PPD deserve better treatment.

Deserve a chance to thrive.

Barry Greene: That's why we believe there's a significant opportunity to advance the standard of care for treating MBD and PPD with Drialone, if approved. To this end, yesterday, we and our collaborator, Biogen, announced a very exciting step towards bringing Xeranol into market. We began a rolling NDA submission to the FDA for zaranolone to treat MDD. And we remain on track with our plan to complete the submission in the second half of this year, will provide the next update when we complete the submission.

That's why we believe there's a significant opportunity to advance the standard of care for treating mbd in PPD was around alone if approved.

To this end yesterday, we and our collaborator Biogen announced a very exciting step towards bringing <unk> to market. We began our rolling NDA submission to the FDA for <unk> alone treat mbd and we remain on track with our plan to complete the submission in the second half of this year.

We will provide the next update when we complete the submission.

Barry Greene: In addition, we anticipate making an associated NDA filing for Zaranulon and PPD in early 2023, pending results from our scholarship, which we continue to expect mid-2022. Jim will provide more details regarding the SCARLET study and our overall NDA submission, We believe that the totality of the data that we plan to submit to the FDA from data generated in multiple studies evaluating ziranolone and PPD and MBD patients, supports the potential of Zuralum to make a difference for patients.

In addition, we anticipate making an associated NDA filing for <unk> in PPD and early 2023 pending results from our scholar study, which we continue to expect mid 2022.

Jim will provide more details regarding the Scarlet study on our overall NDA submission plans.

We believe that the totality of the data that we plan to submit to the FDA from data generated in multiple studies evaluating <unk> alone PPD and MTBE patients supports the potential <unk> to make a difference for patients.

Barry Greene: We've seen rapid and sustained improvement of depressive symptoms with a well-tolerated safety profile across six positive studies. Based on these data, we believe Zoranolone has the potential to fill the unmet need and serve both people with MDD and PPD and advance the standard of care. Such advancement will require partnership and engagement with all stakeholders, patients, healthcare professionals, payers, patient advocate groups, and policy. And to that end, Sage is already collaborating with these stakeholders to gain the insights we need to effectively prepare our go-to-market approach for Xeraniline to help those living with MDD and PTSD.

We've seen rapid and sustained improvement of depressive symptoms with a well tolerated safety profile across six positive studies.

Based on these data we believes around alone has the potential to fulfill the unmet need and serve both people with davita in PPD and advance the standard of care.

Such investment will require partnership engagement with all stakeholders patients health care professionals payers patient advocacy groups and policymakers.

To that end stages already collaborating with these stakeholders to gain the insights we need to effectively prepare our go to market approach for <unk> to help those living with <unk>.

Barry Greene: Our goal, which the Roundtable has approved, will be to execute a fit-for-purpose launch that prioritizes deep stakeholder insight driven by data, analytics, and monitoring that we believe will enable us to strategically deploy our resources, across all channels at the right time.

Our goal is the rental is approved we'll be the <unk>.

<unk> a fit for purpose launch.

Prioritizes deep stakeholder insight driven by data analytics and monitoring that we believe will enable us to strategically deploy our resources across all channels at the right scale.

Barry Greene: These targeted engagements are needed to enact the change necessary for MDD and PPD patients to get the care they deserve and for appropriate patients with MDD and PPD to receive Xeronal, from our stakeholder interaction. We know that there are many types of people with MBD could potentially benefit from a treatment like Seranto. They include treatment-naive young adults, such as college students, who have an acute stressor that triggers depressive symptoms that derail their lives.

<unk> targeting agents are needed to change necessary for <unk> and PPD patients get the care they deserve.

For appropriate patients within <unk> to receive <unk> alone.

From a stakeholder interactions.

But there are many types of people with MVD can potentially benefit from a treatment like sorrento.

They include treatment naive young adults such as college students, who have an acute stressor that triggers depressive symptoms that derail their lives.

Barry Greene: People are receiving antidepressant treatment, but still suffering. Those with breakthrough symptoms when acute trigger, such as a death in the family, amplifies MDD symptoms despite current treatment. Adherence Challenge Individuals, and importantly, older adults where chronic polypharmacy is a challenge and adding another chronic treatment that would not. As we think about those we could potentially treat, it's important to highlight the unmet need among patients diagnosed with MDD who present with elevated anxiety as a symptom of their depression. Current literature suggests that nearly 55% of people with MDD experience elevated anxiety as part of their depressive state.

People are receiving antidepressant treatment, but still suffering.

Those with breakthrough symptoms when acute trigger such as a death in the family amplified mbd symptom despite current treatment.

<unk> challenged individuals.

And importantly, older adults, where chronic polypharmacy is the challenge and adding another chronic treatment.

Justifies.

As we think about those we could potentially treat it is important to highlight the unmet need among patients diagnosed with MTB present with elevated anxiety is a symptom of their depression.

Current literature suggests that nearly 55% of people with mbd experienced elevated enzyme.

Part of their depressive symptoms.

Barry Greene: And when treated with antidepressants, this patient group experiences poor depression treatment outcomes and lower remission. We've learned that from a clinician's perspective... These patients are incredibly challenging to treat. Current antidepressants are inadequate at resolving the totality of lifelong symptoms these patients experience, and they may increase associated challenges like anxiety and sleep deprivation. However, Zoranolone's mechanism of action is distinct from current antidepressants.

And when treated with antidepressants this patient group experienced poorer depression treatment outcomes lower readmission rates.

We've learned that from our clinicians perspective. These patients are incredibly challenging to treat as current antidepressants are inadequate resolve in the totality of lifelong symptoms. These patients experience and they may increase associated challenges like anxiety and sleep deprivation.

However, <unk> mechanism of action as distinct from current antidepressants.

Barry Greene: Based upon data seen in our MDD study to date, which have included both patients with elevated anxiety as a symptom of their depression, and those without symptoms of anxiety, including data on improvements in quality of life. We believe Xeran alone may be well-suited to address a clear unmet need for people with MBD regardless of their baseline anxiety. It's also important to note that for women struggling with PPD, many present with anxiety as an important feature of their disease.

Based upon data sooner mbd studied to date, which have included both patients with elevated xiety simply move their depression and those without symptoms of anxiety.

Adding data on improvements in quality of life, we believe is around alone.

May be well suited to address a clear unmet need for people with mbd, regardless of their baseline anxiety symptoms.

It's also important to note that for women's training with PPD. Many present with anxiety is an important feature of their disease.

I am confident in the profile, we've seen was around in clinical studies to date, including the data we've generated showing improvement in both core depression symptoms as well as the anxiety symptoms in patients with <unk> and PPD and the differentiated tolerability profile to date and look forward to sharing more on this program throughout the rest of the year.

Barry Greene: I'm confident in the profile we've seen with Zoranil in clinical studies to date, including the data we've generated showing improvement in both core depression symptoms, as well as anxiety symptoms in patients with MDD and PPD, with a differentiated tolerability profile to date, and look forward to sharing more on this program throughout the rest of the year. Now, beyond Zoratelum, we continue to make sustained progress across both our Neuropsych franchise, led by SAGE 718, a wholly owned, first-in-class NMDA receptor PAM, being developed as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction, and our Neuro franchise, led by SAGE 324, which is being evaluated with our collaborator Biogen. Potential Treatment for Patient Suffering, from Essential Tremor and Other Neurological Disorders.

Now beyond <unk>, we continue to make sustained progress across both our neuro psych franchise led by Sage 718, our wholly owned first in class NMDA receptor Pam being developed as a potential oral therapy for cognitive disorders associated with NBA receptor function and our neuro franchise led by phase III.

Barry Greene: Across both franchises, we have six ongoing and planned phase two studies. In the neuropsych franchise with stage 718, these include dimension and surveyor, both for patients with Huntington's disease cognitive impairment. Precedent for Patients with Parkinson's Mild Cognitive Impairment, and a Phase 2 in Patients with Mild Cognitive Impairment and Mild Dementia Due to Ulcerative Colitis.

Two four which is being evaluated with our collaborator biogen as a potential treatment for patients suffering from a central tremor and other neurological disorders.

Across both franchises, we have six ongoing and planned phase II studies in the neuroscience franchise, which states are in 18.

These include dimension and surveyor, both for patients with Huntington's disease cognitive impairment.

Precedent for patients with Parkinson's mild cognitive impairment and a phase II in patients with mild cognitive impairment and mild dementia due to Alzheimer's disease.

Barry Greene: In the neurology franchise, these include PANIC-2 and a long-term open-label safety study, both studying patients with essential tremor. Each of these studies has been intentionally designed to inform paths forward for both SAGE 718 and SAGE 324 that focus on outcomes which are most important to patients. We look forward to providing updates on these studies as they become available. I'm also really excited to welcome Dr. Mark Paul to SAGE as Senior Vice President, Medical Therapy. Mark brings significant experience in scientific research and medical practice across industry and academia to organizations. In his role at SAGE, he will lead our global medical affairs efforts across our program.

And the neurology franchise.

Two long term open label safety study, both studying patients with essential tremor.

Each of these studies has been intentionally designed to inform paths forward for both Sage 718 in phase III for the focus on outcomes, which are most important to patients.

We look forward to providing updates on these studies as they become available.

I'm also really excited to welcome Dr. Mark path to Sage Senior Vice President Medical Affairs.

Mark brings significant experience in scientific research and medical practice across the industry and academia to organization.

In his role at stage he will lead our global medical affairs efforts across our programs.

Barry Greene: Scientific Exchange, KLO Insights, Publications, Presentations at Scientific Congresses, and Plans for Phase 3b-4 Studies are critical aspects of our medical care strategy. I'm confident that Mark's contributions across AIDS will help to further support our relationships with the medical community and patient advocates in support of our goal to become the leader in brain health. And reflecting on our progress during the first quarter in recent weeks, I'm proud of the effort and commitment across our organization, as we continue on our mission of pioneering solutions to deliver life-changing brain health.

Scientific exchange scale insights publications presentations at scientific Congresses, and plans for phase III <unk> studies are critical aspects of our medical care strategy.

Im confident that marks contributions across age up to further support our relationships with the medical community and patient advocates in support of our goal to become a leader in brain health.

And reflecting on our progress during the first quarter in recent weeks I am proud of the effort and commitment across our organization as.

As we continue on our mission of pioneering solutions to deliver life changing marine helping us.

I want to extend my thanks to the entire sales team for their hard work and dedication on behalf of patients and their families.

Barry Greene: I want to extend my thanks to the entire SAGE team for their hard work and dedication on behalf of patients and their families. Looking ahead to the remainder of this year, I believe it's truly an exciting time at Sage as we endeavor to bring long-term value to patients, our employees, and key stakeholders alike. With that, I'd like to turn the call over to Jim for a more detailed discussion of our portfolio progress and current clinical experience. Jim?

Looking ahead to the remainder of this year I believe it's truly an exciting time at sage as we endeavor to bring long term value to patients our employees and key stakeholders alike.

With that I'd like to turn the call over to Jim for a more detailed discussion of our portfolio progress and current clinical experience Jim.

Jim Daugherty: Thanks, Barry, and good morning, everyone. In the first quarter of 2022, we made important progress across each of our three brain health franchises. Beginning with our depression franchise, we're pleased to have initiated the rolling NDA submission in MDD for this program. As a reminder, we're developing Zoranilone in collaboration with Biogen. With the coral study data shared earlier this year, we now have six positive clinical trials with seranilone in MDD and PPD across the Landscape and Nest programs, and the Shianogi Phase II trial in MDD.

Thanks, Barry and good morning, everyone in.

In the first quarter of 2022, we made important progress across each of our three brain health franchises.

Beginning with our depression franchise, we're pleased to have initiated the rolling NDA submission and MTV for this program. As a reminder, we are developing is around alone and in collaboration with Biogen.

With the Coral study data shared earlier this year, we now have six positive clinical trials was around alone and mbd in PPD across the landscape of NES programs and the <unk> phase III trial in MTBE.

The clinical profile, we have seen to date includes one a rapid and sustained reduction in depressive symptoms.

Jim Daugherty: The clinical profile we have seen to date includes, One, a rapid and sustained reduction in depressive symptoms, to a well-tolerated safety profile. Three improvements in quality of life and overall health across domains of healing, functioning, and well-being that were reported by patients and continued post-treatment in the studies where we collected these data. Four, a short treatment course with potential to be taken as needed and a novel mechanism of action.

Two a well tolerated safety profile.

Three improvements in quality of life and overall health across domains of healing functioning and wellbeing that were reported by patients and continued post treatment and the studies, where we collected these data.

For a short treatment course with potential to be taken as needed and a novel mechanism of action and five the potential for a flexible treatment approach in MPD and BBB that may provide optionality to health care providers and patients gives around loan is approved.

Jim Daugherty: And five, the potential for a flexible treatment approach in MDD and PPD that may provide optionality to healthcare providers and patients if Zoran alone is approved. Turning to PPD, we are on track to report top-line data from the Skylark study in mid-2022. And pending completion and results of the Skylark study, we plan to submit an associated NDA submission for Zoraniline in PPD in early 2023. The Skylark study forms an important component for our planned NDA filing package for zaranulone and PPD.

Turning to PPD, we are on track to report topline data from the Skylark study in mid 2022.

And pending completion and results of the Skylark study, we plan to submit an associated NDA submission for <unk> and PPD in early 2023.

It's kind of like studies forms an important component for our planned NDA filing package for us around alone in PPD.

Jim Daugherty: The design of the Skylark study is similar to the Robin study, where we saw positive results in moms with PPD. As a reminder, the Robbins study was a phase 3 study evaluating the effects of Zaranlone 30 mg on depressive symptoms in approximately 151 adult women diagnosed with PPD. In the Robbins study, we saw a statistically significant reduction in depressive symptoms in the Zoranlin R compared to placebo at day 15, the primary endpoint, as well as day 3, day 8, day 21, and day 45.

Designing the Skylark study is similar to the Robin study, where we saw positive results in moms with PPD.

Jim Daugherty: Additionally, Zorana Lung was well-tolerated in the study with a safety profile consistent with what we've seen across the totality of the program. The Skylark study incorporates the learnings from the Robbins study and was developed as a placebo-controlled phase 3 clinical trial evaluating a two-week course of Zaranulone in women with PPD with an additional short-term follow-up. Notably, the Skylark study differs from the Robin study in three key areas.

As a reminder, the Robin study was a phase III study evaluating the effects of us around loans 30 milligram on depressive symptoms and approximately 151 adult women diagnosed with PPD.

And the Robin study, we saw a statistically significant reduction in depressive symptoms and those around loading arm compared to placebo at day 15, the primary endpoint.

As well as day three day eight a 21 day 45.

Additionally, as around loan was well tolerated in the study with a safety profile consistent with what we've seen across the totality of the program.

The Skylark study incorporates the learnings from the Robin study and was developed as a placebo controlled phase III clinical trial evaluating two week courses around loan and women with PPD with an additional short term follow up.

Jim Daugherty: First, the dose. The Skylark study is evaluating a 50 milligram dose of the round lung, whereas the round lung 30 milligrams was used in the Robin study. Second, the Skylark study is larger than the Robin study. As a reminder, the target enrollment for the Skylark study is 200 participants. Third, the Skylark study enrolled patients with PPD who were within 12 months postpartum rather than limiting enrollment to those within six months postpartum. This change casts a wider net for enrollment, but patients are meaningfully different. We recently announced in March that enrollment in the Skylark study has been completed.

Jim Daugherty: We believe that the trial's primary endpoint, the change from baseline as measured by the MD total score at day 15, is a valuable measure for this study and population, as shown in other studies across the program. Specifically, we believe that achieving statistically significant separation from placebo at day 15 with a tolerability profile consistent with that seen in other studies with ziratolone, would constitute success in the Skylark study. We believe these kinds of results, including a rapid reduction in depressive symptoms with a short two-week course of treatment in women with PPD, would support a target profile for ziratolone that would be meaningful in addressing unmet needs for women with PPD.

Notably the Skylark study differs from the Robin study in three key areas.

The dose the Skylark study is evaluating a 50 milligram dose is around loan whereas around loan 30 milligrams was used in the Robin study.

Second the Skylark study is larger than the Robin study as a reminder, the target enrollment for the Skylark studies 200 participants.

Third the Skylark study enrolled patients with PPD, who are within 12 months postpartum rather than limiting enrollment to those within six months postpartum.

This change casts a wider net for enrollments, but patients are meaningfully different we recently announced in March that enrollment in the Skylark study has been completed.

We believe that the trial's primary endpoint the change from baseline as measured by the MD <unk> total score at the 15 is a valuable measure for this study and population as shown in other studies across the program.

Specifically, we believe that achieving statistically significant separation from placebo at day 15, with a tolerability profile consistent with that seen in other studies with surround alone would constitute success in the Skylark study. We believe these kinds of results, including a rapid reduction in depressive symptoms with a short two week course of treatment.

And women with PPD with support of target profile for us around them that would be meaningful and addressing unmet needs for women with PPD.

Additionally, based on our conversations with the FDA to date, we believe statistical significance at day 15 in the Skylark study along with the Robin study and safety data from the entire is around the program.

Jim Daugherty: Additionally, based on our conversations with the FDA to date, we believe statistical significance at day 15 in the Skylark study, along with the Robin study, and safety data from the entire Zoranlin program, would support the associated NDA filing and PPD we've planned for early 2023. I will also point out that because PPD often presents very similar to MDD with elevated anxiety, we are encouraged by the positive results we've seen in patients with MDD presenting with elevated anxiety as a symptom of the depression in the landscape program.

Would support the associated NDA filing in PPD, we've planned for early 2023.

I will also point out that because PPD often presents very similar to MDT with elevated anxiety. We are encouraged by the positive results we've seen in patients with Mds presenting with elevated anxiety as it is.

Symptom of the depression in the landscape program.

Most importantly, we believe the Skylark study can positively contribute to the body of evidence that we have assembled for us around London PPD, so that if a <unk>.

Jim Daugherty: Most importantly, we believe the Skylark study can positively contribute to the body of evidence that we have assembled for xyranolone and PPD, so that if xyranolone is improved, moms with PPD and their doctors can be informed and empowered in assessing xyranolone as a treatment option for PPD. We look forward to updating you on the top-line results of the Skylark study mid-year and providing more detail on our planned associated MDA filing for the surrounding PPD.

<unk> has improved moms with PPD and their doctors can be informed and empowered and assessing the railroad as a treatment option for PPD.

We look forward to updating you on the top line results of the Skylark study mid year and providing more detail on our planned associated NDA filing was around living in PPD.

I'm also excited to share that we've completed our clinical pharmacology studies with the railroads, including a human abuse potential study.

Jim Daugherty: I'm also excited to share that we've completed our clinical pharmacology studies with the Rattlers, including a human abuse potential, or HAP, study. In the HAF study, doses of Zoranlin representative of the planned target range of 30 to 60 milligrams were significantly less preferred than alprazolam at either 1.5 or 3 milligrams by recreational depressant users, the standard population for this type of trial.

In that study doses around loan representative of the planned target range of 30% to 60 milligrams were significantly less preferred than alprazolam at either one five or three milligrams by recreational depressant users. The standard population for this type of trial.

Jim Daugherty: We plan to present the data from this study at the College on Problems of Co-dependence annual meeting in June. We also look forward to sharing several exciting presentations of data from Coral, Shoreline, and the totality of the Landscape and Nest Clinical Development Programs at the upcoming American Society of Clinical Psychopharmacology Annual Meeting, also in June. I'm proud of our work with Zaratulin, and I believe the progress we've made with this important product candidate demonstrates our commitment to delivering life-changing brain health medicines so every person can thrive. I look forward to providing more updates on Zoranlan in the future.

We plan to present the data from this study at the college on problems of drug dependence annual meeting in June .

I also look forward to sharing several exciting presentations of data from coral shoreline and the totality of the landscape in <unk> clinical development programs at the upcoming American Society of clinical Psychopharmacology annual meeting also in June .

I am proud of our work with <unk> and I believe the progress we've made with this important product candidate demonstrates our commitment to delivering life changing greenhouse medicines. So every person can thrive.

I look forward to providing more updates on is around one in the future.

Now I'd like to discuss the progress in our neuropsychiatric franchise led by Sage 718, our lead NMDA receptor.

Jim Daugherty: Now I'd like to discuss the progress in our neuropsychiatric franchise, led by SAGE 718, our lead NMDA receptor positive allosteric modulator, that is a potential oral therapy for disorders where impairment of cognition is one of the main drivers of disability. As a reminder, SAGE 718 was granted Fast Track designation by the FDA as a potential treatment for cognitive impairment in Huntington's disease, or HD, which is an important benefit in our development efforts to bring this therapy to patients.

Positive allosteric modulator that as a potential oral therapy for disorders, where impairment of cognition is one of the main drivers of visibility.

As a reminder, sage seven <unk> was granted fast track designation by the FDA as a potential treatment for cognitive impairment and huntington's disease, or HD, which is an important benefit in our development efforts to bring this therapy to patients.

In addition to exploring the use of Sage seven 1 million HD. We are also evaluating its treatment potential for patients with mild cognitive impairment due to Parkinson's disease or PD.

Jim Daugherty: In addition to exploring the use of SAGE 718 in HD, we are also evaluating its treatment potential for patients with mild cognitive impairment due to Parkinson's disease, or PD, and patients with mild cognitive impairment and mild dementia due to Alzheimer's disease or AD.

And patients with mild cognitive impairment and mild dementia due to Alzheimer's disease or <unk>.

Starting with page 708, an HD. We are currently enrolling the dimension study placebo controlled phase III study of Sage 708, an HD cognitive impairment.

Jim Daugherty: Starting with Phase 718 in HD, we are currently enrolling the Dimension Study, a placebo-controlled Phase 2 study of Phase 718 in HD cognitive impairment. Additionally, we recently announced that we have initiated the Surveyor Study, our second phase 2 study of SAGE 718 in HD cognitive impairment. We designed the dimension study to be robust with a target enrollment of 178 patients with HD, cognitive impairment, that we expect to enroll across 40 clinical sites. Given the tremendous unmet global need in treating HD, we believe that there is a unique urgency to deliver an efficacious, safe therapeutic for patients with HD cognitive impairment.

Additionally, we recently announced that we have initiated the surveyor study our second phase two study of Sage 708, an HD cognitive impairment.

We designed the dimension study to be robust with a target enrollment of 178 patients with HD cognitive impairment that we expect to enroll across 40 clinical sites.

Given the tremendous unmet global need in treating HD. We believe that there is a unique urgency to deliver an efficacious safe therapeutic for patients with HD cognitive impairment.

Jim Daugherty: As we previously stated, if the dimension and surveyor studies generate robust and compelling data, then we will consider the opportunity to engage with regulators to identify a potential path forward to expeditiously bring SAGE 718 to HD patients in need. Turning to our progress in evaluating SAGE 718 for patients with mild cognitive impairment due to PD. We recently announced the initiation of the PRECEDENT study, which is a Phase II placebo-controlled study of SAGE 718 in patients with mild cognitive impairment due to PD, and acts as a follow-on study to the Open Label Paradigm Study, in which SAGE 718 showed a positive impact on multiple domains of cognition in patients in that study.

As we've previously stated if the dimension and surveyor studies generate robust and compelling data and we will consider the opportunity to engage with regulators to identify potential path forward to expeditiously bring sage 708 to HD patients in need.

Turning to our progress in evaluating evaluating sage seven eight for patients with mild cognitive impairment due to PD.

We recently announced the initiation of the precedent study, which is a phase II placebo controlled study of Sage 708 in patients with mild cognitive impairment due to PD and.

It acts as a follow on study to the open label paradigm study.

Sage 708 showed a positive impact on multiple domains of cognition and patients in that study.

Finally, we are advancing our efforts to evaluate stage seven money in patients with mild cognitive impairment and mild dementia due to <unk>.

Jim Daugherty: Finally, we are advancing our efforts to evaluate Stage 718 in patients with mild cognitive impairment and mild dementia due to AD. Following the positive results from the Open Label Luminary Study, in which patients with mild cognitive impairment and mild dementia due to AD, who were on SAGE 718, experienced improved performance from baseline on multiple tests of cognitive function.

Following the positive results from the open label Luminary study in which patients with mild cognitive impairment and mild dementia due to AEP, who are on stage seven months eight experienced improvement and improved performance from baseline on multiple tests of cognitive function.

Jim Daugherty: We are on track with our plans to initiate a placebo-controlled Phase 2 study with SAGE-718 in patients with mild cognitive impairment and mild dementia due to AD in late 2022. I would also like to spotlight data that we presented at recent medical meetings and scientific congresses that underscore the potential for our SAGE 718 program. In March, we presented data at the ADPD 2022 Advances in Science and Therapy International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders, showing that SAGE 718 was associated with improvements on multiple tests of executive functioning and learning and memory in patients with MCI due to PD in the Open Label Phase II Paradigm Study Part A. Additionally, in April, we presented data from the Phase II Luminary Study that showed SAGE 718 was generally well-tolerated and associated with improvements on multiple tests of executive function and learning and memory in patients with MCI and mild dementia due to AD at the 74th Annual Meeting of the American Academy of Neurology.

We are on track with our plans to initiate a placebo controlled phase III study with Sage 718 patients with mild cognitive impairment and mild dementia due to a D. In late 2022.

I would also like to spotlight data that we presented at recent medical meetings and scientific Congresses that underscore the potential for our Sage 708 program.

In March we presented data at the <unk> 2020 to advances in science and therapy International Conference on all timers in Parkinson's diseases and related neurological disorders.

Showing that Sage 718 was associated with improvements on multiple tests and executive functioning in learning and memory and patients with Mci due to PD in the open label Phase II paradigm study part a.

Additionally in April we presented data from the Phase III Luminary study that showed Sage 708 was generally well tolerated and associated with improvements on multiple tests of executive function and learning and memory and patients with Mci and mild dementia due to 80 at the 74th annual meeting.

The American Academy of Neurology.

Jim Daugherty: With these presentations at important scientific forums, we're proud that the SAGE 718 program has generated positive reactions from the scientific community regarding its unique potential to be developed to treat brain health disorders, where impairment of cognition is one of the main drivers of disability. We are excited about the tremendous progress made with our Sage 718 program and look forward to providing updates as they become available. Now I'd like to highlight the advancements made in our neurology franchise, led by SAGE-324, a next-generation positive allosteric modulator of GABA-A receptors, which we believe holds significant potential in the treatment of neurological conditions like essential tremor, or ET.

With these presentations at important scientific forums, we're proud that the Sage 700 program has generated positive reactions from the scientific community regarding its unique potential to be developed to treat brain health disorders, where impairment of cognition is one of the main drivers of disability.

We are excited about the tremendous progress made with our stage seven Monday program and look forward to providing updates as they become available.

Now I'd like to highlight the advancements made in our neurology franchise led by Sage <unk> Q4, and next generation positive allosteric modulator of Gaba a receptors, which we believe holds significant potential in the treatment of neurological conditions like essential tremor ODT.

Jim Daugherty: As a reminder, Stage 324 is being developed as part of our collaboration with Biogen. Based in part on the positive data from the Kinetic Study, we recently started enrollment in the Phase 2B Kinetic 2 Dose Ranging Study, evaluating Phase 3 to 4. Kinetic-2 is designed to optimize the dose and frequency of SAGE-324 in ET.

As a reminder, stage <unk> four is being developed as part of our collaboration with Biogen.

Based in part on the positive data from the kinetics study. We recently started enrollment in the phase two b kinetic two dose ranging study evaluating phase III for <unk>.

Kinetic two is designed to optimize the dose and frequency of stage through Q4 and ETE.

Jim Daugherty: We also shared the study design for our planned Phase 2 Long-Term Open Label Safety Study with SAGE 324 and HEE this morning. This study is designed to assess the long-term safety and tolerability of SAGE 324. Our plan is for this to be a multi-year study with the incidence of treatment emergent adverse events as the primary endpoint. More details are available on slide 45 of the corporate deck on our website. To close, I believe we have made important progress across our pipeline throughout the first quarter, leaving us well positioned for focused execution in 2022 and beyond. Now I'll turn the call over to Kimi for you of our financials. Kimi?

We also shared the study design for our planned phase two long term open label safety study with Sage through Q4 in EP.

This morning.

This study is designed to assess the long term safety and Tolerability of State Street.

Our plan is for this to be a multiyear study the incidence of treatment emergent adverse events as the primary endpoint.

More details are available on slide 45 of the corporate deck on our website.

To close I believe we have made important progress across our pipeline throughout the first quarter, leaving us well positioned for focused execution in 2022 and beyond.

Now I'll turn the call over to <unk> for a review of our financials Kimi.

Kimi Iguchi: Thanks, Jim. Our financial results for the first quarter of 2022 are detailed in our press release issued this, So I'll only highlight some of the key points. I believe 2022 so far has seen us continue to execute as... Backed by a strong balance sheet and with upcoming milestones, I'm confident that our progress during the first quarter and in the period since then moves us closer to our goal of delivering life-changing brain health medicine and bringing long-term value for patients, communities, and key stakeholders. Our net loss for the first quarter of 2022 was $122.1 million and we ended the quarter with cash, cash equivalents, and marketable securities of $1.6 billion.

Thanks, Tim.

Our financial results for the first quarter of 2022 are detailed in our press release issued this morning. So long we highlight some of the key points here.

I believe 2022, so far has seen us continue to execute as planned.

Backed by a strong balance sheet for upcoming milestones I am confident that our progress during the first quarter and the period. Since then move it closer to that Michael delivering life changing greenhouse medicine.

Long term value for patient communities and key stakeholders.

Our net loss for the first quarter of 2022 with a $122 1 million and we ended the quarter with cash cash equivalents and marketable securities of $1 6 billion.

Turning to operating expenses.

Kimi Iguchi: Turning to operating expenses. R&D expenses increased to $78 million in the first quarter of 2022 compared to $58.1 million for the same period in 2021. The increase in spend was related to advancement of our pipeline beyond Zaranalum, including spending on Stage 324 and our wholly owned pipeline, which includes Stage 78. As a reminder, we have six planned and ongoing Phase 2 studies across our neurology and neuropsychiatry franchise. We're excited to continue advancing programs across our franchises with efficient study designs that allow us to be proactive and predictive in our R&D approach. SG&A expenses increased $46.5 million in the first quarter of 2022 compared to $39.8 million for the same period of 2021.

<unk> expenses increased to $78 million in the first quarter of 2022 compared to $58 1 million for the same period in 2021.

The increase in spend was related to advancement of our pipeline beyond <unk>, including spending on page 24.

Wholly owned pipeline, which include Sage 718.

As a reminder, we had fixed plan ongoing safety study the question on neurology and neuropsychiatry franchises.

Alright excited to continue advancing programs across our franchises.

Patient study designs that allow us to be proactive and predictive and our R&D approach.

SG&A expenses increased $46 5 million in the first quarter of 2022.

Care to $39 eight nine for the same period of 2021.

Kimi Iguchi: The increase is primarily related to hiring employees to support ongoing activities in anticipation of potential future launches of our product candidates. Also notable this quarter, we recorded $20 million in reimbursement from Biogen related to our collaboration and licensing. As you recall, the collaboration included the 50-50 cost sharing in the United States for Xeranolone at Stage 324. The savings from the cost-sharing for Zorana Loan and SAGE 324 enabled us to use our cash on hand to continue to invest in advancing our wholly-owned pipeline in a smart and disciplined way.

The increase is primarily related to hiring in place to support ongoing activity.

Anticipation of potential future launches of our product candidates.

Also notable this quarter, we recorded $20 million in reimbursement from Biogen related to our collaboration and license agreement.

The collaboration includes a 50 50 cost sharing in the United States. Thank you Randall and in case of any 24.

The savings from the cost sharing for Joanne alone in page 24 enables us to use our cash on hand to continue to invest in advancing our wholly owned pipeline smart and disciplined way.

Looking forward, we're reaffirming the financial guidance, we provided earlier this year.

Kimi Iguchi: Looking forward, we're reaffirming the financial guidance we provided earlier this year. We anticipate having cash, cash equivalents and marketable securities of approximately $1.3 billion at the end of 2022. We do not anticipate receipt of any milestone payments from collaborations in 2020.

We anticipate having cash cash equivalents in marketable securities of approximately $1 3 billion at the end of 2022.

We do not anticipate any.

Any milestone payments for collaboration in 2022.

Kimi Iguchi: But we believe that our current cash, cash equivalents, anticipated funding from our ongoing collaborations and potential revenue will support operations into 2025. I believe that we're well positioned to continue the focused execution we've demonstrated throughout the beginning of this year. At Sage, we pride ourselves on being courageous, innovative, and efficient across everything we do, always with line of sight on how this work can benefit patients. I look forward to providing additional updates on our progress throughout this year. I'll now turn it over to Helen to handle Q&A with the operator. Helen?

But we believe that our current cash cash equivalents anticipated funding from <unk>.

Ongoing collaborations and potential revenue will support operations into 2025.

I believe that we're well positioned to continue this focused execution, we've demonstrated throughout the beginning of this year.

At page, we pride ourselves on being courageous innovative and efficient request to everything we do always have line of sight on how this work can benefit patients.

I look forward to providing additional updates on our progress throughout this year.

I'll now turn it over to Howard to have a Q&A with Cowen.

Alan.

Helen Rubenstein: Thanks, Kimi. Before I turn it over to the operator, I'll ask that you limit yourself to one question. If you have an additional question, please feel free to return to the queue. Now, I'll turn it over to the operator to handle Q&A. Operator? and a question for me. [inaudible] on your telephone.

Thanks, Kenny before I turn it over to the operator I'll ask that you limit yourself to one question. If you have any additional question. Please feel free to return to the queue now I'll turn it over to the operator to handle Q&A operator.

To ask a question you need to press star one on your telephone.

What drove the question press the pound key.

Please.

Compile the Q&A roster.

Our first question will come from the line of Laura Chico from Wedbush. Your line is open.

Operator: I will withdraw the question, and Biology Compadre. This question will come from the line of Laura Chico. Hey, good morning, guys.

Laura Chico: Thanks for taking the question. I guess one question on Skylark, just wondering if you could remind us on the clinical rationale for extending that eligible window to 12 months for a depressive episode. I realize that this probably facilitates enrollment, but from a scientific perspective, how does this affect the heterogeneity of your enrollment population?

Good morning, guys. Thanks for taking my question I guess one question on Skylark.

Just wondering if you could remind us on the clinical rationale for extending that eligible window to 12 months, where depressive episode I realize it's probably facilitates enrollment but from a scientific perspective, how does this affect the heterogeneity of your enrollment population. Thank you.

Hey, Laura Thanks for the question really appreciate it but we're really excited by the Skylark studied as Jim highlighted in the call. It really is a repeat of the Robin study with a couple of notable changes the 50 milligram.

Unknown Speaker: Thank you. Hey, Laura, thanks for the question. I really appreciate it.

Change the bigger and which is important and as you as you highlighted.

Seeing women with depression out to 12 months versus six months, they really arent that different and Jim you want to just highlight that.

Rationale.

Unknown Speaker: Look, we're really excited by the Skylark study. And as Jim highlighted in the call, it really is a repeat of the Robin study with a couple notable changes, the 50 milligram change, the bigger end, which is important. And as you as you highlighted, seeing women with depression out to 12 months versus just six months, they really aren't that different. And Jim, you want to just highlight that rationale?

Absolutely.

Laura as you mentioned and certainly gives us a wider net for patients and enrollment study, but importantly.

The case that women with PPD have onset of PPD sometime between the third time that sort of the first six months, but the symptoms persist then we've known that for some time so.

In our.

Estimation, it really isn't changing the population all that much. It just gives a wider set of women the opportunity to participate in the trial.

Thanks, guys.

Thanks, Laura.

Jim Daugherty: Yeah, absolutely. And Laura, as you mentioned, it certainly gives us a wider net for patients enrolled in the study. But importantly, you know, it's the case that women with PPD have onset of PPD sometime between the third trimester of the first six months, but the symptoms persist.

Jim Daugherty: And we've known that for some time. So in our estimation, it really isn't changing the population all that much. It just gives a wider set of women the opportunity to participate.

Our next question comes from the line of same.

Unknown Speaker: In the trial. Thanks guys, and Laura. Question from front line of Yasmeen Rahimi from Piper Center. Hi, yes, this is Lauren on pre-ad mean.

Rahimi from Piper Sandler Your line is open.

Hi, Yes. This is Lauren on creatinine, thanks for taking my question.

So looking across the landscape studies when you look into the safety profile of <unk> ran alone what rates are <unk>. So.

Unknown Speaker: Thanks for taking my question. So looking across the landscape studies, when you look into the safety profile for xeranolone, what rates of somnolence were you seeing? And what do you consider mild, moderate and severe percentage wise?

So are you seeing and what do you consider mild moderate and severe percentage wise and then kind of a follow up to that do you see similar rates of final interpretation in patients with and without anxiety. Thank you.

Unknown Speaker: And then kind of a follow up to that, do you see similar rates of somnolence and sedation in patients with and without anxiety? Thank you. Yeah, Lauren, thanks for the question. Please say hi to Yaz for us.

Yeah Lauren Thanks for the question. Please say hi to you guys for us so.

Barry Greene: So, you know, if we step back, what we're seeing is an incredibly broad therapeutic index, Luzeranilone. Jim highlighted the efficacy profile, the rapid reduction of depression and anxiety without any impact to sleep, the long duration of effect, and a really well-tolerated profile. Keep in mind that in MDD patients, PPD patients, with or without anxiety, there's often a challenge for them sleeping, and many of them have sleeping, so having some degree of somnolence is actually a benefit to these patients.

If we step back what we're seeing is an incredibly broad therapeutic index was around alone Jim highlighted.

The efficacy profile of the rapid reduction of depression, and anxiety without any impact fleet, the long duration of effect and it really well tolerated profile keep in mind that in.

And the MDT patients PPD patients with or without anxiety. There is often a challenge for them sleeping and many of them have sleep aid so having some degree of somnolence as actually a benefit to these patients Jim you want to talk about rates.

Jim Daugherty: Jim, you want to talk about rates? Yeah, absolutely, Barry. And of course, now that we have the entire landscape program assembled, of course, we, we have the ability to measure somnolence and sedation in the efficacy trials, which we spent a lot of time talking about. These are also metrics that are included in the clinical pharmacology trials, for example. And so we have the ability to look at sedation and somnolence rates across multiple doses.

Yeah, absolutely Barry and of course now that we have.

The entire landscape program assemble and of course, we have the ability to measure the five months since sedation and the efficacy trials, which we spent a lot of time talking about these are also metrics that are included in the clinical pharmacology trials for example, and so we have the ability to look at.

<unk> some loans rates across multiple doses and so of course as we've talked about before rates are dose dependent but I do think probably the range to quote would be somewhere in the in the teens for some months, depending on the trial low teens to high teens in other trials depending on.

Jim Daugherty: And so of course, as we talked about before, rates are dose dependent. But I do think probably the range quote would be somewhere in the, in the teens for somnolence, depending on the trial, low teens to high teens and other trials, depending on specific trials, specific dose. And that we think is consistent with the mechanism of action and consistent and compares quite well with the rates of safety and somnolence associated with current standard of care. And I will highlight that to keep in mind that you are not seeing the stigmatizing side effects often seen with antidepressants, things like weight gain, sexual dysfunction.

Specific trials specific dose and that we think is consistent with the mechanism of action and consistent.

<unk> compares quite well with the rates we've taken some months associated with current standard of care Telepresence and I will highlight that to keep in mind that we're not seeing the stigmatising side effects, often seen with antidepressants things like weight gain sexual dysfunction, as we put up with coral you see a significant amount.

Jim Daugherty: And as we report out of Coral, you see a significant amount of GI upset with antidepressants, too. And we don't have those those side effects, which often lead to compliance challenges. Perfect.

Upset with antidepressants too and we don't have those.

Those side effects, which often lead to compliance challenges.

Perfect. Thank you.

Our next question comes from the line of Jay <unk>.

Unknown Speaker: Thank you. Plan of Jay Olson from Oppenheimer. Oh hey guys, congrats on the process, the progress, this is Matt on for Jay and appreciate you taking our questions. So we were just curious about any physician feedback that you received at AAN on page 718. Particularly curious how they view the patient reported outcomes data in early HD patients along with any feedback on luminary, that would be great, thank you. Matt, thanks. Appreciate it.

And from Oppenheimer. Your line is open.

Hey, guys congrats on the process.

Progress this is Matt on for Jay.

You're taking your questions.

So we were just curious about any physician feedback that you received.

At AAN on page seven one at <unk>.

Particularly curious how they view the patient reported outcomes data in early HD patients along with any feedback on luminaries that would be great. Thank you.

Hey, Matt Thanks, I appreciate it.

Barry Greene: And please send our best to Jay. And really appreciate the congratulatory note on starting a rolling submission. That's a big deal, and we're really proud that we hit our guidance and started the rolling submission. We can say that what was encouraging at AAN with SAGE 718 is when Aaron Honig presented the data, both in terms of live presentation and the poster session. It was probably the most crowded presentations and one of the most exciting things presented at AAN. His poster was packed, and the rooms were mobbed with presentations.

Please send our best to Jan and really appreciate the congratulatory note on starting the rolling submission Thats, a big deal and we're really proud that we hit our guidance we started the rolling submission.

We can say that.

What was.

Encouraging at AAN.

With Sage 718 is when Erin <unk> presented the data.

Both into slide presentation of the post recession. It was it was probably the most crowded presentations and one of the most exciting things presented at AAN.

His poster was packed in the rooms were mobbed with presentations I can say that.

The feedback we saw from those attending the physicians attending and other health care providers was incredibly encouraging as you.

Chris Benecchi: The feedback we saw from those attending, the physicians attending and other healthcare providers, was incredibly encouraging. As you know, what's gone on in this world, our amyloid hypothesis and other approaches, we really haven't seen an opportunity for a drug to improve cognition. And there was a lot of excitement with the data presented both in Alzheimer's and Parkinson's. Chris, you were there.

You know what's gone on in this world are amyloid hypothesis and other approaches we really haven't seen an opportunity for a drug to improve cognition and there was a lot of excitement with the data presented both in Alzheimer's and Parkinson's Christopher There do you want to talk a little bit more about what you've heard personally yes. So so personally there was a great deal of excites.

Chris Benecchi: Do you wanna talk a little bit more about what you heard personally? Yeah, so personally, there was a great deal of excitement, as Barry mentioned. I think in standing back and reflecting on it, I think from a clinician's perspective, they really understand the impact that this can have on the patients that they see day in and day out. And right now, there are not other options available for patients, whether they have Huntington's disease, Parkinson's disease, or Alzheimer's disease, living with mild cognitive impairment. And what we heard is there really is nothing mild about mild cognitive impairment.

As Barry mentioned I think in standing back and reflecting on it I think from a clinician perspective.

Really understand the impact that this can have on the patients that they see day in and day out and right now there are not other options available for patients whether they have huntington's disease. Parkinson's disease are all time has to be living with mild cognitive impairment.

What we heard is there really is nothing mild about mild cognitive impairment. These are patients who are really suffering from the effects associated with cognitive impairment and loss of independence.

Chris Benecchi: These are patients who are really suffering from the effects associated with cognitive impairment and a loss of independence. It's really important as we think about going forward, the difference that we can make in these patients with SAGE 718, because those moments are precious for patients that are living with these diseases. As someone who has a dad with Parkinson's disease, with mild cognitive impairment, those moments are few, and families and friends would like to get that.

It's really important as we think about going forward. The difference that we can make in these patients with sage 708, because those moments of precious for patients that are living with these diseases as someone who has a dad with Parkinson's disease with mild cognitive impairment.

Moments are few and families and friends, we'd like to get those back.

Got it thank you so much.

Thanks, Matt.

Our next question comes from the line of Cory <unk> from Jpmorgan. Your line is open.

Unknown Speaker: Got it. Thank you so much. Thanks Matt, on the line of Corey Kasimov, Hey guys, this is Tiffany on for Corey. Just one to add on 718, can you just talk about the trial design differences in the recently initiated phase two Parkinson's study versus the prior paradigm study? And what are you kind of hoping to see with this? And also any sense of cadence for updates?

Hey, guys. This is <unk> on for Corey just one.

71, <unk> can you just talk about the trial design differences and recently initiated phase two <unk> study versus the prior paradigm study what are you kind of hoping to see with US and also any sense of cadence for update thank you.

Hey, Tiffany thanks for the question. So I'll do the uptake part first and then ask Jim to talk about the different trial designs and why we did such robust chosen. So the trials are as we highlighted on the call are up and running.

Unknown Speaker: Thank you. Hey, Tiffany, thanks for the question. So I'll do the update part first, and then ask Jim to talk about the different trial designs and, you know, why we did such robust trials. So the trials are, as we highlighted in the call, are up and running. As we like to do, we want to get sites activated and see what the trial accrual looks like. And then once we're comfortable, we'll provide clear guidance on when we believe the trial will come to fruition. But Jim, you want to talk about the different designs and how we size them? Absolutely, Barry.

We'd like to do we want to get sites activated and see what the <unk>.

Trial accrual looks like and then once we're comfortable we'll provide clear guidance on when we believe the trial will come to fruition, but Jim you want to talk about the different designs and how we size them absolutely Barry yeah. So the precedent study represents what will be the first placebo controlled study for Sage 708 in patients with cognitive impairment due to Parkinson's.

Jim Daugherty: Yeah, so the precedent study represents what will be the first placebo-controlled study for SAGE-718 in patients with cognitive impairment due to Parkinson's disease. And of course, as you know, we think about this as a concept of serially de-risking. So the earlier study in Parkinson's disease was a small open-label study designed to give us both an early look at whether or not SAGE-718 was providing benefit to this patient group, but also the opportunity to really hone the safety sorry, the study design for the precedent study. So the precedent study, unlike the earlier study, is a 42-day duration dosing. So the dosing period is longer in precedent.

These.

Of course as you know we think about this as a concept of cereal derisking. So the earlier study in Parkinson's disease was a small open label study designed to give us both an early look at whether or not stay seven when he was providing benefit to this patient group, but also the opportunity to really hone the safety sorry, the study design.

Jim Daugherty: Of course, it is a placebo-controlled study, and then we'll have a follow-up period after the dosing period. So three months dosing, placebo-controlled study. Great, thanks, and Stephanie. Brian Abrahams, Ritu Baral, Kallan, Good morning, everyone.

For the precedent study so the precedent study. Unlike the earlier study is a 42 day duration dosing. So the dosing period is longer and precedent.

Of course, it is a placebo controlled study and then we'll have a follow up period. After the dosing period. So three months dosing placebo controlled study.

Great. Thanks.

Thanks, Stephanie.

Our next question will come from the line of <unk> from Cowen you may begin.

Good morning, everyone. Thanks for taking the question.

Unknown Speaker: Thanks for taking the question. I wanted to ask about the rolling submission and what you're going to be asking for. I guess, one, Barry, can you go through just the outstanding items before you guys can submit the clinical module and what the most important gating steps are to that? And second, just given you're going after sort of a broad population, you outlined treatment naive, but also patients who were sort of resistant to previous treatment attempts, whether through adherence or efficacy. What will you be asking for on the label?

Wanted to ask about the <unk>.

Our rolling submission and and what Youre going to be asking for I guess one.

Can you Gary can you guys give just the outstanding items before you guys can submit the clinical module and what the most important gating.

These steps are to that and second just given you're going after sort of a broad population you outlined your treatment naive.

Barry Greene: And what sort of benzo black boxes do you think will translate, especially that most recent one? Thanks. Yeah, Ritu, thanks for the question. So a couple things.

But also patients who are sort of resistant previous previous treatment attempts to weather through adherence or efficacy.

Will you be asking for on the label and what sort of.

Denzel Black boxes, do you think will translate especially that most basically thanks.

Yes, ritu. Thanks for the question. So a couple of things, let's start with the NDA Rolling submission and then we can talk about what we'll be looking for so as said today were very excited to have started the rolling submission with the non clinical section as Jim highlighted all the pharmacology work is done and all of the clinical studies are done so it's really a matter of <unk>.

Barry Greene: Let's start with the NDA rolling submission, and then we can talk about what we'll be looking for. So as you saw today, we're very excited to have started the rolling submission with the non-clinical section. As Jim highlighted, all the pharmacology work is done, and all of the clinical studies are done.

The studies.

Going through the QA processes, making sure we have the highest quality submission we will.

Let everybody know when we finished the filing the NDA in the second half of the year and then we will communicate further when the NDA is accepted so there'll be the communication, but I can say that all of the section all the modules are in very good shape, it's really a matter of getting the work done as we've highlighted on previous calls the two items that are getting <unk>.

Barry Greene: So it's really a matter of compiling the studies, going through the QA processes, and making sure we have the highest quality submission. We will let everybody know when we've finished filing the NDA in the second half of the year, and then we'll communicate further when the NDA is accepted. So those will be the communication. But I can say that all of the modules are in very good shape.

We announced the coral study very Excitingly and we're translating the Japanese study into an NDA filing study. So that's a chunk of work that the team is working through but we're well on track to finish in the second half of the year.

Barry Greene: It's really a matter of getting the work done. As we've highlighted in previous calls, the two items that are getting wrapped up, we announced the coral study very excitingly, and we're translating the Japanese study into an NDA filing study. So that's a chunk of work that the team is working through. But we're well on track to finish in the second half of the year.

In terms of in terms of what we're asking for.

It's too early to talk about label specifics or any kind of <unk>.

Warnings.

Barry Greene: In terms of what we're asking for, it's too early to talk about label specifics or any kind of warnings, But, you know, what we are seeing and studying is we have a drug here, xeraniline, for the treatment of MDD and PPD, with or without elevated anxiety. So, that's the kind of discussions we envision having with the agency. You know, in terms of warnings, again, too early to talk about specifics. We'll have some of the typical things in there, you know, don't operate heavy machinery until you know how the drug works, things like that. But we're not sure if we'll have xeraniline-specific issues or warnings or CLASP-like warnings. It's too early to tell.

But what we what we are seeing in studying as we have a drug here's rental for the treatment of <unk>, and PPD with or where that elevated anxiety. So.

That's the kind of discussions we envisioning, having with the agency in terms of in terms of warnings again too early to talk about specifics and we will have some of the typical things in there don't operate heavy machinery and so you know how the drug works things like that.

But we're not sure if we'll have <unk> specific issues were warnings were class like warnings, it's too early to tell and we're certainly going to.

Barry Greene: We're certainly going to, you know, accept certain warnings that are classic, like I just highlighted, and, you know, maybe push back on some others. Because if we're not seeing certain effects, we don't think we should have warnings there. Got it.

Except certain warnings that are classic like I, just highlighted and maybe pushed back and some others because.

If we're not seeing certain effects, we don't think we should of Morningstar.

Got it great. Thanks, I'll get back in the queue.

Unknown Speaker: Great. Thanks. I'll get back in the queue.

Unknown Speaker: Thanks, Ritu. Salveen Richter, from Goldman Sachs. Hi, thanks so much for taking our question. This is Tommy on for Salveen.

Thanks Peter.

Our next question will sign of solving enriched Sir from Goldman Sachs you may begin.

Hi, Thanks, so much for taking our question. This is Tommy on for <unk>, and we wanted to ask about seven <unk>.

Barry Greene: And we wanted to ask about 718. You've seen some interesting results in both Parkinson's and Alzheimer's suggesting a durable benefit beyond the dosing period. And so how are you thinking about the potential dosing regimens going forward? Do you feel like chronic dosing is necessary? Or is there the possibility of shorter or less frequent dosing? Thanks. Yeah, Tommy, great question.

Some interesting results in both Parkinson's and Alzheimer's, suggesting a durable benefit beyond the dosing period and so how are you thinking about the potential dosing regimens going forward.

Do you feel like chronic dosing as necessary or is there the possibility of shorter or less frequent dosing. Thanks.

Yes, Tony Great question appreciate that.

Barry Greene: Appreciate the attention on SAGE 718. So, you know, as Jim highlighted, we, you know, we continue to learn and serial de-risk the studies. We're excited by the efficacy we've seen and by the very, very broad therapy. Again, though, we're talking about really low doses of SAGE 718 as a NMDA PAM. So we do believe that SAGE 718 at this point will be chronically dosed. It's too early to know if there'll be an any kind of dosing breaks, but it doesn't seem to be required because while the effects are durable due to, you know, brain circuitry rewiring, we don't see any kind of tolerability challenges or tachyphylaxis that would warrant any kind of periodic dose or dosage disruption.

Potentially on Sage 718.

Yes.

As Jim highlighted we continue to learn and cereal Derisk. The studies were excited by the efficacy we've seen and by the very very broad therapeutic window, we're talking about really low doses of Sage 718 is.

NMDA Pam.

So we do believe that seed so it's at this point will be will be chronically dosed.

Too early to know if there'll be any kind of dosing breaks, but it doesn't seem to be required because while the effects are durable due to brain circuitry rewiring, we don't see any kind of tolerability challenges or tachyphylaxis that would warrant any kind of periodic dose or doses direction. So right now we believe it's a chronic chronic drug Jim.

Now I'll just buried in that.

Jim Daugherty: So right now, we believe it's a chronic drug. Jim, anything to add? No, just, Barry, that part of what the status studies are designed to do is to give us further information about how the drug's performing with repeat dosing. As Barry said, our current assumptions are chronic dosing, and we have enough diversity amongst clinical trials to give us a little bit better sense of how the drug performs specifically. And so I think this is just part of the process.

Part of what the.

Set of studies are designed to do is to give us further information about how the job's performing with repeat dosing as Barry said, our current assumptions are chronic dosing.

But we have enough diversity amongst clinical trials give us a little bit better sense of how the drug performs specifically.

And so I think this is just part of the process. So to date, we have data from relatively short duration dosing.

14 days, but as we go to the next round of studies will have longer duration dosing and really get more detailed into the specific questions about how 700 it can be delivered.

Jim Daugherty: So up to date, we have data from relatively short duration dosing, 7 to 14 days. But as we go to the next round of studies, we'll have longer duration dosing and really get more detailed into the specific questions about how 718 can be delivered. Thank you. Thanks, guys, by Akash Tiwari.

Thank you.

Thanks, Tony.

Our next question comes from the line of.

Josh Tomorrow from Jefferies you may.

Again.

Hi, This is the nature of our cash and thank you for taking our question.

Unknown Speaker: Hi, this is Leo for Akash. Thank you for taking our question. Previously, you mentioned you have VBAs with payers and payers could use ICD-9 or 10 code to monitor the use of Zoranolone at the population level. How should we think about the mechanics of revenue recognition for Zoranolone?

You mentioned, you have ppas with payers and payers could ICT Niall tempo can monitor the cadence obviously ran alone at the population level, how should we think about the mechanics of revenue recognition ran alone.

Unknown Speaker: Do you set a reserve for potential callbacks from the payers if patients use more courses of Zoranolone in one year? And in addition, when you have conversations with payers, do they mention any potential requirement for prioritizations or requirement of patients to try generic antidepressants first? And then does VBA actually lower the payers' requirement for prescribing Zoranolone? Thank you. Yeah, thanks, Leo. Let me let me try to unpack a couple of those those questions.

That that reserve for potential claw back from the payers patients use more.

What caused that delta rattling around here.

And when you have conversations with payers do they Nash any potential requirements for privatizations or a client and a patient could try generic that get back to the first Dan DBA actually lower to pay out a client that before prescribing is around thank you.

Yes, Thanks, Luo, let me, let me try to unpack a couple of those questions and then I'll ask Tim to talk about.

Barry Greene: And then I'll ask Kimi to talk about Revenue Rec and then Chris to talk about sort of what we're hearing from payers. So if I step back, we've articulated that part of our commercialization strategy is leaning in with proactive value based agreements. Our ask of payers is that if a health care provider writes a script that that patient deserves Zoranolone and gets Zoranolone without step throughs and without prior auth. It's very important, given the features of Zoranolone, that if someone's depressed, they get Zoranolone quickly so they can get better in two or three days.

Revenue rack and then Chris can talk about sort of what we're hearing from payers. So if I step back we've articulated that part of our commercialization strategy.

Leading in with proactive value based agreements or <unk>.

Payers is that if a health care provider writes a script patient deserves around gets around alone without step throughs and without prior off its very important given the features that was around on that if someone's depressed. They gets around quickly. So they can get better in two or three days everyday to these patients is a lifetime in matters, so waiting weeks to get better.

Barry Greene: Every day to these patients is a lifetime and matters. So waiting weeks to get better is just not okay. And as we know from health and health economic perspective, under treated or delayed treatment results in long term comorbidities and costs. So getting patients better fast and keeping them better is critical. And our agreement or our ask with payers is that, again, if a script comes in, it gets filled without a lot of hurdles.

Not okay and.

As we know from health and health economic perspective under under treated or delayed treatment results in long term comorbidities and costs, so getting patients better fast and keeping them better is critical and our agreement our app with Payors is that again, if the script comes in it gets filled without a lot of hurdles are.

Barry Greene: Our give for that is to understand what challenges payers might have. So, for example, a payer might be nervous about epidemiologically how many of their patient population is suitable for seranolone. We can protect them if it goes over that.

Give for that is to understand what challenges payers might have so for example, a payer might be nervous about epidemiologically. How many of their patient population is suitable for <unk>. We can protect them. If it goes over that they might be concerned that their patient population instead of needing one to two two of course through the course of the year.

Barry Greene: They might be concerned that their patient population, instead of needing one to two TUI courses in the course of a year, which they budgeted for, might need three or four or five, which they didn't budget for. And what they want is budget certainty. So we can protect them against that.

Which they budgeted for might need three or four five which they didn't budget for and what they want is budget certainty. So we can protect them against that and every payer conversations unique and I can say, they're going incredibly well can be do you want to talk about sort of Rev. Rec and how that might work in biogen's hands and then Chris can talk about some of the feedback.

Barry Greene: And every payer conversation is unique, and I can say they're going incredibly well. Kimi, do you want to talk about sort of Rev-Rec and how that might work in Biogen's hands? And then Chris can talk about some of the feedback we're actually hearing from payers at this time. Great, sure, thanks.

Actually hearing from payers at this time.

Sure. Thanks.

Kimi Iguchi: So let me just give you a little color on how to think about the revenue from the perspective of the P&L. So, you know, currently our collaboration R&D expense and SG&A expense are all included and recognized in our operating expense line. We net our reimbursements in that line. So that's how it will show until commercial launch. But as we get to commercial launch, if Zaranulon is approved, we expect that our net profit share will be recorded in the profit share revenue line in our P&L. And that profit share revenue line would reflect 50% of the product revenue.

So let me just give you a little color on how to think about the revenue from the perspective of the P&L. So currently.

<unk> and R&D expense and SG&A expense are all <unk>.

Included in recognized in our operating expense line.

Our reimbursement in that line. So that's how it will show until commercial launch, but as we get to commercial launch at their analog is approved we expect that our net profit share will be recorded in the profit share revenue line of our P&L and that profit share revenue line would reflect 50% of product revenue and then.

We would reduce it by that collaboration related SG&A expenses, so that would be in the revenue line.

Kimi Iguchi: And then we would reduce it by the collaboration related SG&A expense. So that would be in the revenue. We'll continue to show the R&D expenses in the R&D line, net of any reimbursement. We'll certainly provide additional clarity as we get closer to launch on exactly how that works. So I'll turn it over to Kristen. Yeah, sure. And I'll take it, Barry.

We'll continue to show the R&D expenses.

R&D line net of any reimbursement.

Well certainly provide additional clarity as we get closer to launch on exactly how that will work.

So I'll turn it over to Chris now.

Chris Benecchi: Leo, thanks for the question. So, so right now, as you might imagine, we are deeply engaged with national and regional payers, as well as PBMs and IDNs. And what we're hearing is that there remains a profound unmet need with respect to the treatment of both MDD and PPD for patients that are that are coming in at the plan level, you know, despite the fact that there's been 35 therapies over the last 30 years, there's not been significant advance that's provided the solution for not only for physicians and patients, but for the payers who are working in this space.

Yeah, sure and I'll take it Barry Thanks.

Thanks for the question. So so right now as you might imagine we are deeply engaged with national and regional payers as well as Pbms and Ibms and what we're hearing is that there remains a profound unmet need with respect to the treatment of both <unk> and PPD.

For patients that are that are coming in as planned level. Despite the fact that there's been 35 therapies over the last 30 years. There has not been significant advanced that's provided the solution for not only for physicians and patients the payers who are working in this space. So now with that said as they step back and they think about treating the patient.

Chris Benecchi: So now with that said, as they step back, and they think about treating this patient population, they also recognize that there are complex comorbidities that these patients often suffer from. Quite often, it's cardiovascular disease or, or other neurological conditions.

Population. They also recognize that there are complex comorbidities that these patients often suffer from quite often its cardiovascular disease or are other neurological conditions and that has real long term cost associated with it for the plans that they need to actually consider as they think about the treatment of this patient population. So when we begin to have discussions around surrender.

Chris Benecchi: And that has real long term costs associated with it for the plans that they need to actually consider as they think about the treatment of this patient population. So when we begin to have discussions around Zoranolone, the idea of a therapy that gets patients better, faster, that's well tolerated, that can be delivered in a short course therapy that doesn't carry those stigmatizing side effects of sexual dysfunction and weight gain that often are determinants of adherence.

The idea of a therapy that gets patients better faster.

Well tolerated that can be delivered in a short course therapy that doesn't carry those stigmatising side effects of sexual dysfunction, and waking and often are determinants of inherent this is a highly attractive therapy for payers and it has been really positive and productive conversations that we initially had and we look forward to continuing on with us.

Thank you very much.

Thanks Lee.

Our next question will come from the line of Paul Matteis from Stifel. You may begin.

Chris Benecchi: This is a highly attractive therapy for payers. And it has been really positive and productive conversations that we've initially had. And we look forward to continuing on with, Thank you very much. Thanks, Leo. Our next question comes from Paul Matteis. Hi, this is James on for Paul.

Hi, This is James on for Paul Thanks for taking the question.

Unknown Speaker: Thanks for taking the question. Maybe just a quick one on regulatory now that the process has kicked off. I guess I'm curious, how are you thinking about redosing?

Maybe just a quick one on regulatory now that the.

The process has kicked off.

I guess I'm curious how are you thinking about re dosing and interline there is restrictions around.

When a patient can be readouts and I guess, how are you thinking about the potential of any sort of restrictions around labeling or anything like that when it comes to re dosing and if there are how that may play out commercially.

Yes, James Thank you for the question on the regulatory pathway and again they were excited to have started the rolling submission. This week. So shoreline will be a critical part of our submission and just to remind everybody what we saw on shoreline.

Unknown Speaker: And, you know, in Shoreline, there is restrictions around, you know, when a patient can be redosed? And I guess, how are you thinking about the potential of any sort of restrictions around, you know, labeling or anything like that when it comes to redosing? And if there are, you know, how that that may play out commercially?

Which is the largest naturalistic study run at MD, where.

Where patients are actually asked after the two week dosing every other week, how theyre doing so.

It's kind of a.

While it's not placebo controlled patients are often asked how theyre doing so we've seen as a majority of patients in the course of your only required one two week course of treatment.

Barry Greene: Thanks. Yeah, James, thank you for the question on the regulatory pathway. And again, you know, we're excited to have started the rolling submission as this week. So Shoreline will be a critical part of our submission. And just to remind everybody what we saw on Shoreline, which is, which is the largest naturalistic study run in MDD, where patients are actually asked after the two week dosing every other week, how they're doing. So it's, it's, it's kind of a, while it's not placebo controlled, patients are often asked how they're doing. So what we've seen is the majority of patients in the course of a year only required one two week course of treatment, and then 80% only required one or two two week course of treatment.

And then 80% only acquired one or two to a course of treatment so in the real world.

That the majority of patients treated.

All require only one or two week courses and of course I explained with Leo's question part of the value based agreements will be providing protections over a couple two week course of treatment.

I don't we don't know exactly how the discussion we'll go we have data up to five <unk>.

<unk> treatment courses.

I have not seen any additive safety with retrieved in fact, the adverse event numerically is actually goes down with each and every recourse. So we've got a good argument to allow re treatment weren't allowed.

As rapidly as Jim already highlighted the pharmacology studies, we've got higher doses extended doses. So there's no reason in the real world that if someone is better after two weeks and then a month later.

<unk> needs. Another treatment. There is no reason why they couldn't get it from a data perspective now.

Go into extreme if the agency were to restrict.

The REIT treatment to a timeframe where only to two two of course is in the course of the year, while we think that's terrible for patients and not the right thing to do it really won't have much of a commercial impact because our commercial estimates are that one to two week course of treatment for the majority of patients.

Barry Greene: So in the real world, we think that the majority of patients treated will require only one or two week courses. And of course, as I explained with Leo's question, part of the value based agreements, we will be providing protections over a couple two week courses of treatment. So I don't, we don't know exactly how the discussion will go. We have data up to five retreatment courses. We have not seen any additive safety with retreat.

And our next question comes from the line of Marc Goodman from Seb Securities You may begin.

Barry Greene: In fact, the adverse event numerically actually goes down with each and every recourse. So we've got a good argument to allow retreatment when allowed, you know, as rapidly as Jim already highlighted. In the pharmacology studies, we've got higher doses, extended doses. So there's no reason in the real world that if someone is better after two weeks, and then a month later, per se, needs another retreatment, there's no reason why they couldn't get it from a data perspective.

Barry Greene: Now, don't go into an extreme, if the agency were to restrict the retreatment to a timeframe or only to two two week courses in the course of a year, while we think that's terrible for patients and not the right thing to do, it really won't have much of a commercial impact because, you know, our commercial estimates are that one to two week courses of treatment for the majority of patients.

Yes.

And thanks for taking my question.

Unknown Speaker: Question from the line of Mark Goodman from SVB Securities, you may begin. And thanks for taking my question. This is really on the line for Mark.

Really on the LIFO Mark.

Unknown Speaker: I'm Ken Grant on the initiation of the Rolling End-Game Submission. So I have a question regarding the Phase II Surveyor Study of Stage 718. So it seems like we have both Huntington's disease and a healthy subject in the study. Can you provide more color on the trial design and what is the rationale of adding the healthy participants as the comparator arm? Thanks. Yeah, Rudy, again, and thank you for the congratulatory note.

Okay.

Susan that the rolling NDA submission.

A question regarding the phase III <unk> study of Sage 718.

I assume 90, how both huntington's disease in healthy subjects in the study.

Can you provide more color on the trial design and what is the rationale, adding housekeep participants as the comparator arm.

Yes, Rudy again, and thank you for the congratulatory note so.

Barry Greene: So, you know, as we're thinking about Huntington's disease, and starting with Huntington's, as everyone's aware, it's an orphan disease, where a drug designed to improve cognition has just not been developed. So we're really forging new regulatory pathways. We believe that the sizing of dimension in the Surveyor Study, in totality, should the data be positive, would give us significant energy to approach regulators for, you know, the fastest way to get the drug to market.

As we're thinking about Huntington disease, starting with Huntington's as everyone's aware, it's an orphan disease, where a drug.

Designed to improve cognition, just not been developed so early forging new regulatory pathways.

Believe the sizing of dimension that severe study in totality should the data be positive will give us significant energy to approach regulators for the fastest way to get the drug to market.

Barry Greene: So as an overall package, that's how we're thinking about the study, the, you know, the numerical, the numerical values and dimension coupled with the real world, the real world evidence in Surveyor. So that's the overall strategy and thought process. But Jim, you want to talk more about Surveyor? Yeah, absolutely, Barron.

As an overall package, that's how we're thinking about the study.

Miracle.

The numerical values and dimension, coupled with the real world.

The real word evidence in severe so that's the overall strategy and thought process, but Jim you want to talk more about severe yes, absolutely bear and Thats, probably the thing to know first about survey or is this is a study where we're beginning to understand how the cognitive measures that we've been studying so far will translate into measures of function.

Jim Daugherty: Probably the thing to know first about Surveyor is, this is the study where we're beginning to understand how the cognitive measures that we've been studying so far will translate into measures of function that are going to be meaningful to patients. And so really, Surveyor is designed to be complementary to the Dimension Study. And what we're trying to do in Surveyor is to understand the linkage between the primary endpoint, which is looking at the components of the composite score from the Huntington's Disease Cognitive Assessment Battery.

To be meaningful to patients and so really surveyor is designed to be complementary to the dimension study and what we're trying to do in surveyor is to understand the linkage between the the primary endpoint, which is looking at the composite score from the Huntington's disease cognitive assessment battery, but many of the tests are quite similar to the <unk>.

Jim Daugherty: But many of the tests are quite similar to the types of tests that we've been studying so far. We want to be able to link that to performance in a variety of real world-based assessments. So that's really the purpose of Surveyor. As you mentioned, there is, in addition to that, a healthy participant group. So there are three arms in Surveyor.

The test that we've been studying so far we want to be able to link that to performance and a variety of real world based assessments. So thats really the purpose of surveyor as you mentioned there is in addition to that.

The participant groups. So there are three arms and survey here. So the subjects from the HD group will be randomized either to say $700 or to placebo. So we get that placebo control.

Jim Daugherty: So the subjects from the HD group will be randomized either to, say, 718 or to placebo. So we get that placebo control looking at the endpoints I was mentioning. But in addition to that, we're including a healthy participant group. And that really is to begin to get some assessments of healthy performance with batteries. So those folks are not being tested with, say, 718, but they are going to be tested with the batteries of cognitive tests and real world endpoints that we're looking at. Got it.

Looking at the endpoints I was mentioning but in addition to that we're including <unk>.

Healthy participant group and that really is to begin to get some assessments of healthy performance with the batteries. So those folks are not being tested with <unk>, but they are going to be tested with the batteries.

Cognitive tests in real World.

Endpoints that we're looking at.

Got it thanks.

Unknown Speaker: Thanks. That's very helpful. Thanks, Rudy. The Question comes to liner.

Very helpful.

Thanks, Larry.

Our next question will come from the line.

Unknown Speaker: Yatin. Suneja from Guggenheim, you may begin. Hey guys, thank you for taking my question. Question on Skylark, can you just talk about the expectation, what feedback have you received from... K.O.R.S. in Council of the Africa Seeds, that... [inaudible] I'm just trying to get a sense of the delta.

So nature from Guggenheim you may begin.

Hey, guys. Thank you for taking my question a question on Skylar can you just talk about the expectation what feedback have you received from the Kols in terms of the efficacy that different for PPD versus MTBE.

Just trying to get a sense of the delta that we should be expecting on the Ham D. And then how would the re dosing work in PPD, which we generally define has been a bit of a temporary.

Barry Greene: And then how would the re-dosing work in PPT, which is generally defined as a little bit of a temporary, of those women. Wanderer, Yeah, thanks for the question. So look, we're excited by the Skylark study. And as we highlighted, we're on track to read that out mid year. We've, you know, Jim highlighted this in the call, we have Robin and a number of other positive studies. And as we highlighted, PPD is very much like MDD with elevated anxieties, depression.

Depression will those women be eligible to get only one dose or could they get an additional dose. Thanks.

Yes. Thanks for the question. So look we're excited by.

The Skylark study and as we highlighted we are on track to read that out midyear.

We have Jim highlighted this in the call.

Barry Greene: So we believe that with a positive scholarly study, and just to be clear, STAT-SIG at day 15, without any surprising side effects, is what we're looking for, for a submittable study for PPD. In terms of redosing, that will really be up to a healthcare provider and the patient. You know, as you said, what's generally believed is that the depressive episode is caused by pregnancy or childbirth. And that what we've seen is that most moms, when given either Zolresso, which we have commercially, or Xeranil in our studies, stay better for a long period of time. If six months, 12 months, 18 months later, they have another depressive episode, that typically gets classified as MDD, and they can be retreated at that point.

We have we have robin in a number of other positive studies and as we highlighted PPD is very much like MPD with elevated anxiety depression. So we believe that with a positive skylark study and just to be clear stat Sig at day 15 without any surprising side effects is what we're looking for for Submental study for PPD in.

A re dosing that will really be up to a health care provider and the patient.

Barry Greene: But more from an MDD diagnosis. Thanks for watching Alphonse & Aline, Ami Fadia Unknown Executive, Ami Fadia, Jay Olson, James Condulis, George Farmer, Sumant Kulkarni, Mike, Hello, guys. Thank you for taking the question. This is Amin or Ani.

As you said.

Whats generally believed is that the depressive.

Episode is caused by pregnancy or childbirth and that what we've seen is that most moms when given either.

<unk>, which we have commercially or is the rental in our studies stay better for a long period of time.

Six months 12 months 18 months later they are another depressive episode that typically gets classified as MD and they can be retreated retreated at that point, but more from an MDT diagnosis.

Thank you.

Our next question will come from the line.

On the <unk> from Needham you may begin.

Okay.

Hello, guys. Thank you for taking the question.

Barry Greene: The question we have is related to, The discussions you have with the payers, you mentioned that so far the discussions that are going on are very positive. I wondered if you engaged in any discussions that were, that the payers were kind of concerned about the priority that you prefer to have compared to what they have in mind, usually the generics and to the recent approved drugs, if you can elaborate on that.

Or.

The question we have is.

Two.

The discussions you have with the payers.

You mentioned that.

So far the discussions that are going on are very positive as bundled if you engage in any discussion that's fair.

<unk>.

It depends right.

Concerned about.

Alright.

<unk>.

Sorry to have compared to what they have in mind.

Usually the generic spend.

The approved drugs.

Doug if.

If you can elaborate on that that would be great.

Yes, thanks for the question so again.

Barry Greene: Yeah, I mean, thanks for the question. So, you know, again, within the context of proactive value-based agreements, the overall overview, we have engaged payers. We're certainly talking about disease state awareness. Some payers have certainly read everything that's been publicly released, so the discussion of Zoran alone and data come up. And Chris highlighted this earlier, but I'll summarize it quickly. What we're hearing from payers is that while depression is no longer a very large category because of the generic nature of available antidepressants, they have recognized, and the words they use is patients cycle through many drugs. It's a problem for them.

Within the context of proactive value based agreements. The overall overview, we have engaged payers.

We're certainly talking about disease state awareness.

Some payers have certainly read everything thats been publicly released so the discussion of <unk> alone and data come up and Chris highlighted this earlier, but I'll summarize it quickly what we're hearing from payers is that while depression is no longer a very large category because of the generic nature of available antidepressants they have recognized.

Barry Greene: Even though it's going from one cheap drug to another, having patient populations that are depressed remain depressed, they recognize leads to longer-term comorbidities. They stay depressed. People that stay depressed have a higher likelihood of cardiovascular events, diabetes, and even infectious diseases. It's been well documented that the depressed population, for example, has a higher prevalence of getting COVID or being hospitalized. All that costs payers.

And the words, they use as patients cycle through many drugs, it's a problem for them, even though it's going from one chief drug to another having patient population that are depressed remained depressed.

Recognized leads to longer term comorbidity, they stay depressed.

People that stay depressed.

Likelihood of cardiovascular events diabetes, and even in infectious disease, and it's been well documented that that debt.

Barry Greene: So what we're hearing from them is, you know, if under the context of value-based agreements, so we're being fair to them, they'll be fair back, they're actually seeing agreement that if a healthcare provider writes a script for Zoran alone, they fill the script. And what we're trying to do, to the extent we can, is we're trying to avoid prior auths, we're trying to avoid step-throughs, because that's the wrong thing to do for patients. Thank you. That was great.

<unk> population for example has a higher prevalence of getting COVID-19 or being hospitalized all that cost payers. So what we're hearing from them is.

If under the context of value based agreements. So we're being fair to them there'll be fair bet, they're actually seeing agreement that.

Health care provider right descriptors around alone they fill the script and what we're trying to do.

The extent, we can as we're trying to avoid prior offs were trying to avoid step throughs, because thats the wrong thing to do for patients.

Thank you.

Yes.

Our next question will come from the line of Gary Markman from BMO capital markets you may begin.

Unknown Speaker: Question on call for the line, Gary Mockman from PMO. Hi, thanks for taking our question. This is Evan Hua, I'm for Gary Nachman.

Hi, Thanks for taking my question, Evan fall off with Gary Nachman.

Unknown Speaker: I just had a question. Would you be able to talk about the timing of PPD and MDD approvals and when that could come? Given that PPD has fast-track designation, could PPD approval come at the same time or even earlier than MDD? Gavin, thanks for the question. So I can give you generalities. And we were we were very much aided by our strategic discussion with the with the agency in the fall of last year.

I just had a question would you be able to talk about timing of PPD and <unk> approvals and when that could come given that <unk> has fast track designation PPD approval will come at the same time or even earlier than MDT.

Gavin Thanks for the question. So I can give you generalities and we were very much aided by our strategic discussion with the <unk>.

Unknown Speaker: Just to remind everybody, we had highlighted that, When we started the Landscape and Nets programs, we had alignment with the agency that we needed one more positive study for a file to package. Waterfall was that positive study. Following Waterfall, we met with the agency in the fall of last year.

Agency in the fall of last year, just to remind everybody.

We had highlighted that.

When we started the landscaping nurse programs, we have alignment with the agency that we needed one more positive study for a file of the package.

Waterfall was that positive study following waterfall, we met with the agency in the fall of last year and the agency was very helpful understanding that.

Barry Greene: And the agency was very helpful understanding that while we had a file to package, we had two studies up and running, the Coral Study, which we've announced as positive, and the upcoming Skylark Study, which we plan on announcing mid-year. And again, the strategic discussion said, let's file MDD first, which we've just started the rolling submission, and then file PPD as an additional NDA after that. And what we're hopeful for, although timing's not in our hand, is that with approval of xeraniline for MDD, we then commence a DEA review, which is typically a three-month review.

While we have filed a package we had two studies up and running the Coral study, which we've announced is positive and the upcoming Skylark study, which we plan on announcing mid year.

<unk>.

Again, the strategic discussion said, let's file MDT first which we've just started the rolling submission and then and then file PPD as an additional NDA after that and what we're hopeful for although timing is not in our hand is that with the approval of <unk> for MVD. We then commence.

A deep DEA review, which is typically a three month review and given as you said the priority of you were hopeful in that period that we could get PPD approved and launch both indications at the same time.

Barry Greene: And given, as you said, the priority review, we're hopeful in that period that we could get PPD approved and launch both indications at the same time. You know, if MDD comes first and PPD comes a month or two after, that's fine as well. But that's the goal.

<unk> PBT comes a month or two after that's fine as well, but that's the goal and some time.

Barry Greene: And you know, sometime, you know, after we submit, sometime next year, we hope to get the approval of MDD, and then followed by PPD thereafter. Thanks. Thanks, everyone. Comfort Line of O'Meara Devine from Mizzou, you may be, Great, thanks for taking my question.

After we submit.

Sometime next year, we hope to get the approval of <unk> and then followed by PPD thereafter.

Yeah.

Got it thanks.

Thanks, Ed.

Our next question will come from the line of.

Demand from Mizuho you may begin.

Unknown Speaker: Maybe just one higher level question that we get from investors periodically. And just, obviously, for both Serenalone and 324, you're partnered with Biogen, and there's obviously a lot of transition and changes happening at Biogen, and looks like more to come. So I'm just curious if you can sort of talk about the relationship and sort of on the product level, I guess, sort of the data, obviously, you're doing good progress with the submission and everything along those lines.

Great. Thanks for taking my question, maybe just one higher level question that we get from them.

<unk> periodically and just other equal both standalone and pre tier four you're partnered with Biogen.

Lana.

Transitioning to changes happening at Biogen and let's take more of that come. So I'm. Just curious if you can sort of talk about the relationship and so on the product level I guess is sort of the data obviously doing good progress with the submission and everything along those lines I think seem to be on track, but can you just reassure that and on the product level.

Unknown Speaker: So things seem to be on track. But can you just sort of reassure that on the product level, things are still on track and everything in terms of that coming from your partner? Yeah, Vimil, thank you for that question. Very important question.

Things are still on track in terms of that I can I mean youre seeing from your.

Partner.

Okay. Thank you.

Thank you for that question very important question obviously.

Barry Greene: And obviously, we all saw the press release this morning of Biogen, you know, unfortunate further restructuring given the challenges they've had with Adelhelm and the search for CEO with Michelle's replacement. You know, what I can tell you is, and the other highlight, I think, in the press release is that they're looking at Serenalone as a key growth driver for the company. So that's an important comment from them.

Saw the press release this morning, the Biogen unfortunate further restructuring given the challenges they've had with that'll home in the search for CEO with Michelle's replacement.

What I can tell you is the other highlight I think in the press release is that Theyre looking at <unk> alone as a key growth driver for the company. So that's an important comment from them. It's been consistent that their long range plan is heavily dependent on an <unk> loan, which we and they believe will be very important in the depression landscape. So at a team level we're incredibly.

Barry Greene: It's been consistent that their long-range plan is heavily dependent on Serenalone, which we and they believe will be very important in the depression landscape. So at a team level, we are incredibly well aligned from a CMC perspective, a clinical development perspective, a commercialization perspective. And of course, we're co-co-ing in the United States, and they're responsible for the rest of the world, except for Japan, Korea, and Taiwan.

Well why well aligned from a CMC perspective of clinical development spec of the commercialization.

Perspective and of course, we're coco into the United States and they're responsible for.

For rest of world, except for Japan, Korea, and Taiwan, So things are going incredibly well Michelle has been a wonderful partner.

Barry Greene: So things are going incredibly well. Michelle's been a wonderful partner. You know, I wish them well on their search, and I wish him well in his future endeavors. But things are very strong at the senior level and the team level. And again, you know, that should not be surprising because Serenal is strategically important to Biogen. It's recognized by the board. It's recognized by the entire team, leadership team and community at Biogen. So things are going very well. Okay, thank you. Question comes from the line of Neena.

I wish them well in their search and I wish him well in his future endeavors, but things are very strong at the senior level and the team level and again.

That should not be surprising because the rental is strategically important to biogen is recognized by the board it's recognized by the entire.

Team leadership team and community Biogen, so things are going very well.

Okay. Thank you.

Our next question comes from the line of Neil.

B <unk> garg from Citi you may begin.

Unknown Speaker: Dr. Gard from City, maybe... Hey, guys, thanks for taking my question. I was just wondering if you could share a little bit more about the Skylark final population that was enrolled, if you can share how many patients were ultimately enrolled and any notable, I guess, baseline characteristics or differences versus Robin other than, of those that you already described in regards. Yeah, and you know, so there's not a lot we can say about Skylark until we have the top line results. But Jim, any color to add?

Hey, guys. Thanks for taking my question I was just wondering if you could share a little bit more about the skylark final population that was enrolled if you can share how many patients are ultimately enrolled and any notable I guess baseline characteristics or differences versus Robyn other than.

And you already described.

Thanks.

Yes.

So theres not a lot we can say about skylark until we have the topline results data, but Jim any color to add.

Jim Daugherty: Right. So I think that's right, Barry. I mean, what we can say is the target enrollment was 200 subjects. So as we, as we were able to talk about the results in the study, coming up, we'll be able to talk about the specifics that were enrolled in the study, but the target was 200. Got it.

So I think Thats right Barry I mean, what we can say its target enrollment was 200 subjects. So.

As we as we were able to talk about the results from the study.

Coming up we will we'll be able to talk about the specifics that we're enrolling studies target was 200.

Got it thank you.

Thanks Nina.

Unknown Speaker: Thank you. Thanks, Neena. Question from Sumant Kulkarni, and Kami Parsa, Please visit us at www. KamiParsa.org.

Our next question comes from the line of Simonton.

Kearney from Canaccord you may begin.

Unknown Speaker: Thank you. Good morning, thanks for taking my question. Given the time you have to complete the submission, could you share any latest thoughts you have on how you might be able to target MDD with elevated anxiety as a use case to include in the label? Yeah, Sumant, thanks for the question. So, you know, what we've highlighted is that we've seen effects of seranilone in MDD with or without elevated anxiety. The reason that we're highlighting the elevated anxiety component is we know through the literature, including studies like STAR-D, that when patients present with MDD and have elevated anxiety as a feature of their depressive symptoms, they often are very much underserved by standard of care.

Good morning, Thanks for taking my question given the time you'd have to complete the submission could you shed any latest thoughts you have on how you might be able to target MBT with elevated anxiety is a use case.

In the label.

Yes. Thanks, Thanks for the question so.

Barry Greene: So we think that by highlighting that more from a commercial perspective will help, help potential prescribers see a patient that might have elevated anxiety and reach for xeranilone first. Of course, as we highlighted, there's a number of use cases, I won't repeat, of patient characteristics like the young adult, the elderly, that also with or without elevated anxiety is a piece. You know, whether the data are in or not is too early to tell.

We highlighted is that we've seen effects of surround alone in MTBE.

Without elevated anxiety the reason that we're highlighting the elevating xiety component as we know through the literature, including studies like Star D.

When patients present, with MVD and have elevated anxiety as a feature of the depressive symptoms.

They often are very much underserved by standard of care. So we think that by highlighting that more from a commercial perspective will help.

Help for potential prescribers CF patient that might've elevating side and reached for us around first of course as we highlighted there's a number of use cases that won't repeat.

Ah patient characters like the young adult the elderly that also with or without elevating <unk> piece, whether whether the data are in or not too early to tell I'll remind everybody that in the coral study, we prospectively defined that that group of them to deal with all the anxiety. So we do have a prospective study that that hit very robustly and we will see how.

Barry Greene: I'll remind everybody that in the CORAL study, we prospectively defined that group of MDD with elevated anxiety. So we do have a prospective study that hit very robustly, and we'll see how we can use those data. Thanks. Thanks a lot. Brian Abrahams from RBC, Hi, this is Joe for Brian.

We can use those data.

Thank you.

Thanks Mark.

Our next question comes from Brian Abrahams from RBC capital markets you may begin.

Hi, This is Joe on for Brian . Thanks for taking my question and congrats on the progress and just quickly on 324 and could you help us better understand the segmentation of essential tremor market.

Unknown Speaker: Thank you for taking our question and congrats on the progress. Just quickly on 324, could you help us better understand the segmentation of the essential tremor market? What portion of the patients are currently not well controlled and actually looking for additional efficacy? And are you primarily focused on monotherapy use or are there any potential for a combinational approach? Thank you. Yeah, great question, Joe.

What portion of the patients that are currently not well controlled and actually looking for additional efficacy and then are you primarily focused on monotherapy use or are there any potential for combination of approach. Thank you.

Yes, Great question, Joe Christopher will highlight.

Chris Benecchi: Chris, you want to highlight, you know, the significant essential tremor population and how we're thinking about approaching it? Yeah, so initially, what we can say is that essential tremor is one of the most common movement disorders seen in the US and it's estimated to impact approximately 6.4 million Americans. And that's approximately one in six with essential tremor diagnosed and seeking treatment.

The significant essential tremor population and how we're thinking about approaching it yeah. So initially what we can say is that essential tremor is one of the most common movement disorders seen in the U S.

Estimated to impact approximately $6 40 million Americans and Thats approximately $1 six with the central tremor diagnosed and seeking treatment. So clearly there is unmet need and there's still a gap with respect to our ability to serve all of the patients that are suffering from a central tremor. So as we take a step back when we think about it right now we see it as a sign.

Chris Benecchi: So clearly, there is unmet need and there's still a gap with respect to our ability to serve all of the patients that are suffering from essential tremor. So as we take a step back and we think about it right now, we see it as a sizable opportunity with profound unmet. Page 324 has the opportunity or the potential to be a very important therapy for patients with Ascension. Yeah, I would just add, Joe, that, you know, based upon the data we've seen in kinetic, that, you know, 30 to 40 some percent improvement in tremor amplitude associated with improvement in activities of daily living is critical.

So the opportunity with profound unmet need for which phase three to four has the opportunity or the potential to be a very important therapy for patients with essential tremor.

Chris Benecchi: And when you talk to a patient with essential tremor, that is maybe branded as mild, if they can't lift their spoon to their mouth and feed themselves, that's not so mild. So we think there's a very broad opportunity here for a chronic treatment. People with essential tremor want to be covered at all times, because whether it's trying to button their shirt or eat or text, they don't want those last moments where they can't do that or need to take a drug and wait several hours.

Yes, I would just add.

Joe that.

Based upon the data we've seen in kinetic.

<unk>.

30 to 40 some percent improvement in <unk>.

Tremor amplitude associated with improvement in activities of daily living is critical and when you talk to.

With essential tremor.

That is.

Maybe branded as mild if they can't lift their spoons of their mouth and feed themselves. That's not so miles. So we think there's a very broad opportunity here for a chronic treatment with people with the central Chamber Wanna be covered at all times, because whether it's trying to button their shirt or eat protest. They don't want those last moments, where they can't do that or need to take a drug in <unk>.

Barry Greene: So we're pretty happy with the profile we have. And we'll prove in kinetic two, you know, a dose and frequency for chronic treatment. Got it.

Several hours, so we're pretty happy with the profile, we have and will prove in kinetic too.

Dosing frequency for chronic treatment.

Got it thank you.

Thanks, Joe.

Unknown Speaker: Thank you. Thanks, Joe, line up Tim Little from William Blair Media. Hey guys, this is Lachlan on for Tim.

Our next question will come from the line of Tim <unk> from William Blair.

Yes.

Unknown Speaker: Thanks for taking the question. I had another one similar to Vamil's question on just the collaboration with Biogen. I had a couple of questions on if they've got a new CEO that wanted to take the company in a different direction, what does the sort of collaboration allow for and how would that impact your plans for Surround London 324? Yeah, Laughlin.

Hey, this is lachlan on for Tim Thanks for taking the question I don't want another one similar to Neal's question on just the collaboration with Biogen tried a couple of questions.

Yes.

<unk> got a new CEO .

I wanted to take the company in a different direction.

Does the sort of collaboration allow for and how would that impact your plans for <unk>.

It's around one in three unusual.

Sure.

Barry Greene: Again, so Biogen, as we highlighted, from a Biogen perspective, they highlighted in their press release several different times that one of their key growth drivers going forward is xeranilone. And we certainly agree, it's a major growth driver for them. And for us, we're going to co-code in the United States, but they have the opportunity to launch xeranilone in countries around the world where depression is as big a problem around the world as it is here, particularly post COVID. So it is a very big strategic driver for Biogen.

Yes, I'll, often again biogen as we highlighted from a biogen perspective, they highlighted in their press release several different times that one of their key growth drivers going forward is around alone. We certainly agree it's a major growth driver for them and for US, we're going to Coco in United States, but they have the opportunity to launch.

Or and alone in countries around the world.

Depression as big a problem around the world as it is here, particularly post COVID-19. So it is a very big strategic driver for Biogen I really don't believe that theres a different direction other than what they've done which is continue to partner with us effectively.

Barry Greene: I really don't believe that there's a different direction other than what they've done, which is continue to partner with us effectively, both on the regulatory, the clinical development front, the phase three, four, three and four studies, as well as the commercialization strategy. So things are going incredibly well. We also are partnered with SAGE 324, and they're excited about the opportunity there in essential tremor, which we also think will be another growth driver for them. So, you know, unless there's sort of an M&A move, the partnership with SAGE, with xeranilone 324 are a big part of growth drivers.

Both on the regulatory the clinical development front, the phase III for three and four studies as well as the commercialization strategy.

Things are going.

Incredibly well. We also are partnered with Sage three to four and they are excited about the opportunity there in essential tremor, which we also think will be another growth driver for them. So.

Unless there is sort of an M&A move.

Partnership with Sage was around three to four are a big part of growth drivers.

Got it thanks.

Unknown Speaker: Douglas Goldstein, CFP®, Financial Planner & Investment Advisor, Thanks, Laughlin. And our last question will be from the line of Yasmeen Rahimi from. Hi, guys.

Thanks, a lot.

And our last question will be from the line of <unk> <unk> from Piper Sandler Your line is open.

Okay.

Hi, guys. Thanks again.

Unknown Speaker: Thanks again. So just one last question. For the 50 mg dose group, are you planning to share some of the findings from inability of driving the next morning for patients? And then just any color on that.

Just one last question for the <unk> dose group are you planning to share some of the findings from.

Inability of driving the next morning for patients and then just any color on that thank you.

Hi, Laurent yes.

Barry Greene: Thank you. Hi, Lauren. Yes, we've completed the driving studies. And while it's too early to give specifics, and we haven't really negotiated with the agency, there's likely, as we see with many drugs, including OTC drugs, to be those kind of commentary, you know, don't operate heavy machinery to know the effects of the drug. And a warning like that will not be a problem.

Yes, we've compete we've completed the driving studies and while it's truly too.

Give specifics and we Havent really negotiated with the agency there is likely as we see with many drugs, including OTC drug to be those kind of commentary don't operate heavy machinery to know the effects of the drug in a warning like that will not be a problem.

Perfect. Thanks.

Barry Greene: Perfect, thanks. Barry for Nicole's, Thanks, Victor. And thanks, everyone, again, for joining us this morning to review our first quarter progress. I'm really grateful to the entire SAGE team, our patients, caregivers, and clinical investigators, and all who've dedicated so much to help us advance our mission to become the leader in brain health. Current events have put a spotlight on the need for significant progress in brain health disorders, and it's never been more important to prioritize addressing these disorders, including mental health disorders, as an essential component to overall health and well-being.

And I will now turn the call back over to Barry for any closing remarks.

Barry Greene: At SAGE, we recognize the great unmet need in this space and are working with a sense of urgency to make a difference for patients. In reflecting on our progress achieved during the first quarter, coupled with our expectations for what we hope to achieve in the balance of 2022 and beyond, I'm confident that we're making important progress towards our mission to pioneer solutions to deliver life-changing brain health medicines so every person can thrive. Thanks again, everyone, and have a great day. Goodbye. This concludes today's conference call. Thank you for participating. Thanks for watching!

Thanks, Victor and thanks, everyone again for joining US this morning to review, our first quarter progress I'm really grateful to the entire stage team our patients caregivers and clinical investigators and all who have dedicated so much to help us advance our mission to become the leader in brand health.

Current events have put a spotlight on the need for significant progress in brain health disorders, and it's never been more important to prioritize addressing these disorders, including mental health disorders as in a central components overall health and wellbeing.

Sage, we recognize the great unmet need in this space and are working with a sense of urgency to make a difference for patients and reflecting on our progress achieved during the first quarter, coupled with our expectations for what we hope to achieve in the balance of 2022 and beyond I am confident that we're making important progress towards our mission to pioneer solutions to deliver life changing brain health medicines.

So every person can drive thanks, again, everyone and have a great day.

Goodbye.

This concludes today's conference call. Thank you for participating.

Everyone have a great day.

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