Sage Therapeutics Inc. (SAGE) Q1 2022 Earnings Call Transcript

Sage Therapeutics Inc.  (NASDAQ: SAGE) Q1 2022 earnings call dated May. 03, 2022

Corporate Participants:

Helen Rubinstein — Investor Relations

Barry Greene — Chief Executive Officer

Jim Doherty — Chief Development Officer

Kimi Iguchi — Chief Financial Officer

Chris Benecchi — Chief Commercial Officer

Analysts:

Laura Chico — Wedbush — Analyst

Unidentified Participant — — Analyst

Tiffany Sun — JPMorgan — Analyst

Ritu Baral — Cowen — Analyst

Yatin Suneja — Guggenheim — Analyst

Evan Hua — BMO Capital Markets — Analyst

Vamil Divan — Mizuho — Analyst

Neena Bitritto-Garg — Citi — Analyst

Sumant Kulkarni — Canaccord — Analyst

Lachlan Hanbury-Brown — William Blair — Analyst

Yasmeen Rahimi — Piper Sandler — Analyst

Presentation:

Operator

Good morning. Welcome to Sage Therapeutics’ First Quarter 2022 Financial Results Conference Call. Currently, all participants are in a listen-only mode. This call is being webcast live on the Investors [Technical Issues] This call is the property of Sage Therapeutics and recording reduction or transmission of this call without the expressed written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded.

I would now like to introduce Helen Rubinstein, Investor Relations at Sage.

Helen Rubinstein — Investor Relations

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.

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. Please consult the risk factors discussed in today’s press release and in our SEC filings for additional details.

We will begin the call with prepared remarks by 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 Doherty, our Chief Development Officer who will review recent progress and development activities across our programs; and Kimi Iguchi, 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.

Barry Greene — Chief Executive Officer

Thanks Helen and thank you everyone for joining us this morning. 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. The severity and prevalence of simply facing our nation require all of us to strengthen our response.

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 medicines. Mental Health Awareness Month provides an important reminder of the great unmet need in this area. 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 PPD disorders where advancement has lagged other critical disease areas. With little innovation in the last 60 years, the profile of treatment remains unchanged despite 35 approved treatments in the last 30 years. 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 with current antidepressants, it often takes six to eight weeks if ever for patients to experience benefits from treatment. Tolerability is also frequently an issue. Current antidepressants often cause stigmatizing side effects like sexual dysfunction and weight gain, which can be associated with patient non-adherence.

Further, the prevalence and impact of depression continued to increase with an estimated three to fourfold 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.

In addition an estimated one in eight 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. That’s why we believe there is a significant opportunity to advance the standard-of-care for treating MDD and PPD with zuranolone if approved.

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

We’ll provide the next update when we complete the submission. In addition, we anticipate making an associated NDA filing for zuranolone in PPD in early 2023, pending results from our SKYLARK study, which we continue to expect mid-2022. Jim will provide more details regarding the SKYLARK study and our overall NDA submission plan.

We believe that, the totality of the data that we plan to submit to the FDA from data generated in multiple studies evaluating zuranolone in PPD and MDD patients supports the potential of zuranolone to make a difference for patients. 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 zuranolone has the potential to fill the unmet need and serve both people with MDD and PPD and advance the standard of care. Such advancements will require partnership and engagement with all stakeholders, patients health care professionals, payers, patient advocate groups and policymakers. 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 zuranolone to help those living with MDD and PPD.

Our goal, if zuranolone is approved will be to execute a fit-for-purpose launch that prioritizes deep stakeholder insights driven by data analytics and monitoring that we believe will enable us to strategically deploy our resources across all channels at the right scale.

The targeting agents 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 zuranolone.

From our stakeholder interactions, we know that, there are many types of people with MDD that could potentially benefit from a treatment like zuranolone. They include treatment-naive young adults such as college students, who have an acute stressor that triggers depressive symptoms that derail their lives.

People are receiving antidepressant treatment but still suffering. Those with breakthrough symptoms were in 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 suffice.

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 symptoms.

And when treated with antidepressants this patient group experiences poor depression treatment outcomes and lower remission rates. We’ve learned that from a clinician’s perspective these patients are incredibly challenging to treat. As 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, zuranolone’s mechanism of action is distinct from current antidepressants. Based upon data seen in our MDD studies to-date, which have included both patients with elevating anxiety as a symptom of their depression and those without symptoms of anxiety, including data on improvements in quality of life, we believe zuranolone maybe well suited to address a clear unmet need for people with MDD, regardless of their baseline anxiety symptoms.

It’s also important to note that, for women struggling with PPD many present with anxiety as an important feature of their disease. I’m confident in the profile, we’ve seen with zuranolone 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 zuranolone, 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 as a potential treatment for patients suffering from essential tremor and other neurological disorders.

Across both franchises, we have six ongoing and planned Phase II studies in the neuropsych franchise with SAGE-718. These include DIMENSION and SURVEYOR both for patients with Huntington disease cognitive impairment. PRECEDENT for patients with Parkinson’s with mild impairment and a Phase II in patients with mild cognitive impairment and mild dementia due to Alzheimer’s disease.

In the neurology franchise these include KINETIC two 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 Pollack to Sage as Senior Vice President of Medical Affairs. Mark brings significant experience in scientific research and medical practice across industry and academia to organization. In his role at Sage, he will lead our Global Medical Affairs’ efforts across our programs. Scientific exchange, KOL insights, publications, presentations at scientific congresses and plans for Phase 3b/4 studies are critical aspects of our Medical Affairs strategy.

I’m confident that Mark’s contributions across Sage will help to further support our relationships with the medical community and patient advocacy in support of our goal to become the leader in brain health. And reflecting on our progress during the first quarter and 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 medicine.

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 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 Doherty — Chief Development Officer

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 zuranolone in collaboration with Biogen.

With the CORAL study data shared earlier this year, we now have six positive clinical trials with zuranolone in MDD and PPD across the LANDSCAPE and NEST programs and the Shionogi Phase two trial in MDD. The clinical profile we have seen to date includes; one, a rapid and sustained reduction in depressive symptoms; two, a well-tolerated safety profile; three, improvements in quality of life and overall health across domains of feeling, functioning and well-being that were reported by patients and continued post-treatment in the studies where we collected these data, or 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 MDD and PPD that may provide optionality to health care providers and patients if zuranolone 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 zuranolone in PPD in early 2023. The SKYLARK study forms an important component for our planned NDA filing package for zuranolone in PPD. 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 ROBIN study was a Phase three study evaluating the effects of zuranolone 30-milligram on depressive symptoms in approximately 151 adult women diagnosed with PPD. In the ROBIN study, we saw a statistically significant reduction in depressive symptoms in the zuranolone arm compared to placebo at day 15, the primary endpoint as well as day three, day eight, day 21 and day 45. Additionally, zuranolone 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 three clinical trial evaluating a two-week course of zuranolone in women with PPD with an additional short-term follow-up. Notably the SKYLARK study differs from the ROBIN study in three key areas. First the dose, the SKYLARK study is evaluating a 50-milligram dose of zuranolone, whereas, zuranolone 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.

We believe that the trial’s primary endpoint, the change from baseline as measured by the HAM-D 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 zuranolone, 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 zuranolone that would be meaningful in 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 zuranolone 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 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.

Most importantly, we believe the SKYLARK study can positively contribute to the body of evidence that we have assembled for zuranolone in PPD. So, that if zuranolone is approved, moms with PPD and their doctors can be informed and empowered in assessing zuranolone as a treatment option for PPD. We look forward to updating you on the top line results of the SKYLARK study midyear and providing more detail on our planned associated NDA filing for zuranolone in PPD.

I’m also excited to share that we’ve completed our clinical pharmacology studies with zuranolone, including a Human Abuse Potential or HAP study. In the HAP study, doses of zuranolone representative of the planned target range of 30 to 60 milligrams were significantly less preferred than alprazolam at either 1.5 or three milligrams by recreational depressant users the standard population for this type of trial. We plan to present the data from this study at the College on Problems of Drug 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 zuranolone 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 zuranolone in the future.

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.

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. Starting with SAGE-718 in HD, we are currently enrolling the DIMENSION study, a placebo-controlled Phase II study of SAGE-718 in HD cognitive impairment. Additionally, we recently announced that we have initiated the SURVEYOR study, our second Phase II 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. 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 potential paths 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 two 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.

Finally, we are advancing our efforts to evaluate SAGE-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. We are on track with our plans to initiate a placebo-controlled Phase two study with SAGE-718 in patients with mild cognitive impairment and mild dementia due to AD in late 2022.

I would also like the 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 & 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 two 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.

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.

As a reminder SAGE-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 two dose-ranging study evaluating SAGE-324. KINETIC two is designed to optimize the dose and frequency of SAGE-324 in ET. We also shared the study design for our planned Phase two long-term open-label safety study with SAGE-324 in ET 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 multiyear study with the incidence of treatment-emergent adverse events as the primary end point. 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 a review of our financials. Kimi?

Kimi Iguchi — Chief Financial Officer

Thanks, Jim. Our financial results for the first quarter of 2022 are detailed in our press release issued this morning. So I’ll only 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 and with upcoming milestones, I’m confident that our progress during the first quarter and the period since then moved us closer to our goal of delivering life-changing brain health medicines 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.

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 zuranolone, including spending on SAGE-324 and our wholly owned pipeline which includes SAGE-718.

As a reminder we have six planned and ongoing Phase two studies across our neurology and neuropsychiatry franchises. 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. The increase was 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 License Agreement. Recall the, collaboration includes a 50-50 cost sharing in the United States for zuranolone and SAGE-324.

The savings from the cost sharing for zuranolone and SAGE-324 enables us to use our cash on hand to continue to invest in advancing our wholly owned pipeline in a smart and disciplined way.

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 2022. 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?

Helen Rubinstein — Investor Relations

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?

Questions and Answers:

Operator

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

Laura Chico — Wedbush — Analyst

Hey. 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 for a depressive episode and I realize that this probably facilitates enrollment. But from a scientific perspective, how does this affect the heterogeneity of your enrollment population? Thank you.

Barry Greene — Chief Executive Officer

Hey, Laura thanks for the question. I really appreciate it. 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 of notable changes, the 50-milligram change the bigger end which is important.

And as you highlighted, seeing women with depression out to 12 months versus just six months they really aren’t that different. And Jim do you want to just highlight that rationale?

Jim Doherty — Chief Development Officer

Yeah. Barry absolutely. And yeah Laura, as you mentioned it certainly gives us a wider net for patients who enroll in the study. But importantly, the case that, women with PPD have on-set of PPD, sometime between the third trimester, or the first six months, but the symptoms persist and we’ve known that for some time.

So in our estimation it really isn’t changing the population all that much. And it just gives a wider set of women the opportunity to participate in the trial.

Laura Chico — Wedbush — Analyst

Thanks guys.

Jim Doherty — Chief Development Officer

Thanks, Laura.

Operator

Our next question comes from the line of Yasmeen Rahimi from Piper Sandler. Your line is open.

Unidentified Participant — — Analyst

This is Lauren [Phonetic] on for Yasmeen. Thanks for taking my question. So looking across the landscape studies when you look into the safety profile for zuranolone what rates of somnolence were 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 somnolence and sedation in patients with and without anxiety? Thank you.

Barry Greene — Chief Executive Officer

Yes Lauren, thanks for the question. Please say hi to Yas, for us. So if we step back what we’re seeing is an incredibly broad therapeutic index with zuranolone. 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 sleep aids. So having some degree of somnolence is actually a benefit to these patients. Jim, do you want to talk about rates?

Jim Doherty — Chief Development Officer

Yes, absolutely Barry. And of course, now that we have the entire landscape program assembled of course we have the ability to measure somnolence and sedation in the efficacy trials which we spend 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.

And so of course as we talked about before rates all are dose dependent. But I do think probably the range quote would be somewhere in the teens for somnolence, depending on the trial, low teens to high teens in other trials depending on specific trials and specific dose. And that we think is consistent with the mechanism of action and consistence and compares quite well with the rates of safety in somnolence associated with current standard of care in antidepressants.

Barry Greene — Chief Executive Officer

And I will highlight to keep in mind that we’re not seeing the stigmatizing side effects often seen with antidepressants things like weight gain, sexual dysfunction. And as we report out with CORAL you see a significant amount of GI upset with antidepressants too. And we don’t have those side effects which often lead to compliance challenges.

Unidentified Participant — — Analyst

Perfect. Thank you.

Operator

Our next question will come from the line of Jay Olson from Oppenheimer. Your line is open.

Unidentified Participant — — Analyst

Congrats on the process — the progress. This is Matt on for Jay. So. we were just curious about any physician feedback that you received at AAN on SAGE-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.

Barry Greene — Chief Executive Officer

Hey Matt, thanks. Appreciate it. 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 Koenig presented the data both into slide presentation and poster session. It was probably the most crowded presentation and one of the most exciting things presented at AAN. His poster was packed and the rooms were mobbed with presentations.

I can say that 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 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. Chris you were there. Do you want to talk a little bit more about what you heard personally?

Chris Benecchi — Chief Commercial Officer

Yes. So personally, there was a great deal of excitement as Barry mentioned. I think in standing back and reflecting on it 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 no 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. These are patients who are really suffering from the effects associated with cognitive impairment and a loss of independence. And 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 those back.

Unidentified Participant — — Analyst

Got it. Thank you so much.

Barry Greene — Chief Executive Officer

Thanks Matt.

Operator

Our next question comes from the line of Cory Kasimov from JPMorgan. Your line is open.

Tiffany Sun — JPMorgan — Analyst

Hi, guys. This is Tiffany, on for Cory. 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? Thank you.

Barry Greene — Chief Executive Officer

Hi, 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 trials. So look the trials 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, do you want to talk about the different designs and how we size them?

Jim Doherty — Chief Development Officer

Absolutely, Barry. Yes. So the PRECEDENT study represents what will be the first placebo-controlled study or 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 serial 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 SAGE-718 providing benefit to this patient group, but also the opportunity to really hone the safety — sorry the study design for the PRECEDENT study. So PRECEDENT study unlike the earlier study is a 42-day duration dosing. So the dosing period is longer in 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.

Tiffany Sun — JPMorgan — Analyst

Great. Thanks.

Barry Greene — Chief Executive Officer

Thanks, Tiffany.

Operator

Our next question will come from the line of Ritu Baral from Cowen. You may begin.

Ritu Baral — Cowen — Analyst

Good morning, everyone. Thanks for taking my question. I wanted to ask about the rolling submission and what you’re going to be asking for. I guess one can you — Barry can you go through just the outstanding items before you guys can submit the clinical module and what’s the most important gating steps are to that? And second, just given you’re going after sort of a broad population you outlined your 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? And what sort of benzo black boxes do you think will translate especially that most recent one? Thanks.

Barry Greene — Chief Executive Officer

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 such we’re very excited to have started the rolling submission with the nonclinical 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 compiling the studies going through the QA process and making sure we have the highest quality submission. We will let everybody know when we finished, filing the NDA in the second half of the year and then we’ll communicate further when the NDA is accepted. So this will be the communication.

But I can say that all of the section — all of the modules are in very good shape. 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 what we’re asking for, it’s too early to talk about label specifics or any kind of warnings but what we are seeing and studying is we have a drug here zuranolone for the treatment of MDD and PPD with or without elevated anxiety.

So that’s the kind of discussions, we envision in having with the agency. In terms of warnings again, too early to talk about specifics. We’ll have some of the typical things in there don’t operate heavy machinery until you know how the drug works things like that. But we’re not sure if we’ll have zuranolone-specific issues where warnings were class-like warnings, it’s too early to tell. We’re certainly going to accept certain warnings that are classic, like I just highlighted and maybe push back in some others because if we’re not seeing certain effects, we don’t think we should have warnings there.

Ritu Baral — Cowen — Analyst

Got it. Great. Thanks I’ll get back in the queue.

Barry Greene — Chief Executive Officer

Thanks, Ritu.

Operator

Our next question comes from the line of Salveen Richter from Goldman Sachs. You may begin.

Unidentified Participant — — Analyst

This is Tommy [Phonetic] on for Salveen. 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 less frequent dosing? Thanks.

This is Tommy [Phonetic] on for Salveen. 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 less frequent dosing? Thanks.

Barry Greene — Chief Executive Officer

Yes, Tommy, great question. Appreciate the attention on SAGE-718. So as Jim highlighted, we continue to learn and serial derisk the studies. We’re 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 as an 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 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 dose disruption. So right now, we believe it’s a chronic drug. Jim, anything to add?

Jim Doherty — Chief Development Officer

Just, Barry, that part of what the status studies is designed to do, is to give us further information about how the drug is performing with repeat dosing. As Barry said, our current assumptions are chronic dosing and — but we have enough diversity amongst clinical trials that 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, seven to 14 days. But as we go to the next round of studies, we’ll have longer-duration dosing and really get more detail into the specific questions about how 718 can be delivered.

Unidentified Participant — — Analyst

Thank you.

Barry Greene — Chief Executive Officer

Thanks, Tommy.

Operator

Our next question will come from the line of Akash Tewari from Jefferies. You may begin.

Unidentified Participant — — Analyst

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

Do you set a reserve for potential callback from the payers, if patient use more courses of zuranolone in one year? In addition when you have conversations with payers do they mention any potential requirement for product authorizations or requirement of patients to try generic antidepressants first and then does VBA actually lower the payers’ requirement for prescribing zuranolone? Thank you.

Barry Greene — Chief Executive Officer

Yeah. Thanks, Leo. Let me try to unpack a couple of those questions 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 patient deserves zuranolone, gets zuranolone without step-throughs and without prior auths. It’s very important, given the features of zuranolone that if someone is depressed they get zuranolone quickly, so they can get better in two or three days. 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, undertreated 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 ask with payers is that, again, if a script comes in, it gets filled without a lot of hurdles.

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 zuranolone. We can protect them if it goes over that.

They might be concerned that their patient population, instead of needing one to two, two-week course in the course of the year, 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 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.

Kimi Iguchi — Chief Financial Officer

Great. Sure. Thanks. 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 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 zuranolone 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 and then we would reduce it by the collaboration-related SG&A expenses. So that would be in the revenue line. 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 will look. So I’ll turn it over to Chris now.

Chris Benecchi — Chief Commercial Officer

Yeah, sure. And I’ll take it Barry. Leo, thanks for the question. 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 coming in at the planned level. 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.

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 other neurological conditions. 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 zuranolone, 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 then often are determinants of adherence. This is a highly attractive therapy for payers and it has been really positive and productive conversations that we’ve initially had. We look forward to continuing on with those.

Unidentified Participant — — Analyst

Thank you very much.

Barry Greene — Chief Executive Officer

Thanks, Leo.

Operator

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

Unidentified Participant — — Analyst

Hi. This is James [Phonetic] on for Paul. 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 and in SHORELINE there is restrictions around, when a patient can be redosed 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 redosing? And if there are how that may play out commercially? Thanks.

Barry Greene — Chief Executive Officer

Yeah. James, thank you for the question on the regulatory pathway. And again, we were 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 in SHORELINE 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 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 the year only required one, two week course of treatment and then 80% only required one or two, two week courses of treatment. So in the real world, we think that the majority of patients treated will require only one or two week courses. And of course I explained with Leo’s question part of the value-based agreements we’ll be providing protections over a couple two-week course 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. In fact of the adverse event numerically actually goes down with each and every course. So we’ve got a good argument to allow retreatment when allowed, 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 treatment, there’s no reason why they couldn’t get it from a data perspective.

Now, going to an extreme, if the agency were to restrict the retreatment to a time frame or only to two, two-week courses 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 courses of treatment for the majority of patients.

Operator

And our next question will come from the line of Marc Goodman from SVB Securities. You may begin.

Unidentified Participant — — Analyst

Thanks for taking my question. This is Rudy on the line for Marc. Congrats on the initiation of the rolling NDA submission. So I have a question regarding the Phase two SURVEYOR study of SAGE-718. So it seems like you have both Huntington’s disease and healthy subjects in the study. Can you provide more color on the trial design? And what is the rationale of adding the healthy participants as a comparator arm? Thanks.

Barry Greene — Chief Executive Officer

Yes, Rudy again and thank you for the congratulatory note. So as we’re thinking about Huntington disease and starting with Huntington’s as everyone is 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 will give us significant energy to approach regulators for the fastest way to get the drug to market. So as an overall package that’s how we’re thinking about the study the numerical values and DIMENSION coupled with the real world evidence in SURVEYOR. So that’s the overall strategy and thought process. But Jim do you want to talk more about SURVEYOR?

Jim Doherty — Chief Development Officer

Yes, absolutely, Barry. And 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 composite score from the Huntington’s disease cognitive assessment battery, 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 an addition to that a healthy participant group. So there are three arms in SURVEYOR. So the subjects from the HD group will be randomized either to say 718 or to placebo. So we get that placebo-controlled 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 SAGE-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. Thanks. That’s very helpful. Thanks, Rudy.

Operator

Our next question will come from the line of Yatin Suneja from Guggenheim. You may begin.

Yatin Suneja — Guggenheim — Analyst

Hello. Hey, guys. Thank you for taking my question. Question on SKYLARK. Can you just talk about like the expectation what feedback have you received from the KOLs in terms of the efficacy is that different for PPD versus MDD? Just trying to get a sense of the delta that we should be expecting on the MDD. And then how would the redosing work in PPD which you generally defined as little bit of a temporary depression? Will those women be eligible to get only one dose, or could they get additional dose? Thanks.

Barry Greene — Chief Executive Officer

Yes. Yatin, 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 midyear. We’ve — 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 anxiety depression. So we believe that with a positive SKYLARK study and to be clear stat-sig at day 15 without any surprising side effect is what we’re looking for a submittable study for PPD.

In terms of redosing that will really be up to a healthcare provider and the patient. As you said what’s generally believed is that the depressive episode is caused by pregnancy or a childbirth. And that what we’ve seen is that most moms when given either ZULRESSO which we have commercially or zuranolone 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 but more from an MDD diagnosis.

Yatin Suneja — Guggenheim — Analyst

Thank you.

Operator

Thank you. Our next question will come from the line of Ami Fadia from Needham. You may begin.

Unidentified Participant — — Analyst

Hello, guys. Thank you for taking the questions. This is Amin [Phonetic] for Ami. 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 wonder if you engage in any discussions that were — the payers were kind of concerned about the priority that you prefer to have compared to what they have in mind is usually the generics than the approved drugs — with the recent approved drugs. If you can elaborate on that that would be great.

Barry Greene — Chief Executive Officer

Yeah, Amin, thanks for the question. So again, within the context of proactive value-based agreements the overall view, 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 zuranolone 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 word they use is patient’s cycle through many drugs. It’s a problem for them.

Even if it’s going from one cheap drug to another having patient population 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. And it’s been well documented that the depressed population, for example, has a higher prevalence of getting COVID or being hospitalized.

All that cost payer. So what we’re hearing from them is, if under the context of value-based agreements so we’re being fair to them they’ll be fair back, they’re actually seeing an agreement that if a healthcare provider writes a script for zuranolone, they have filled the script. And what we’re trying to do, to the extent we can as we’re trying to avoid prior auth, we’re trying to avoid step-throughs, because that’s the wrong thing to do for patients.

Unidentified Participant — — Analyst

Thank you. That is very helpful.

Operator

Our next question will come from the line of Gary Nachman from BMO Capital Markets. You may begin.

Evan Hua — BMO Capital Markets — Analyst

Hi. Thanks for taking our question. This is Evan Hua on for Gary Nachman. 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?

Barry Greene — Chief Executive Officer

Yeah. Evan thanks for the question. So, I can give you generalities and we were very much aided by our strategic discussion with the agency in the fall of last year. Just to remind everybody, we had highlighted that, when we started the LANDSCAPE and NEST 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. And the agency was very helpful understanding that while we had to file the 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 midyear.

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 is not in our hand is that with approval of zuranolone for MDD, we then commence a DEA review, which is typically a three-month review.

And given as you said the prior review, we’re hopeful in that period that we could get PPD approved and launch both indications at the same time. If MDD comes first and PPD comes a month or two after, that’s fine as well. But that’s the goal. And sometime — after we submit, sometime next year we hope to get the approval of MDD and then followed by PPD thereafter.

Evan Hua — BMO Capital Markets — Analyst

Thanks.

Barry Greene — Chief Executive Officer

Thanks, Evan.

Operator

Our next question will come from the line of Vamil Divan from Mizuho. You may begin.

Vamil Divan — Mizuho — Analyst

Great. Thanks for taking my question. Maybe just one higher level question that we get from investors periodically, and just, obviously for both zuranolone and 324 you’re partnered with Biogen and they want to 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 is sort of the data obviously you’re doing good progress with the submission everything along those lines I think seem to be on track. But can you just sort of reassure that on the product level, things are still on track in terms of that — you’re seeing from your partner would be helpful. Thank you.

Barry Greene — Chief Executive Officer

Yes, Vamil, thank you for that question. Very important question. Yes, obviously, we all saw the press release this morning of Biogen unfortunate further restructuring given the challenges they’ve had with ADUHELM and the search for CEO with Michel’s replacement.

What I can tell you is and the other highlight I think in the press release is that they’re looking at zuranolone as a key growth driver for the company. So, that’s an important comment from them and it’s been consistent that their long-range plan is heavily depending on zuranolone 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 prospective, a commercialization perspective. And of course, we’re co-co in the United States and they’re responsible for rest of world except for Japan, Korea, and Taiwan. So, things are going incredibly well.

Michel has been a wonderful partner. 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 zuranolone 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.

Vamil Divan — Mizuho — Analyst

Okay. Thank you.

Operator

Our next question will come from the line of Neena Bitritto-Garg from Citi. You may begin.

Neena Bitritto-Garg — Citi — Analyst

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 kind of those that you already described in regards to the study design? Thanks.

Barry Greene — Chief Executive Officer

Yes, Neena. So, there’s not a lot we can say about SKYLARK until we have the topline results to prevent the data. But Jim any color to add?

Jim Doherty — Chief Development Officer

Right. So, I think that’s right Barry. I mean what we can say is the target enrollment was 200 subjects. So, as we are 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.

Neena Bitritto-Garg — Citi — Analyst

Got it. Thank you.

Barry Greene — Chief Executive Officer

Thanks Neena.

Operator

Our next question will come from the line of Sumant Kulkarni from Canaccord. You may begin.

Sumant Kulkarni — Canaccord — Analyst

Good morning. Thanks for taking my questions. 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?

Barry Greene — Chief Executive Officer

Yes, Sumant, thanks for the question. So, what we’ve highlighted is that we’ve seen effects of zuranolone 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. So, we think that by highlighting that more from a commercial perspective will help potential prescribers to see a patient that might have elevated anxiety and reach for zuranolone first.

Of course, as we highlighted there’s a number of use cases I won’t repeat of patient characters like the young adult, the elderly that also with or without elevating anxiety as a piece. Whether the data are in or not, it’s too early to tell, I’ll remind everybody that in the CORAL study, we prospectively defined that group of MDD with elevated anxiety. We do have a prospective study that hit very robustly. And we’ll see how we can use those data.

Sumant Kulkarni — Canaccord — Analyst

Thank you.

Barry Greene — Chief Executive Officer

Thanks, Sumant.

Operator

Our next question will come from Brian Abrahams from RBC Capital Markets. You may begin.

Unidentified Participant — — Analyst

This is Joe [Phonetic] on for Brian. Thanks for taking my question and congrats on the progress. Just quickly on 324, could you help us better understand the segmentation of this initial 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.

Barry Greene — Chief Executive Officer

Yes. Great question, Joe. Chris, do you want to highlight the significant essential tremor population and how we’re thinking about approaching it?

Chris Benecchi — Chief Commercial Officer

Yes. So initially what we can say is that essential tremor is one of the most common movement disorders seen in the U.S. 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. So, clearly, there is unmet need, and there’s still a gap with respect to our ability to serve all 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 need for which SAGE-324 has the opportunity or the potential to be a very important therapy for patients with essential tremor.

Barry Greene — Chief Executive Officer

Yes. And I would just add, Joe, that based upon the data we’ve seen in KINETIC that 30 to 40 some percent improvement in tremor amplitude associated with improvement in activities of daily living is critical. 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 lapsed moments where they can’t do that or need to take a drug and wait several hours. So we’re pretty happy with the profile we have and we’ll prove in KINETIC two dose and frequency for chronic treatment.

Unidentified Participant — — Analyst

Got it. Thank you.

Barry Greene — Chief Executive Officer

Thanks, Joe.

Operator

Our next question will come from the line of Tim Lugo from William Blair. You may begin.

Lachlan Hanbury-Brown — William Blair — Analyst

Hey, guys. This is Lachlan on for Tim. 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 got a new CEO that they want to just take the company in a different direction what does the sort of collaboration allow for? And how would that impact your plans for zuranolone and 324?

Barry Greene — Chief Executive Officer

Yes, Lachlan. 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 zuranolone. And we certainly agree, it’s a major growth driver for them and for us. We’re going to co-co in the United States, but they have the opportunity to launch zuranolone in countries around the world, where depression as big a problem around the world as it is here particularly post COVID.

So it is a very big strategic driver for Biogen. 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 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, unless there’s sort of an M&A move, the partnership with Sage with zuranolone and 324 are a big part of growth drivers.

Lachlan Hanbury-Brown — William Blair — Analyst

Got it. Thanks.

Barry Greene — Chief Executive Officer

Welcome.

Operator

And our last question will be from the line of Yasmeen Rahimi from Piper Sandler. Your line is open.

Yasmeen Rahimi — Piper Sandler — Analyst

Hi guys. 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? Thank you.

Barry Greene — Chief Executive Officer

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 that don’t operate heavy machinery as you know the effects of the drug. And a warning like that will not be a problem.

Yasmeen Rahimi — Piper Sandler — Analyst

Perfect. Thanks.

Operator

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

Barry Greene — Chief Executive Officer

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.

At Sage, we recognize the great unmet need in the 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’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.

Kimi Iguchi — Chief Financial Officer

Goodbye.