Sage Therapeutics, Inc.

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 made webcast live on the investors' website at sagerx.com. Call is the property of Sage Therapeutics and recording, reproduction, or transmission of this call without the express written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Helen Rubenstein, Investor Relations at Sage.

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 Green, 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 Kimi Iguchi, our Chief Financial Officer, who will review the financial results in the quarter. We will be joined for Q&A by Chris Bonecki, our Chief Commercial Officer. With that, I'll now turn the call over to Barry.

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 symptoms 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 medicine. 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 treatments 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, current antidepressants that often take 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 continue 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. 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's a significant opportunity to advance the standard of care for treating MDD and PPD with Zoranilone, if approved. To this end, yesterday, we and our collaborator Biogen announced a very exciting step towards bringing Zoranilone to market. we began our rolling NDA submission to the FDA for Zoranilone 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 Zoranilone 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 SCAR-like 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 Zoranolone in PPD and MDD patients supports the potential of Zoranolone 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 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 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 Zoranolone to help those living with MDD and PPD. Our goal, if Zorano is 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 scale. 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 xeraniline. From our stakeholder interactions, we know that there are many types of people with MDD who could potentially benefit from a treatment like xeraniline. 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 an antidepressant treatment but still suffering. Those with breakthrough symptoms or an 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 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, Zoranilone's mechanism of action is distinct from current antidepressants. Based upon data seen in our MBD 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 Zoranilone 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 struggling with PPD, many present with anxiety as an important feature of their disease. I'm confident in the profile we've seen with Zoranil and 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, and the differentiated tolerability profile to date, and look forward to sharing more on this program throughout the rest of the year. Now, beyond Zoradalom, 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 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 two in patients with mild cognitive impairment and mild dementia due to Alzheimer's disease. In the neurology franchise, these include panic 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, Medical Affairs. 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 programs. Scientific exchange, KO insights, publications, presentations at scientific congresses, and plans for phase 3B4 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 advocates in support of our goal to become the leader in brain health. In 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 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? 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 choral study data shared earlier this year, we now have six positive clinical trials with Zoranilone in MDD and PPD across the landscape and nest programs and the Shianogi Phase II 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 healthcare providers and patients if Zoran Loan 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 MDA submission for Zoran Loan in PPD in early 2023. The Skylark study forms an important component for our planned NDA filing package for Zoranilone and PPD. The design of the Skylark study is similar to the Robbins study, where we saw positive results in moms with PPD. As a reminder, the Robbins study was a Phase III study evaluating the effects of Zoranilone 30 mg 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 Zoranilone R compared to placebo at day 15, the primary endpoint, as well as day 3, day 8, day 21, and day 45. Additionally, Zoranilone 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 a two-week course of Zoranilone 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 Zoranilone, whereas Zoranilone 30 milligrams was used in the Robin study. Second, the Skylark study is larger than the Robbins 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 HamD 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 Zoranilone 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 Zoranlin 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 of day 15 in the Skylark study, along with the Robin study and safety data from the entire Zoranlin program, would support the associated MDA 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 Zoranlin and PPD, so that if Zoranlin is improved, moms with PPD and their doctors can be informed and empowered in assessing Zoranlin 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 Zoranlin and PPD. I'm also excited to share that we've completed our clinical pharmacology studies with Zaranloan, including a human abuse potential, or HAP, study. In the HAP study, doses of Zaranloan 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. 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 Zoradalyn, 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 Zoranilin in the future. Now I'd like to discuss the progress in our neuropsychiatric franchise led by SAGE718, 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, SAGE718 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 SAGE718 in HD, we are also evaluating its treatment potential for patients with mild cognitive impairment due to Parkinson's disease, or PDE. 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 two study of SAGE 718 in HD cognitive impairment. Additionally, we recently announced that we have initiated the SURVEYER study, our second phase two 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've 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. 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 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. 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 SAGE324, 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, SAGE324 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 2b Kinetic 2 dose-ranging study evaluating Sage 324. Kinetic 2 is designed to optimize the dose and frequency of Sage 324 in ET. We also shared the study design for our planned Phase 2 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 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 a review of our financials. Kimi?