Sage Therapeutics, Inc.

Good morning. Welcome to Sage Therapeutics fourth quarter and full year 2021 financial results conference call. Currently, all participants are in listen-only mode. This call is being webcast live on the investor and media section of Sage's website at sagerx.com. This call is the property of Sage Therapeutics and recordings, reproduction, or transmissions of this call without the written... Consent of Sage Therapeutic is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Helen Rubenstein, Director of Investor Relations at Sage.

Good morning, and thank you for joining Sage Therapeutic's fourth quarter and full year 2021 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 from the previous quarter and full year 2021. We will also be joined by Jim Doherty, our Chief Development Officer, who will review recent development progress across our programs, and Kimi Yaguchi, our Chief Financial Officer, who will review the financial results from the quarter. Chris Bonecki, our Chief Commercial Officer, will join for Q&A. With that, I'll now turn the call over to Barry.

Thanks, Helen, and thank you, everyone, for joining us this morning. Before I begin, I want to take a moment to acknowledge the major events happening on the world stage this morning. We're watching along with the rest of the world, and our thoughts and prayers are with all those affected. Rest assured, we'll be focused on doing what we can, developing innovative medicines for brain health. And now let me turn back to our quarterly call. 2021 was an important year for Sage, and going into 2022, we're well-positioned to advance our mission to pioneer solutions to deliver life-changing brain health medicines so every person can thrive. By leveraging our significant expertise in brain circuitry with demonstrated leadership in GABA-A and NMDA receptor pathways, we've developed a robust pipeline of programs, including six new chemical entity development candidates across 11 or more possible indications. We believe that with this novel pipeline, we have the potential to help the millions of people suffering from the unmet need in brain health disorders, and we look forward to helping as many as we can in the years to come. I'd like to begin by providing some context on MDD and PPD. Families living with depression have not been well served. Largely stigmatized, depression is the dark shadow of human illness. Current treatments are just not working well enough, with little innovation in the last 60 years. The profile of treatments remain unchanged despite 35 approved treatments in the last 30 years. Prevalence and impact continue to worsen. with a three- to four-fold increase in people experiencing symptoms of depression since the start of the COVID-19 pandemic, and an estimated one in eight women with a recent live birth experiencing postpartum depression. The economic implications are as dire as the health implications. In 2020, economists estimated that depression and mood disorders cost the U.S. alone over $784 billion. Change is needed. We need medicines that work faster, last longer, are well-tolerated, and look beyond depression as a lifelong chronic illness. The current treatment approach results in a trier and error pattern. Delays in resolving MDD symptoms as seen with current antidepressants are often associated with more severe depression, increased relapse rates, and worse long-term clinical outcomes. We believe patients deserve better. As a society, we can do better. Innovative thinking leads to valuable advancements that benefit society. The riskiest thing we can do for people is to maintain the status quo and believe that what we have is good enough. The data are clear. For the nearly 7 million people diagnosed with MDD and prescribed an antidepressant each year, the average course of therapy is only seven weeks. And 80% of patients change treatments once or twice within the first year. And among those that have changed treatments, 50% change within the first month. patients clearly need more from their therapy. That's why we believe there's a significant opportunity for new therapy in the treatment of MDD, like Zoranolone, if approved. One MDD population subset that stands apart in its need for new treatment options are those with MDD with elevated anxiety as a symptom of their depression. According to literature, which often refers to this population as anxious depression, up to two-thirds of people with MDD experience elevated anxiety symptoms as part of their depressions. Based on its mechanism of action and data seen in studies to date, we believe Zoranolone may be well-suited to help these people. We look forward to sharing more about MDD with elevated anxiety in the future, but be sure this is going to be a key focus going forward. If we're successful in our efforts, we've commercialized our partnership and engagement with all stakeholders, patients, healthcare professionals, payers, patient advocacy groups, and policymakers. These 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 Zoranilone, if approved. We remain on track to start the rolling NDA submission in MDD early this year and plan to complete the submission in the second half of 2022. As we shared previously, the planned NDA will include efficacy data from five studies. MDD-201B, Waterfall, Robin, Coral, and the Japanese study. In addition to data from the Shoreline study on repeat treatment efficacy sustained beyond the treatment period, and lastly, safety data from the entirety of the program. We also plan to submit an associated NDA with Zoranolone and PPD in the first half of 2023, pending completion and results of the Skylark study. We announced this morning that the FDA granted fast-track designation for Zoranolone and PPD. Fast-track designation is granted to drug candidates that treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Now turning to the recent advances in 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. In our last quarterly call, we announced that SAGE-718 was awarded fast-track designation by the FDA for development as a potential treatment for Huntington's disease, specifically Huntington's cognitive impairment. This designation was partially attributed to the promising early data we generated in our Phase I study of SAGE-718, which demonstrated improvements in cognitive performance in patients with Huntington's cognitive impairment. Patients are now enrolling in our Phase II placebo-controlled dimension study, evaluating SAGE-718 and in HD cognitive impairment, and we plan to expand our work in the syndication by initiating the Phase II placebo-controlled surveyor study in mid-2022 and begin an open-label extensive study in HD cognition in late 2022. We're also advancing SAGE-718 in patients with mild cognitive impairment due to Parkinson's disease. Phase II study evaluating SAGE-718 and patients with mild cognitive impairment, or MCI, due to Parkinson's in mid-2022. Finally, SAGE-718 is also being evaluated as a potential treatment for patients. We recently announced that SAGE-718 demonstrated improved performance from baseline on multiple cognitive function tests in patients with mild cognitive impairment and mild dementia due to Alzheimer's. The signals observed in the open-label luminary study were consistent with those seen in our Parkinson's and Huntington's trials. We plan to initiate a placebo-controlled Phase II study in SAGE-718 in patients with MCI and mild dementia due to Alzheimer's, which is expected to begin enrolling later this year. We've also made great progress on our neurology franchise, which features SAGE-324, another internally developed compound that is part of our collaboration with Biogen. Currently, SAGE 3-4 is being evaluated as a potential treatment for patients suffering from essential tremor, ET, and other neurological disorders. Jim will provide more insight in this program and updates for the year. I'd like to take a moment to thank the SAGE team for their hard work, commitment, and dedication on behalf of patients. 2021 was a data-rich year, and we realized important program advancements in multiple disease areas across all three of our brain health franchises. This work last year built a solid foundation for continued progress in 2022, and I'm excited by what the future holds for Sage. Additionally, I believe our balance sheet provides us the strategic and operational flexibility to continue to grow our pipeline as we continue to evaluate each investment diligently to ensure our decision-making positions us well in our efforts to create long-term value. In closing, I'm confident we have the opportunity to build on the momentum from the fourth quarter and throughout 2021 to to generate continued success in 2022 as we advance our journey to become the leader in brain health and a top tier biopharmaceutical company. Now I'd like to turn the call over to Jim for more detailed discussion of our recent coral data and a preview of our expectations for 2022. Jim?