Sage Therapeutics, Inc.

Good morning, welcome to Sage Therapeutics third quarter 2021 financial results conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the investors and media section of Sage's website at sagerx.com. This call is the property of Sage Therapeutics and recording, reproduction, or transmission of this call without the express written consent of Sage Therapeutics is strictly prohibited. Please note that this call is being recorded. I would now like to introduce Helen Rubenstein, Investor Relations at Sage.

Good morning, and thank you for joining Sage Therapeutics' third quarter 2021 financial results conference calls. 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 accomplishments during the quarter and some general context. We will also be joined by Jim Daugherty, our Chief Development Officer, who will review recent development progress across our programs, and Kimi Noguchi, our Chief Financial Officer, who will review financial results from the quarter. With that, I'll now turn the call over to Barry.

Thanks, Helen, and thank you, everyone, for joining us this morning. I'll begin the call by reviewing our recent corporate and clinical progress before turning the call to Jim to provide commentary on our clinical expectations for the remainder of 2021. Then Kimmy will provide an update on our financials. This year and quarter have been marked by significant progress for SAGE. We recently announced that following a pre-NDA meeting with the FDA, we and Biogen plan to submit an NDA for Xeranilone in MDD in the second half of 2022 and with an additional associated submission in PPD in the first half of 2023. We're pleased that we've reached alignment with the agency and believe we have a clear path for this submission. This brings us one step closer toward our goal of helping patients suffering from MDD and PPD. Now, let me take a step back to reflect on how we got here. We met with the agency in early 2020 and designed three distinct Phase III studies, two in MDD and one in PPD. The plan set in motion was for a positive study from any one of the three paths to support an NDA filing and subsequent approval, since it will provide the third positive pivotal study. Based on the positive results from the waterfall study, we believe that we have the necessary data to submit an NDA for Xeranalog. And we're delighted that our recent pre-NDA meeting with the FDA reaffirmed that belief. And now, in fact, we have four positive studies, MDD-201B, Robin, Waterfall, and the Shinugai Phase 2 study. The data we have generated in clinical development to date support our belief in the overall benefit-risk of Zoranolone. The plan NDA will include efficacy data from MDD-201B, Waterfall, Robin, and the Japanese study, as well as retreatment data from Shoreline, data from the ongoing pharmacology studies and CORAL, and safety from the entirety of the program. Importantly, The CORAL study is an adjunctive use study designed to demonstrate the benefits of Zoranilone when co-initiated with the standard antidepressant treatment, or ADT. Given the efficacy data we already have in hand to support the planned NDA filing and to align the CORAL study primary endpoint with the goal of the study, we announce today that the primary endpoint, HAMD17 change from baseline, will be measured at day three. This change is designed to allow us to demonstrate the rapid reduction of depressive symptoms. We'll also assess the impact of Zoranilone during the dosing period, as well as its safety profile. We believe if successful, these data may be important to inform potential real-world use if Zoranilone is approved. But we do not believe choral efficacy data will be required for the MDD filing pathways. CORAL data will, however, contribute to the overall safety database, regardless of the outcome of the primary endpoint. We've had a highly productive and transparent relationship with the agency and look forward to continuing to engage with them as we begin the rolling submission for Xeronalone, planned to commence in early 2022. We will work to ensure the totality of the landscape and nest programs are appropriately reflected in our planned NDA submission package and the product label if approved. We've recently also presented data from the landscape and nest programs at both the ECMP and annual site congress that reinforce the differentiated profiles around what we've seen to date in clinical development. Jim will walk you through the data we've presented, but I want to take a moment to highlight that we've seen a consistent profile for xeranolone across the totality of data. I would also like to take a moment to congratulate our colleagues at Shinugi, who recently presented positive results from a phase two study of Zoranilone conducted in Japan. These results further demonstrate the promise of Zoranilone for people living with MDD, and we look forward to continuing our relationship with them. As you can see from the totality of data collected across the landscape and nest program to date, Zoranilone has consistently demonstrated rapid and sustained reductions in depressive symptoms and a well-tolerated safety profile without the adverse events that are often associated with discontinuation of standard of care ADTs. We believe that we are well-positioned to be able to provide this important treatment to patients suffering from MDD and PPD, if approved. To this end, we're actively engaging in scientific exchange with KOLs and are pleased that many of them recognize both the value demonstrated across the Xoranilone clinical theta package as well as the potential for use in specific patient types they see in clinical practice. As we look to the next year, we anticipate building on this work. By remaining steadfast in our commitment to put MDD and PPD patients first in our Zoranolone development efforts, assembling the right team at the right time to execute on our planned NDA filing, and reinvesting our learnings from Zoranolone across our pipeline, we believe we are poised to make a difference for people with depression and other brain health disorders. We look forward to continuing to provide updates on Zoranilone as we pursue the initial NDA filing submission for MDD. Now, turning to our neurology franchise led by Sage 324, which is developed in-house and is part of our collaboration with Biogen. Sage 324 is currently being evaluated as a potential treatment for patients suffering from essential tremor and other neurological disorders, including epileptic form disorders, and Parkinson's disease. We believe that the pharmacologic characteristics of SAGE-324 are well suited to address the significant unmet need in patients suffering from essential tremor and other neurological diseases. Following the positive results from the kinetic study, we're preparing to initiate a Phase II dose-ranging study expected to commence later this year. The goal will be to optimize the dose and frequency with a good tolerability profile and a dosing schedule to maintain plasma concentrations that translate into sustained tremor symptom control. We look forward to providing updates on this study as we are able. Turning to our new oral franchise, where we are evaluating SAGE718, our wholly owned first-in-class NMDA receptor PAM, as a potential oral therapy for cognitive disorders associated with an MDA receptor dysfunction. This quarter, SAGE 718 received fast-track designation for development as a potential treatment for Huntington's disease from the FDA. As a reminder, we saw promising early data in a Phase I study of SAGE 718 in people with early Huntington's disease last year. We're on track with our plan to initiate a randomized placebo-controlled Phase II study with SAGE 718 in early to moderate Huntington's disease this year. The study F-positive will bring us one step closer to pursuing an initial regulatory indication for SAGE 718. I'm also pleased to announce that we plan to initiate a second randomized placebo phase two study with SAGE 718 in 2022. This will be in patients with Parkinson's disease cognitive dysfunction. We believe the study will meaningfully contribute to our understanding of SAGE 718 as we seek to provide a safe and efficacious treatment for patients suffering from this disorder. Lastly, SAGE 718 is also being evaluated in an ongoing luminary study as a potential treatment for Alzheimer's disease cognitive dysfunction. Today we announced the study is fully enrolled and we are on track to announce top line data from the study before the end of this year. As you can see, we've realized great progress across our brain health franchises so far this year. I'm also pleased to share progress on key corporate updates on today's call. This quarter, we are happy to welcome Chris Finecke, Chief Commercial Officer to SAGE, and announce that Vanessa Proctor has been elevated to serve as Head of External Affairs and joined our Executive Leadership Team. Additionally, Jim Dougherty, on the call with me, has assumed the role of Chief Development Officer. We've also elevated Mike Quirk to Senior Vice President Discovery and Research, where he will continue to build our research capabilities. As we expand and accelerate our efforts across our organization, and with so much to look forward to in the balance of 2021 and next year, I'm confident that their contributions across our organization will be instrumental to our collective progress toward becoming leaders in brain health. Today, we're also announcing the departure of Steve Keynes, SAGE's Chief Medical Officer. It's been Steve's goal since I met him to seek a CEO role, and he's fulfilling that today and will become CEO at a private biotech company. I'm thrilled for Steve and his new role. Steve has made significant contributions to SAGE over the past eight and a half years. We extend our thanks for his leadership in advancing our brain health programs and wish him success in his future endeavors. Steve has contributed to establishing SAGE as a leader in brain health and progressing programs across our pipelines. We're highly confident in the strong team that we have to continue to execute on our priorities. I invite Steve to say a few words, Steve.