CAMBRIDGE, Mass.--(BUSINESS WIRE)--Today, Sage Therapeutics, Inc. (NASDAQ: SAGE), a biopharmaceutical company committed to developing novel therapies with the potential to transform the lives of people with debilitating disorders of the brain, reported business highlights and financial results for the fourth quarter and full year ended December 31, 2020.

“Although 2020 was a challenging year, Sage’s commitment to rigorous science, innovation and disciplined execution resulted in significant progress across all of our brain health franchises, strongly positioning us in our efforts to deliver revolutionary medicines to millions of patients,” said Barry Greene, chief executive officer at Sage Therapeutics. “Our collaboration with Biogen enhances our strategic, financial, and operational flexibility, enabling our plans to expand and accelerate our pipeline and extending the potential impact of our product candidates, if we’re successful, to more than 450 million patients worldwide. In the first months of 2021, we’ve already begun to realize this expansion and acceleration with the progression of multiple early-stage programs. I believe 2021, with 10 expected data readouts, will be a transformational year for Sage in our mission to become the leading brain health company in the next five years.”

KEY 2020 UPDATESCollaboration with Biogen: In November 2020, Sage and Biogen entered into a global collaboration and license agreement to jointly develop and commercialize zuranolone (SAGE-217) for major depressive disorder (MDD), postpartum depression (PPD) and other disorders, and SAGE-324 for essential tremor (ET) and other disorders.

• Total potential value of the collaboration is $3.1 billion, including $1.5 billion received at closing on December 31, 2020, comprised of an upfront payment of $875 million and a $650 million equity investment, and $1.6 billion in potential milestone payments.
• Transaction included purchase by Biogen of 6,241,473 shares of Sage common stock at a 40% premium.
• Sage and Biogen are jointly developing, and, if successful, will jointly commercialize, zuranolone and SAGE-324 in the U.S. Biogen has an exclusive license to develop and commercialize zuranolone and SAGE-324 outside of the U.S., excluding rights to zuranolone in Japan, Taiwan and South Korea.

Zuranolone SHORELINE Study data: In October 2020, Sage reported positive, interim topline results from a July data cut of the ongoing Phase 3 open-label SHORELINE Study of zuranolone in MDD. The SHORELINE Study is designed to evaluate the safety and tolerability of zuranolone in adults for up to one year.

Interim topline data from the SHORELINE Study showed:

• Zuranolone was generally well-tolerated at the 30 mg dose and by the initial patients treated with the 50 mg dose with an adverse event profile consistent with that seen in earlier trials.
• Nearly half of trial participants with a positive response to the initial 14-day course of zuranolone 30 mg did not need an additional zuranolone treatment course and more than 70% needed two or fewer zuranolone treatment courses.
  • In the 30 mg cohort, the most common adverse events (reported ?5%) were: somnolence (69; 9.5%), headache (63; 8.7%), and dizziness (39; 5.4%). Most adverse events were mild or moderate.
• At Day 15 of the first course of zuranolone in the initial group of patients who only received 50 mg in the study (n=52), ~75% achieved response (decrease in HAMD-17 baseline score of ?50%) and ~48% achieved remission (HAM-D ?7).
  • Safety data available from the 50 mg cohort was similar to that seen in patients who received 30 mg zuranolone. Events >5% of somnolence, dizziness, sedation, headache and tremor were observed to be more frequent in the 50 mg cohort, but were similar in severity to the events seen with 30 mg. Most adverse events were mild or moderate. In patients who received zuranolone 50 mg after having received 30 mg previously, higher rates and levels of intensity with AEs of >5% (sedation, somnolence) were noted.

Corporate restructuring: In April 2020, Sage completed a restructuring intended to enable the Company to advance its corporate strategy and pipeline throughout the COVID-19 pandemic and beyond.

PORTFOLIO UPDATESSage is advancing a portfolio of clinical programs featuring internally discovered novel chemical entities with the potential to become differentiated products designed to improve brain health by targeting the GABAA and NMDA receptor systems. Dysfunction in these systems is thought to be at the core of numerous neurological and neuropsychiatric disorders.

Depression Franchise

Sage’s depression franchise features zuranolone, Sage’s next-generation positive allosteric modulator (PAM) of GABAA receptors being evaluated in clinical development as a treatment for various affective disorders, and ZULRESSO® (brexanolone) CIV injection, approved by the U.S. Food and Drug Administration (FDA) as the first treatment specifically indicated for PPD. Zuranolone has received breakthrough therapy designation from the FDA for the treatment of MDD.

Zuranolone is being evaluating as a potential rapid-acting, short-course treatment for PPD and MDD in the NEST and LANDSCAPE clinical trial programs. Sage initiated three Phase 3 clinical studies in 2020. If successful, these studies, along with the rest of the program, may support paths to approval with three distinct opportunities to address patient needs: PPD, acute rapid response therapy (RRT) in MDD when co-initiated with a new standard antidepressant, and as-needed treatment of MDD.

The Company expects the following zuranolone data readouts in 2021:

• 1H 2021:
  • WATERFALL (MDD-301B) Study: A placebo-controlled Phase 3 trial evaluating a two-week course of zuranolone 50 mg in patients with MDD, with additional short-term follow-up. Today the Company announced the WATERFALL Study is closed to enrollment, with more than 525 patients expected to be randomized in the study. Data are anticipated in the first half of 2021.

• Mid-2021:
  • SHORELINE (MDD-303) Study 30 mg Cohort - Full Data: An open-label Phase 3 trial designed to naturalistically follow patients with MDD and evaluate the safety and tolerability of zuranolone 30 mg in adults for up to one year. The Company announced positive interim topline data from this cohort in October 2020.

• Late 2021:
  • SKYLARK (PPD-301) Study: A placebo-controlled Phase 3 trial evaluating a two-week course of zuranolone 50 mg in women with PPD, with additional short-term follow-up.
  • CORAL (MDD-305) Study: A placebo-controlled Phase 3 trial evaluating a two-week course of zuranolone 50 mg, when co-initiated with a new antidepressant, in patients with MDD, with additional short-term follow-up.
  • SHORELINE (MDD-303) Study 50 mg Cohort: An open-label Phase 3 trial designed to naturalistically follow patients with MDD and evaluate the safety and tolerability of zuranolone 50 mg in adults for up to one year.

Sage is also evaluating the ongoing zuranolone clinical pharmacology and safety program and plans to align with FDA on data to support a potential future new drug application (NDA) with the FDA. Additional development plans for zuranolone will be confirmed and announced as part of the Company’s strategic collaboration with Biogen.

Additionally, Sage’s collaboration with Shionogi & Co., Ltd. is progressing. In 2020, Shionogi initiated a Phase 2 trial with zuranolone in Japan for the treatment of MDD. Shionogi anticipates that this Phase 2 study will finish in the third quarter of 2021. Under the terms of the collaboration, Shionogi is responsible for all clinical development, regulatory filings and commercialization of zuranolone for MDD, and potentially other indications, in Japan, Taiwan and South Korea.

Neurology Franchise

SAGE-324, a next-generation PAM of GABAA receptors and Sage’s lead neurology program, is in development as a potential oral therapy for neurological conditions, such as ET, epilepsy and Parkinson’s disease (PD).

The following milestones are expected for the neurology franchise in 2021:

• Early 2021:
  • KINETIC (324-ETD-201) Study: The Company expects topline data from the KINETIC Study, a placebo-controlled Phase 2 trial evaluating the safety and efficacy of SAGE-324 in patients with ET to readout in early 2021.

• Late 2021:
  • If data from the KINETIC Study support further development, Sage anticipates initiating a placebo-controlled Phase 2b trial with SAGE-324 in ET in late 2021 to explore dose and frequency, including potential formulations.

Additional development plans for SAGE-324 will be confirmed and announced as part of the Company’s strategic collaboration with Biogen.

Neuropsychiatry Franchise

SAGE-718, Sage’s first-in-class NMDA receptor PAM and lead neuropsychiatric drug candidate, is in development as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction, potentially including Huntington’s disease (HD), PD and Alzheimer’s disease (AD).

Positive data with SAGE-718 to date include results from a Phase 1 open-label study evaluating the safety and pharmacokinetics of SAGE-718 in a cohort of patients with early HD. In that study, SAGE-718 was well tolerated with no serious adverse events or adverse events leading to treatment discontinuation and patients demonstrated improved performance, compared to baseline, on assessments of executive functioning, a core feature of early HD.

Ongoing trials with SAGE-718:

• PARADIGM Study: Phase 2a open-label trial evaluating SAGE-718 in patients with PD cognitive dysfunction. The Company initiated enrollment and dosing in September 2020.
• LUMINARY Study: Phase 2a open-label trial evaluating SAGE-718 in patients with AD mild cognitive impairment and mild dementia. The Company initiated enrollment and dosing in early 2021.

The following milestones are expected for the neuropsychiatry franchise in 2021:

• Early 2021:
  • PARADIGM (718-CNP-201) Study: The Company anticipates topline data from the PARADIGM Study in early 2021.

• Late 2021:
  • LUMINARY (718-CNA-201) Study: The Company anticipates topline data from the LUMINARY Study in late 2021.

Additionally, the Company expects to initiate a placebo-controlled Phase 2 trial with SAGE-718 in late 2021. Details of this trial will be informed by results from the Phase 2a studies and earlier work.

Early Development

Sage expects to complete certain Phase 1 clinical studies for two programs in its early development pipeline in 2021, SAGE-689 (single ascending dose) and SAGE-904 (single ascending dose and multiple ascending dose).

• SAGE-689: is an intramuscular GABAA receptor PAM in development as a potential therapy for disorders associated with acute GABA hypofunction.
• SAGE-904: is Sage’s second NMDA receptor PAM product candidate in development as a potential oral therapy for disorders associated with NMDA hypofunction.

Results from the Phase 1 studies will inform further development of these programs.

Additionally, the Company recently announced plans to advance SAGE-319 and SAGE-421 to preclinical studies.

• SAGE-319: is an oral, extrasynaptic GABAA receptor preferring PAM that Sage plans to study for potential use in disorders of social interaction.
• SAGE-421: is an oral, NMDA receptor PAM that Sage plans to study for potential use in neurodevelopmental disorders and cognitive recovery and rehabilitation.

Other Development Opportunities

Sage initiated a Phase 3 trial with brexanolone in patients with advanced COVID-19 related acute respiratory distress syndrome (ARDS) in the fourth quarter of 2020 under the Coronavirus Treatment Acceleration Program (CTAP). The Company expects topline data from this trial in 2021.

ANTICIPATED 2021 MILESTONES

Early 2021:

• SAGE-324:
  • Report topline data from Phase 2 placebo-controlled KINETIC Study in ET
• SAGE-718:
  • Report topline data from Phase 2a PARADIGM open-label, signal finding study in patients with PD cognitive dysfunction

Mid-2021:

• Zuranolone:
  • Report topline data from Phase 3 WATERFALL Study (1H21)
  • Report full data from Phase 3 SHORELINE Study 30mg cohort

Late 2021:

• Zuranolone:
  • Report topline data from Phase 3 SKYLARK Study
  • Report topline data from Phase 3 CORAL Study
  • Report topline data from Phase 3 SHORELINE Study 50mg cohort
• SAGE-324:
  • Initiate Phase 2b study in ET
• SAGE-718:
  • Report topline data from Phase 2a LUMINARY open-label, signal finding study in patients with AD mild cognitive impairment and mild dementia
  • Initiate placebo-controlled Phase 2 study
• Brexanolone:
  • Report topline data from Phase 3 study in patients with advanced COVID-19 related ARDS
• SAGE-689 & SAGE-904:
  • Complete planned Phase 1 studies (SAD for SAGE-689 and SAD/MAD for SAGE-904)

FINANCIAL RESULTS FOR THE FOURTH QUARTER AND FULL YEAR 2020

• Cash Position: Cash, cash equivalents, restricted cash, and marketable securities as of December 31, 2020 were $2.1 billion compared to $0.7 billion at September 30, 2020. The increase is from the receipt of cash from Biogen for the upfront under the collaboration and license agreement of $875 million and the stock purchase of $650 million.

• Revenue: Sage recorded $1.1 billion in net revenue in the fourth quarter of 2020, comprised of $1.1 billion of collaboration revenue from Biogen and $1.7 million from sales of ZULRESSO, compared to $2.0 million for the same period in 2019, which consisted of revenue from sales of ZULRESSO. For the year ended December 31, 2020, Sage recorded $1.1 billion in net revenue comprised of $1.1 billion of collaboration revenue from Biogen and $6.7 million from sales of ZULRESSO, compared to $6.9 million for the same period in 2019, which consisted of $4.0 million in revenue from sales of ZULRESSO and $2.9 million of collaboration revenue from Shionogi. The collaboration revenue of $1.1 billion from Biogen recorded in the fourth quarter of 2020 consisted of an upfront payment of $875 million plus $232.5 million in excess proceeds from the equity investment under the stock purchase agreement.

• R&D Expenses: Research and development expenses were $81.7 million, including $10.1 million of non-cash stock-based compensation expense, in the fourth quarter of 2020 compared to $91.3 million, including $11.4 million of non-cash stock-based compensation expense, for the same period in 2019. For the year ended December 31, 2020, R&D expenses were $292.7 million, including $42.4 million of non-cash stock-based compensation expense, compared to $368.8 million, including $62.9 million of non-cash stock-based compensation expense, for the same period in 2019. The decreases in R&D expenses were primarily due to a decrease of $30.2 million in expenses for zuranolone, primarily as a result of completion of the MOUNTAIN Study and decreased spending for clinical pharmacology studies, partially offset by an increase in spending for the WATERFALL Study and the SKYLARK Study. For the year, non-cash stock-based compensation expense decreased because the Company incurred no expense in 2020 for performance-based grants, and incurred $14.0 million of expense for such grants as R&D expenses in 2019.

• SG&A Expenses: Selling, general and administrative expenses were $53.5 million, including $10.6 million of non-cash stock-based compensation expense, in the fourth quarter of 2020 compared to $85.1 million, including $19.3 million of non-cash stock-based compensation expense, for the same period in 2019. For the year ended December 31, 2020, SG&A expenses were $197.0 million, including $51.8 million of non-cash stock-based compensation expense, compared to $345.8 million, including $90.3 million of non-cash stock-based compensation expense, for the same period in 2019. The decreases in SG&A expenses were primarily due to the restructuring that the Company announced during the second quarter of 2020. For the year, non-cash stock-based compensation expense decreased because the Company incurred no expense in 2020 for performance-based grants, and incurred $13.2 million of expense for such grants as SG&A expenses in 2019.

• Net Income (loss): Net income was $974.9 million for the fourth quarter of 2020, compared a net loss of $168.7 million for the same period in 2019. For the year ended December 31, 2020, net income was $606.1 million, compared to a net loss of $680.2 million for the same period in 2019. In both periods, the increase was due to the collaboration revenue from Biogen.

FINANCIAL GUIDANCE

• Sage anticipates cash, cash equivalents, restricted cash, and marketable securities of more than $1.7 billion at end of 2021.
• The Company does not anticipate receipt of any milestone payments from collaborations in 2021.

About Sage Therapeutics

Sage Therapeutics is a biopharmaceutical company committed to developing novel therapies with the potential to transform the lives of people with debilitating disorders of the brain. We are pursuing new pathways with the goal of improving brain health, and our depression, neurology and neuropsychiatry franchise programs aim to change how brain disorders are thought about and treated. Our mission is to make medicines that matter so people can get better, sooner. For more information, please visit www.sagerx.com.