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 third quarter ended September 30, 2020.

“Today I’m pleased to report that our clinical programs across three franchises remain on track, with a series of key milestones anticipated over the next 12 to 18 months,” said Mike Cloonan, chief operating officer at Sage Therapeutics. “During the third quarter, we continued progress across our deep and robust clinical pipeline, a pipeline that spans multiple disease states with programs in early, mid and late stage development. The Sage team continues to execute well during the COVID-19 pandemic and remains determined to provide much needed options to patients suffering with debilitating brain health disorders.”

Recent updates

Sage recently reported positive, interim topline results from a July data cut of the ongoing Phase 3 open-label SHORELINE Study of zuranolone in major depressive disorder (MDD). The data analyzed to date show that zuranolone was generally well-tolerated in the 30 mg dose and among the initial patients treated with the 50 mg dose. Adverse events reported in the trial during the period analyzed were generally consistent with results seen in previous zuranolone clinical trials.

As the first naturalistic, longitudinal, clinical development trial conducted in MDD, the SHORELINE Study provides real world insight into the potential use of zuranolone, if successfully developed and approved as an as-needed treatment for MDD, and builds on the data assembled in the LANDSCAPE clinical program. The Company plans to report comprehensive data from the 30 mg dose of the SHORELINE Study in the first half of 2021 and will include additional analyses of the data set.

Portfolio Updates

Sage is advancing a portfolio of novel, new 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 postpartum depression (PPD). Zuranolone has received breakthrough therapy designation from the FDA for the treatment of MDD.

• Zuranolone ongoing studies: Sage is evaluating the potential of zuranolone as a rapid-acting, short-course treatment for PPD and MDD. Sage recently initiated three new short-term clinical studies in 2020, with the potential along with the rest of the program, if successful, to support three distinct indications: PPD, acute rapid response therapy (RRT) in MDD when co-initiated with a new standard antidepressant, and as-needed, or episodic, treatment of MDD. Enrollment and dosing are now ongoing in two of these trials:
  • SKYLARK (PPD-301) Study investigating zuranolone as an oral therapy in women with PPD:
    • Placebo-controlled trial evaluating a two-week course of zuranolone 50 mg in women with PPD, with additional short-term follow-up.
    • Topline data from this study are anticipated in 2021.
  • WATERFALL (MDD-301B) Study investigating zuranolone for the as-needed, or episodic, treatment of MDD:
    • Placebo-controlled trial evaluating a two-week course of zuranolone 50 mg in patients with MDD, with additional short-term follow-up.
    • Topline data from this study are anticipated in the first half of 2021.

Sage expects to initiate dosing of the third new zuranolone Phase 3 trial in 2020:

• CORAL (MDD-305) Study investigating zuranolone for acute RRT in patients with MDD when co-initiated with a newly administered standard antidepressant therapy:
  • Placebo-controlled trial evaluating a two-week course of zuranolone 50 mg, when co-initiated with a new open-label antidepressant, in patients with MDD, with additional short-term follow-up.
  • Topline data from this study are anticipated in 2021.

• Sage is also currently evaluating the ongoing zuranolone clinical pharmacology and safety program and plans to finalize requirements to support a potential future new drug application (NDA) with the FDA.
• ZULRESSO® (brexanolone) CIV injection:
  • Revenue in the third quarter of 2020 from sales of ZULRESSO was $1.6 million, compared to $1.5 million in the third quarter of 2019. As previously announced, due to the ongoing impact of the COVID-19 pandemic, the Company expects de minimis revenue for the balance of 2020, and expects future revenue growth to be limited even after the pandemic as a result of the significant barriers to treatment and the refocus of Sage’s commercialization efforts after the April 2020 restructuring.
  • The Company has received clearance from the FDA, under the Coronavirus Treatment Acceleration Program (CTAP), to initiate a Phase 3 study with brexanolone in patients with advanced COVID-19 related acute respiratory distress syndrome (ARDS). The Company expects to initiate patient dosing in this study in the fourth quarter of 2020.
    • Topline data from this study are anticipated in 2021.

Neurology Franchise

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

• KINETIC Study: The KINETIC Study (324-ETD-201), a placebo-controlled Phase 2 study evaluating the safety and efficacy of SAGE-324 in patients with ET is ongoing. Patients in the study receive a once-daily, four-week course of SAGE-324 60 mg or placebo.
  • Topline data from this study are now anticipated in 1Q 2021.

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).

• PARADIGM Study: The Company initiated enrollment and dosing in the PARADIGM Study (718-CNP-201), a Phase 2a open-label study evaluating SAGE-718 in patients with PD cognitive dysfunction.
  • Topline data from this study are now anticipated in the first quarter of 2021.

• LUMINARY Study: The Company expects to initiate dosing in the LUMINARY Study (718-CNP-201), a Phase 2a open-label study evaluating SAGE-718 in patients with AD cognitive dysfunction and mild dementia in the fourth quarter of 2020.

Results from these studies will inform potential advancement of SAGE-718 into further development.

Corporate Updates

During the third quarter, the Company strengthened its leadership with two key additions:

• Barry Greene was appointed to Sage’s Board of Directors. He was most recently President of Alnylam Pharmaceuticals, Inc.

• Tammy Phinney joined the Company’s management team as senior vice president, regulatory affairs. Her extensive experience leading regulatory functions in the neurology therapeutic area over the last 15 years is well-aligned with Sage’s significant regulatory needs as the Company is anticipating several potential FDA engagements as its pipeline advances. Most recently, she served as Vice President, Head of US, Regulatory Affairs at EMD Serono.

The Company also hosted the 2nd annual “FutureCast: An R&D Portfolio Review” in the third quarter to review the Company’s research and development strategy, and clinical progress in its key depression, neurology, and neuropsychiatry franchise programs.

Anticipated Upcoming Milestones

Q4 2020

• Zuranolone:
  • Initiate dosing in Phase 3 CORAL Study (MDD-305) evaluating zuranolone 50 mg, when co-initiated with a new open-label antidepressant, as an acute rapid response therapy in patients with MDD.
• Brexanolone:
  • Initiate dosing in Phase 3 study in patients with advanced COVID-19 related acute respiratory distress syndrome (ARDS).
• SAGE-718
  • Initiate dosing in Phase 2a LUMINARY open-label, signal finding study in patients with Alzheimer’s disease cognitive dysfunction and mild dementia.

2021

• Zuranolone:
  • Report topline data from Phase 3 WATERFALL Study (1H 2021).
  • Report topline data from Phase 3 SKYLARK Study.
  • Report topline data from Phase 3 CORAL Study.
  • Report topline data from Phase 3 SHORELINE Study (30 mg full data set – 1H 2021; 50 mg topline data – 2H 2021).
• SAGE-324:
  • Report topline data from Phase 2 placebo-controlled KINETIC Study in essential tremor (1Q 2021).
• SAGE-718:
  • Report topline data from Phase 2a PARADIGM open-label, signal finding study in patients with Parkinson’s disease cognitive dysfunction (1Q 2021).
• Brexanolone:
  • Report topline data from Phase 3 study in patients with advanced COVID-19 related ARDS.

Financial Results for the Third Quarter 2020

• Revenue: Sage recorded $1.6 million in net revenue in the third quarter of 2020 from sales of ZULRESSO, compared to $1.5 million for the same period in 2019. Sage recorded no collaboration revenue in the third quarter of 2020 compared to $2.1 million in collaboration revenue from Shionogi & Co., Ltd. related to reimbursement of product expense for the same period in 2019.

• Cash Position: Cash, cash equivalents, restricted cash, and marketable securities as of September 30, 2020 were $671 million compared to $759 million at June 30, 2020.

• R&D Expenses: Research and development expenses were $74.1 million, including $9.9 million of non-cash stock-based compensation expense, in the third quarter of 2020 compared to $102.1 million, including $17.1 million of non-cash stock-based compensation expense, for the same period in 2019. The decrease in R&D expenses was primarily related to the completion of the MOUNTAIN Study, a Phase 3 clinical trial of zuranolone in MDD; the decrease in non-cash stock-based compensation expense and decreased spending for clinical pharmacology studies, partially offset by an increase in spending for the WATERFALL Study, a Phase 3 clinical trial of zuranolone in MDD.

• SG&A Expenses: Selling, general and administrative expenses were $35.1 million, including $10.2 million of non-cash stock-based compensation expense, in the third quarter of 2020 compared to $88.5 million, including $26.6 million of non-cash stock-based compensation expense, for the same period in 2019. The decrease in SG&A expenses was primarily due to the restructuring that the Company announced during the second quarter of 2020.

• Net Loss: Net loss was $105.7 million for the third quarter of 2020, compared to $180.0 million for the same period in 2019.

Financial Guidance

• Sage anticipates a cash balance of at least $550 million at end of 2020, which the Company anticipates will support operations into 2022 based on current operating plans.

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.