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 second quarter ended June 30, 2020.

During the quarter, Sage initiated enrollment and dosing in two new trials with zuranolone 50 mg:

• Phase 3 SKYLARK Study (PPD-301) in postpartum depression (PPD)
• Phase 3 WATERFALL Study (MDD-301B) in major depressive disorder (MDD)
  • Based on strong enrollment to date, topline data from this study is now anticipated in first half of 2021

In addition, Sage initiated dosing in the 50 mg cohort of the open-label Phase 3 SHORELINE Study and is on-track to initiate dosing in 2H 2020 in the Phase 3 CORAL Study (MDD-305) investigating zuranolone 50 mg as an acute rapid response therapy (RRT) in patients with MDD when co-initiated with a newly administered standard antidepressant therapy. The Company also initiated dosing in the Phase 2 KINETIC Study evaluating SAGE-324 in patients with essential tremor and is on-track to initiate the Phase 2 PARADIGM Study in the second half of 2020 evaluating SAGE-718 in patients with Parkinson’s disease (PD) with impaired cognitive function.

Sage also reported results from the 6-month follow-up cohort with zuranolone 30 mg from the MOUNTAIN study. There were no symptoms of withdrawal observed after discontinuation of zuranolone (Day 14) and 74.5% of patients who responded to zuranolone maintained their response at the last follow-up at Day 182. Zuranolone was generally well-tolerated and showed a similar safety profile as seen in earlier studies.

“We have created a novel drug company successfully able to convert our chemical equity into a rich pipeline of clinical assets that are new chemical entities, not repurposed molecules,” said Jeff Jonas, M.D., chief executive officer at Sage Therapeutics. “Even in the face of the difficulties currently challenging the world, I’m pleased to report that the team at Sage is executing across all three brain health franchises and we expect to report on numerous catalysts in the next 18 months.”

Portfolio UpdatesSage 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 FranchiseSage’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 received breakthrough therapy designation from the U.S. 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, if successful, for 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 is anticipated in 2021.
  • WATERFALL (MDD-301B) Study investigating zuranolone for as-needed, or episodic, treatment in MDD:
    • Placebo-controlled trial evaluating a two-week course of zuranolone 50 mg in patients with MDD, with additional short-term follow-up.
    • Based on strong enrollment to date, with more than 50% enrolled, topline data from this study is now anticipated in the first half of 2021.

Sage is on-track to commence 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 an open-label antidepressant, in patients with MDD, with additional short-term follow-up.
  • Topline data from this study is anticipated in 2021.

Additional study updates:

• SHORELINE Study (MDD-303): The Company is on track to report topline data in the second half of 2020 from patients with MDD who received zuranolone 30 mg in the SHORELINE Study, designed to evaluate safety and tolerability of as-needed repeat treatment over a 1-year period.
  • Patient dosing has begun in a new 50 mg cohort of patients with MDD; enrollment is ongoing.

• MOUNTAIN Study 6-month follow-up data: As part of the MOUNTAIN Study, subjects were offered the opportunity to participate in a 6-month, blinded follow-up to assess durability of response. The study was not powered to detect statistical significance beyond the Day 15 endpoint. More detailed data will be prepared for presentation and publication.
  • Of the subjects who were dosed in the MOUNTAIN Study, approximately 50% agreed to join the 6-month follow-up period and nearly 75% of patients who responded to zuranolone 30 mg at Day 15 maintained their response rate at the last follow-up on Day 182.

Safety:

• No drug-related adverse events, changes in laboratories, ECG measures, vital signs, or suicidality ratings were present over the long-term following exposure to zuranolone. Zuranolone was generally well-tolerated and showed a similar safety profile as seen in earlier studies.
• There were no signals of withdrawal or rebound after treatment with zuranolone was completed.

Durability of treatment:

• In subjects with response after the 14-day treatment period (Day 15), a large majority maintained this response throughout the 6-month follow-up regardless of arm.
  • Out of responders to zuranolone 30 mg at Day 15 (N=77), a large majority (74.5%) maintained their response rate at the last follow up at Day 182.
  • This continued benefit was seen with all efficacy measures over the 6-month follow-up period: (17-item Hamilton Rating Scale for Depression (HAM-D), Clinician Global Impression – Improvement (CGI-I), Clinician Global Impression – Severity (CGI-S).

• Sage’s collaboration with Shionogi & Co., Ltd. is progressing, with Shionogi initiating a Phase 2 trial with zuranolone in Japan for the treatment of MDD. Under terms of 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.

• Sage is also currently evaluating the ongoing zuranolone clinical pharmacology and safety program and plans to finalize requirements to support a potential future NDA with the FDA.

• ZULRESSO™ (brexanolone) CIV injection:
  • Revenue in the second quarter of 2020 from sales of ZULRESSO was $1.1 million, compared to $2.3 million in the first quarter of 2020. In April 2020, as a part of the Company’s restructuring, Sage downsized commercial efforts, including elimination of its entire salesforce. The Company now has a small commercial team with a primary focus on working with healthcare providers and supporting women with PPD in geographies with active, ZULRESSO treating sites.
  • The rapid spread of COVID-19 in the U.S. resulted in multiple sites of care pausing treatment of new patients with ZULRESSO during the quarter. Concerns about exposure to the virus have also caused a significant reduction in the number of women with PPD seeking treatment with ZULRESSO and in physicians willing to prescribe it. Given the ongoing surge in the number of cases of COVID-19 in the U.S. and continuing concerns about the pandemic across the country, the Company expects the significant adverse impact of the pandemic on ZULRESSO revenues to continue. The Company does not plan to provide revenue guidance for the balance of 2020.
  • The Company has received clearance from the U.S. 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).
    • Additional information about this program will be provided during Sage’s upcoming FutureCast investor day planned for September.

Neurology FranchiseSAGE-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.

• SAGE-324: Sage initiated enrollment and dosing in the KINETIC Study (324-ETD-201), a placebo-controlled Phase 2 study evaluating the safety and efficacy of SAGE-324 in patients with ET. Patients will receive a once-daily, four-week course of SAGE-324 60 mg or placebo.
  • Topline data from this study is anticipated in 4Q 2020/1Q 2021.

Neuropsychiatry FranchiseSAGE-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), Parkinson’s disease (PD) and Alzheimer’s disease (AD).

• SAGE-718: The Company is on-track to initiate the PARADIGM Study (718-CNP-201), a Phase 2a open-label study in 2020 evaluating SAGE-718 in patients with PD cognitive dysfunction.
  • Results from this study will inform potential advancement of SAGE-718 into further development.
  • Topline data from this study is anticipated in 2H 2020.

Anticipated Upcoming Milestones

2H 2020

• Zuranolone:
  • Initiate dosing in Phase 3 CORAL (MDD-305) Study evaluating a two-week course of zuranolone 50 mg, when co-initiated with an open-label anti-depressant, as an acute rapid response therapy in patients with MDD.
  • Report topline data from Phase 3 SHORELINE (MDD-303 – 30 mg) Study.
• Brexanolone:
  • Initiate Phase 3 study in patients with advanced COVID-19 related acute respiratory distress syndrome (ARDS).
• SAGE-718:
  • Report topline data from Phase 2a study in patients with Parkinson’s disease cognitive dysfunction.
• SAGE-324:
  • Report topline data from Phase 2 placebo-controlled study in ET (4Q 2020/1Q 2021).

2021

• Zuranolone:
  • Report topline data from Phase 3 WATERFALL Study (1H 21).
  • Report topline data from Phase 3 SKYLARK Study.
  • Report topline data from Phase 3 CORAL Study.
  • Report topline data from Phase 3 SHORELINE Study (50 mg).

Financial Results for the Second Quarter 2020

• Revenue: Sage recorded $1.1 million in net revenue in the second quarter of 2020 from sales of ZULRESSO, compared to $0.5 million for the same period in 2019. Sage recorded no collaboration revenue in the second quarter of 2020 compared to $0.4 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 June 30, 2020 were $759 million compared to $875 million at March 31, 2020.
• R&D Expenses: Research and development expenses were $73.3 million, including $10.1 million of non-cash stock-based compensation expense, in the second quarter of 2020 compared to $89.1 million, including $13.7 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 and the decrease in non-cash stock-based compensation expense.
• SG&A Expenses: Selling, general and administrative expenses were $38.2 million, including $12.1 million of non-cash stock-based compensation expense, in the second quarter of 2020 compared to $88.2 million, including $21.1 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.
• Restructuring Expenses: Restructuring expenses were $28.4 million in the second quarter of 2020 compared to none for the same period in 2019.
• Net Loss:Net loss was $136.3 million for the second quarter of 2020, compared to $168.2 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.