Completion of rolling NDA submission for
zuranolone in MDD and PPD on track for December 2022
Presented additional data across pipeline
programs at key medical congresses including data on zuranolone as
an investigational oral, once-daily, 14-day treatment for MDD and
PPD
Company appoints Laura Gault, M.D., Ph.D., as
Chief Medical Officer, enhancing management team and advancing
Sage’s position as a leader in brain health and a top-tier
biopharmaceutical company
Cash and cash equivalents, anticipated funding
from ongoing collaborations, and potential revenue, expected to
support operations into 2025
Sage Therapeutics, Inc. (Nasdaq: SAGE), a biopharmaceutical
company leading the way to create a world with better brain health,
today reported business highlights and financial results for the
third quarter ended September 30, 2022.
“This has been an important year for Sage, marked by the
execution of significant milestones across our franchises. Looking
ahead, we remain focused on the completion of the NDA submission
for zuranolone in MDD and PPD, and are well into commercialization
preparations to support a potential launch. Patients with
depression are desperate to find new medicines that are safe,
rapid-acting, short course, and have a sustained effect. We believe
zuranolone, if approved, has the potential to deliver a new
treatment option for patients,” said Barry Greene, Chief Executive
Officer at Sage Therapeutics. “In parallel, our team is advancing
multiple clinical studies across our pipeline that span our
neuropsychiatry and neurology franchises. I am proud of the
tremendous progress our team has made on behalf of patients this
year and am energized by the momentum we have going into 2023 and
beyond.”
Third Quarter 2022 Portfolio
Updates
Sage 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 Association (FDA) as
the first treatment specifically indicated for postpartum
depression (PPD). Zuranolone has received Breakthrough Therapy and
Fast Track Designation for the treatment of major depressive
disorder (MDD) and Fast Track Designation for the treatment of PPD
from the FDA.
Zuranolone is being evaluated as a potential rapid-acting,
once-daily, oral two-week treatment for MDD and PPD in the
LANDSCAPE and NEST clinical development programs, respectively.
Across seven positive clinical trials, zuranolone has demonstrated
rapid and sustained relief of depressive symptoms in people with
MDD and PPD.
In the third quarter, Sage and its collaborator, Biogen,
announced multiple new analyses across the development program for
zuranolone, presented at the 2022 Psych Congress and the 35th
European College of Neuropsychopharmacology (ECNP) Congress. The
presentations included new analyses from the SHORELINE Study and
Health Economics and Outcomes Research, as well as the first
presentation of data from the SKYLARK Study.
Sage and Biogen continue to advance a rolling NDA submission for
zuranolone for the treatment of both MDD and PPD, which is on track
to be completed in December 2022.
The Company expects to achieve the following milestones across
its depression franchise in 2022:
- Late 2022:
- Complete NDA submission for zuranolone in MDD and PPD (December
2022).
- Additional presentations of zuranolone data throughout
2022.
Neuropsychiatry Franchise
Sage’s neuropsychiatry franchise features SAGE-718, the
Company’s first-in-class NMDA receptor PAM and lead
neuropsychiatric drug candidate, 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
received Fast Track Designation from the FDA for development as a
potential treatment for HD.
Sage is advancing a robust clinical program for SAGE-718 with
multiple ongoing or planned Phase 2 studies, including the
DIMENSION and SURVEYOR Studies in people with HD cognitive
impairment, the lead indication for SAGE-718, the PRECEDENT Study
in people with mild cognitive impairment (MCI) associated with PD
and the LIGHTWAVE Study in people with MCI and mild dementia due to
AD. Sage is currently enrolling in the following Phase 2
studies:
- DIMENSION (CIH-201) Study: The
DIMENSION Study is a double-blind, placebo-controlled study in
people with HD cognitive impairment. The study is designed to
evaluate the efficacy of once-daily SAGE-718 dosed over three
months, with a target enrollment of approximately 178 people. Sage
expects the DIMENSION Study to include more than 40 clinical
sites.
- SURVEYOR (CIH-202) Study: The
SURVEYOR Study is a double-blind, placebo-controlled study in
people with HD cognitive impairment and healthy volunteers, with
the goal of generating evidence linking efficacy signals on
cognitive performance to domains of real-world functioning.
- PRECEDENT (CNP-202) Study: The
PRECEDENT Study is a double-blind, placebo-controlled study in
people with MCI due to PD. The study is designed to evaluate the
safety and efficacy of SAGE-718 in people with MCI due to PD over
42 days, followed by a controlled follow-up period.
The Company expects to achieve the following milestones across
its neuropsychiatry franchise in 2022:
- Late 2022:
- Phase 3 Open-label Safety Study in HD
(CIH-301): Initiate an open-label Phase 3 safety study of
SAGE-718 in people with HD cognitive impairment.
- LIGHTWAVE (CNA-202) Study:
Initiate a placebo-controlled Phase 2 study of SAGE-718 in people
with mild cognitive impairment and mild dementia due to AD.
- Present additional SAGE-718 data throughout 2022.
Neurology Franchise
Sage’s neurology franchise features SAGE-324 and SAGE-689.
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 essential tremor (ET),
epilepsy and PD. SAGE-689 is an intramuscular GABAA receptor PAM in
development as a potential therapy for disorders associated with
acute GABA hypofunction.
Sage and its collaborator, Biogen, are currently enrolling
participants in the Phase 2b KINETIC 2 placebo-controlled study of
SAGE-324 in ET following positive results from the KINETIC Study.
The KINETIC 2 Study is a Phase 2b dose-ranging study with the
primary goal of defining the dose for SAGE-324 in ET with a good
tolerability profile and a dosing schedule to maintain plasma
concentrations needed for sustained tremor symptom control in
treating ET. Enrollment in the KINETIC 2 Study is now expected to
be completed in late 2023 due to a slower than anticipated pace of
enrollment.
Sage is also currently dosing patients in a Phase 2 long-term
open label safety study, to evaluate the long-term safety and
tolerability of SAGE-324 in ET. The primary endpoint is incidence
of treatment-emergent adverse events.
SAGE-689 continues in Phase 1 development.
Early Development
Sage is progressing its early development programs with
IND-enabling work underway for SAGE-319 and SAGE-421.
- SAGE-319: an oral, extrasynaptic GABAA receptor
preferring PAM that Sage plans to study for potential use in
disorders of social interaction.
- SAGE-421: an oral, NMDA receptor PAM that Sage plans to
study for potential use in neurodevelopmental disorders and
cognitive recovery and rehabilitation.
Business Updates
During the third quarter, Sage announced key leadership
changes:
- Laura Gault, M.D., Ph.D., joined Sage as Chief Medical
Officer. As a part of her new role, Laura will be focused on
advancing Sage’s current and emerging product pipeline through all
stages of development. Laura brings more than 15 years of
experience with an established track record of neuroscience drug
development and designing innovative clinical trial designs.
- Jeff Jonas, transitioning from his full-time role as
Chief Innovation Officer at Sage and will continue as a member of
the Board of Directors and other committees. Jeff will be pursuing
a new opportunity at a global private equity firm.
FINANCIAL RESULTS FOR THE THIRD QUARTER
2022
- Cash Position: Cash, cash equivalents and marketable
securities as of September 30, 2022 were $1.4 billion compared to
$1.5 billion at June 30, 2022.
- Revenue: Net revenue from sales of ZULRESSO was $1.7
million in the third quarter of 2022, compared to $1.4 million in
the same period of 2021.
- R&D Expenses: Research and development expenses were
$81.6 million, including $6.0 million of non-cash stock-based
compensation expense, in the third quarter of 2022 compared to
$83.5 million, including $17.9 million of non-cash stock-based
compensation expense, for the same period in 2021. The decrease in
R&D expenses was primarily due to the completion of the
WATERFALL Study and the CORAL Study for zuranolone and decreases in
non-cash stock-based compensation expense. Decreases were primarily
offset by increased spending on SAGE-324 and Sage’s wholly owned
pipeline, including SAGE-718 and other programs. The reimbursement
from Biogen for R&D expenses pursuant to the Sage/Biogen
Collaboration and License Agreement was $17.9 million in the third
quarter of 2022 compared to $21.6 million in the same period of
2021.
- SG&A Expenses: Selling, general and administrative
expenses were $61.5 million, including $7.2 million of non-cash
stock-based compensation expense, in the third quarter of 2022,
compared to $48.7 million, including $16.5 million of non-cash
stock-based compensation expense, for the same period in 2021. The
increase in SG&A expenses was primarily due to hiring employees
to support ongoing activities in anticipation of potential future
product launches of our product candidates. The reimbursement from
Biogen for SG&A expenses pursuant to the Sage/Biogen
Collaboration and License Agreement was $0.5 million in the third
quarter of 2022 compared to $2.6 million in the same period of
2021.
- Net Loss: Net loss was $137.3 million for the third
quarter of 2022 compared to $130.2 million for the same period of
2021.
FINANCIAL GUIDANCE
- Sage anticipates cash, cash equivalents and marketable
securities of approximately $1.3 billion at the end of 2022.
- The Company does not anticipate receipt of any milestone
payments from collaborations in 2022.
- The Company anticipates R&D and SG&A spending to
increase as it advances planned and ongoing studies for SAGE-718
and SAGE-324 and prepares for the potential launch of
zuranolone.
- The Company believes its cash and cash equivalents, anticipated
funding from ongoing collaborations, and potential revenue, will
support its operations into 2025.
Conference Call Information
Sage will host a conference call and webcast today, Tuesday,
November 8, at 8:00 a.m. ET to review its third quarter 2022
financial results and discuss recent corporate updates. The live
webcast can be accessed on the investor page of Sage's website at
investor.sagerx.com. A replay of the webcast will be available on
Sage's website following the completion of the event and will be
archived for up to 30 days.
About Sage Therapeutics
Sage Therapeutics is a biopharmaceutical company fearlessly
leading the way to create a world with better brain health. Our
mission is to pioneer solutions to deliver life-changing brain
health medicines, so every person can thrive. For more information,
please visit www.sagerx.com.
Forward-Looking Statements
Various statements in this release concern Sage's future
expectations, plans and prospects, including without limitation our
statements regarding: plans and potential timing for completion of
our rolling NDA submission for zuranolone in MDD and PPD; our
belief in the regulatory filing and review pathway for zuranolone
in MDD and PPD; the potential profile and benefit of zuranolone in
MDD and PPD; the potential for regulatory approval and commencement
of launch and commercialization of zuranolone; other planned next
steps for the zuranolone program; anticipated timelines for
commencement of trials, completion of dosing, initiation of new
activities and other plans for our other programs and early stage
pipeline; our belief in the potential profile and benefit of our
product candidates; potential indications for our product
candidates; the potential for success of our programs, and the
opportunity to help patients in various indications; the mission
and goals for our business; and our expectations with respect to
2022 year-end cash, no receipt of milestones from collaborations in
2022, funding of future operations and expectations for increases
in expenses. These statements constitute forward-looking statements
as that term is defined in the Private Securities Litigation Reform
Act of 1995. These forward-looking statements are neither promises
nor guarantees of future performance, and are subject to a variety
of risks and uncertainties, many of which are beyond our control,
which could cause actual results to differ materially from those
contemplated in these forward-looking statements, including the
risks that: we may experience delays or unexpected hurdles in our
efforts to complete our rolling NDA submission for zuranolone in
MDD and PPD and we may not be able to complete the submission on
the timeline we expect or at all; the FDA may find inadequacies and
deficiencies in our NDA for zuranolone, including in the data we
submit, despite prior discussions, and may decide not to accept the
NDA for filing; even if the FDA accepts the NDA for filing, the FDA
may find that the data included in the NDA are not sufficient for
approval and may not approve the NDA in MDD or PPD, or both; the
FDA may decide that the design, conduct or results of our completed
and ongoing clinical trials for zuranolone, even if positive, are
not sufficient for approval in MDD or PPD and may require
additional trials or data which may significantly delay and put at
risk our efforts to obtain approval and may not be successful; even
if our NDA is successfully filed and accepted, the FDA may not
grant priority review or meet expected review timelines for our
NDA; other decisions or actions of the FDA or other regulatory
agencies may affect our efforts with respect to zuranolone and our
plans, progress, results and expected timelines; results of ongoing
or future studies may impact our ability to obtain approval of
zuranolone or impair the potential profile of zuranolone; success
in earlier clinical trials of any of our other product candidates
may not be repeated or observed in ongoing or future studies, and
ongoing and future clinical trials may not meet their primary or
key secondary endpoints which may substantially impair development;
unexpected concerns may arise from additional data, analysis or
results from any of our completed studies; we may encounter adverse
events at any stage that negatively impact further development, the
potential for approval or the potential for successful
commercialization of any our product candidates or that require
additional nonclinical and clinical work which may not yield
positive results; we may encounter delays in initiation, conduct,
completion of enrollment or completion of our ongoing and planned
clinical trials, including as a result of slower than expected site
initiation, slower than expected enrollment, the need or decision
to expand the trials or other changes, that may impact our ability
to meet our expected timelines and increase our costs; decisions or
actions of the FDA or other regulatory agencies may affect the
initiation, timing, design, size, progress and cost of clinical
trials and our ability to proceed with further development or may
impair the potential for successful development; the anticipated
benefits of our ongoing collaborations, including the achievement
of events tied to milestone payments or the successful development
or commercialization of products and generation of revenue, may
never be achieved; the need to align with our collaborators may
hamper or delay our development and commercialization efforts or
increase our costs; our business may be adversely affected and our
costs may increase if any of our key collaborators fails to perform
its obligations or terminates our collaboration; the internal and
external costs required for our ongoing and planned activities, and
the resulting impact on expense and use of cash, may be higher than
expected which may cause us to use cash more quickly than we expect
or change or curtail some of our plans or both; we may never be
able to generate meaningful revenues from sales of ZULRESSO or to
generate revenues at levels we expect or at levels necessary to
justify our investment; we may not be successful in our efforts to
gain regulatory approval of products beyond ZULRESSO and, even if
successfully developed and approved, we may not achieve revenues
from such products, including zuranolone, if approved, at the
levels we expect; our expectations as to year-end cash and
sufficiency of cash to fund future operations and expense levels
may prove not to be correct for these and other reasons such as
changes in plans or actual events being different than our
assumptions; we may be opportunistic in our future financing plans
even if available cash is sufficient; additional funding may not be
available on acceptable terms when we need it; the number of
patients with the diseases or disorders for which our products are
developed, the unmet need for additional treatment options and the
potential market for our current or future products, including
zuranolone, if approved, may be significantly smaller than we
expect; ZULRESSO and zuranolone or any of our other products that
may be approved in the future may not achieve market acceptance or
we may encounter reimbursement-related or other market-related
issues that impact the success of our commercialization efforts;
and we may encounter technical and other unexpected hurdles in the
development and manufacture of our product candidates or the
commercialization of our marketed product which may delay our
timing or change our plans, increase our costs or otherwise
negatively impact our business; as well as those risks more fully
discussed in the section entitled "Risk Factors" in our most recent
quarterly report, as well as discussions of potential risks,
uncertainties, and other important factors in our subsequent
filings with the Securities and Exchange Commission. In addition,
any forward-looking statements represent our views only as of
today, and should not be relied upon as representing our views as
of any subsequent date. We explicitly disclaim any obligation to
update any forward-looking statements.
Financial Tables
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Statements of Operations (in thousands, except
share and per share data) (unaudited)
Three Months Ended
September 30, Nine Months Ended September 30,
2022
2021
2022
2021
Product revenue, net
$
1,739
$
1,440
$
4,821
$
4,666
Operating costs and expenses: Cost of goods sold
184
131
670
466
Research and development
81,553
83,497
236,868
207,723
Selling, general and administrative
61,482
48,706
160,370
131,899
Total operating costs and expenses
143,219
132,334
397,908
340,088
Loss from operations
(141,480)
(130,894)
(393,087)
(335,422)
Interest income, net
4,127
692
7,397
2,132
Other income, net
30
31
52
110
Net loss
$
(137,323)
$
(130,171)
$
(385,638)
$
(333,180)
Net loss per share - basic and diluted
$
(2.31)
$
(2.21)
$
(6.51)
$
(5.69)
Weighted average shares outstanding - basic and diluted
59,428,123
58,819,548
59,242,563
58,593,743
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Balance Sheets (in thousands) (unaudited)
September 30,2022 December 31,2021 Cash, cash
equivalents and marketable securities
$
1,393,639
$
1,742,296
Total assets
$
1,486,073
$
1,825,288
Total liabilities
$
105,951
$
96,257
Total stockholders' equity
$
1,380,122
$
1,729,031
ZULRESSO (brexanolone) SELECT IMPORTANT SAFETY
INFORMATION
This does not include all the information needed to use ZULRESSO
safely and effectively. See full prescribing information for
ZULRESSO.
WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF
CONSCIOUSNESS
See full prescribing information for complete boxed warning
Patients are at risk of excessive sedation or sudden loss of
consciousness during administration of ZULRESSO.
Because of the risk of serious harm, patients must be
monitored for excessive sedation and sudden loss of consciousness
and have continuous pulse oximetry monitoring. Patients must be
accompanied during interactions with their child(ren).
ZULRESSO is available only through a restricted program
called the ZULRESSO REMS.
WARNINGS AND PRECAUTIONS
Suicidal Thoughts and Behaviors: Consider changing the
therapeutic regimen, including discontinuing ZULRESSO, in patients
whose PPD becomes worse or who experience emergent suicidal
thoughts and behavior.
ADVERSE REACTIONS: Most common adverse reactions
(incidence ≥5% and at least twice the rate of placebo) were
sedation/somnolence, dry mouth, loss of consciousness, and
flushing/hot flush.
USE IN SPECIFIC POPULATIONS
• Pregnancy: ZULRESSO may cause fetal harm. Healthcare
providers are encouraged to register patients by calling the
National Pregnancy Registry for Antidepressants at 1-844-405-6185
or visiting online at
https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/
• Renal Impairment: Avoid use of ZULRESSO in patients
with end stage renal disease (ESRD)
Controlled Substance: ZULRESSO contains brexanolone, a
Schedule IV controlled substance under the Controlled Substances
Act.
To report SUSPECTED ADVERSE REACTIONS, contact Sage
Therapeutics, Inc. at 1-844-4-SAGERX (1-844-472-4379) or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
Please see accompanying full Prescribing Information
including Boxed Warning.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20221108005333/en/
Investors Helen Rubinstein 315-382-3979
helen.rubinstein@sagerx.com
Media Matthew Henson 917-930-7147
matthew.henson@sagerx.com
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