Rolling NDA submission for zuranolone in MDD
underway, with full submission expected to be completed in the
second half of 2022, associated NDA submission in PPD planned for
early 2023
Topline data from Phase 3 SKYLARK Study
evaluating 50 mg zuranolone for PPD on track for mid-2022
Six planned and ongoing Phase 2 studies across
neuropsychiatry and neurology franchises, demonstrate focused
execution across pipeline programs
Company leadership strengthened with
appointment of Mark Pollack, M.D., as Senior Vice President,
Medical Affairs
Conference call today at 8:00 a.m. ET
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
first quarter ended March 31, 2022.
“Current events have put a spotlight on the need for significant
progress in brain health disorders, and at Sage, we’ve made a
strong start to 2022 with the initiation of our rolling regulatory
submission for zuranolone in major depressive disorder and
meaningful progress across our entire pipeline,” said Barry Greene,
Chief Executive Officer at Sage Therapeutics. “We are currently
executing four Phase 2 studies across our neuropsychiatry and
neurology franchises, and we recently presented encouraging data
from our SAGE-718 program in patients with mild cognitive
impairment due to Parkinson’s disease and mild cognitive impairment
and mild dementia due to Alzheimer’s disease at key scientific
forums. Most importantly, across our programs we remain focused on
innovation that emphasizes outcomes that are most important to
patients, as we progress our mission to pioneer solutions to
deliver life-changing brain health medicines, so every person can
thrive.”
First 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 intended 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 major depressive disorder (MDD) and postpartum
depression (PPD), and ZULRESSO® (brexanolone) CIV injection,
approved by the U.S. Food and Drug Association (FDA) as the first
treatment specifically indicated for PPD. Zuranolone has received
Breakthrough Therapy Designation for the treatment of MDD and Fast
Track Designation for the treatment of PPD from the FDA.
Zuranolone is being evaluated, in collaboration with Biogen, as
a potential rapid-acting, oral, once-daily, two-week treatment for
MDD and PPD in the LANDSCAPE and NEST clinical development
programs, respectively. The LANDSCAPE and NEST programs include
five positive clinical trials in people with MDD and PPD, as well
as the ongoing SKYLARK Study. Additionally, Shionogi completed a
positive Phase 2 study with zuranolone in MDD. In the first quarter
of this year, Sage and Biogen announced that the CORAL Study met
the study objectives. In meeting its pre-defined objectives, the
CORAL Study supports the potential of zuranolone, when co-initiated
with standard of care, to accelerate the benefit of depression
treatment compared to treatment with antidepressant treatments
(ADTs) alone.
Yesterday, Sage and Biogen announced the initiation of a rolling
New Drug Application (NDA) submission to the FDA for zuranolone in
MDD with plans to complete the submission in the second half of
2022. An associated NDA filing for PPD is anticipated in early 2023
pending results from the SKYLARK Study.
The Company expects to achieve the following milestones across
its depression franchise in 2022, with plans to share additional
analyses from completed and ongoing studies at scientific forums
throughout the year:
- Mid-2022:
- SKYLARK (PPD-301) Study: Report
topline data from the placebo-controlled Phase 3 study evaluating a
two-week course of zuranolone 50 mg in women with PPD, with
additional short-term follow-up.
- Late 2022:
- Complete rolling NDA submission for zuranolone in MDD (2H
2022).
- Announce topline data from the SUNBIRD Study, designed to
evaluate the safe-use administration of ZULRESSO for the treatment
of PPD in a patient’s home (late 2022).
- Present further zuranolone data, including analyses from the
SHORELINE Study in MDD.
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 of SAGE-718 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 a Phase 2 study in people with MCI and mild dementia due to
AD.
- DIMENSION (CIH-201) Study: Sage is
currently enrolling the Phase 2 DIMENSION Study, a double-blind,
placebo-controlled study in patients with HD cognitive impairment.
The study is designed to evaluate the efficacy of once-daily dosed
SAGE-718 over three months, with a target enrollment of
approximately 178 patients. Sage expects the DIMENSION Study to
include more than 40 clinical sites.
- SURVEYOR (CIH-202) Study: The
SURVEYOR Study is a placebo-controlled Phase 2 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
Phase 2 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 patients with MCI due to PD over
42 days, followed by a controlled follow-up period.
Additionally, the Company recently presented data from completed
SAGE-718 studies in PD and AD cognitive impairment at key
scientific forums. Data from the Company’s Phase 2 open label
PARADIGM Study presented at the AD/PD 2022 Advances in Science
& Therapy International Conference on Alzheimer’s and
Parkinson’s Diseases and Related Neurological Disorders, showed
that SAGE-718 given once daily for 14 days was associated with
improvements in executive function and learning and memory at Day
14 in patients with MCI due to PD. Additionally, sustained effects
and improving trends were seen out to Day 28. Data from the Phase 2
open-label LUMINARY Study in individuals with MCI and mild dementia
due to AD presented at the American Academy of Neurology showed
that SAGE-718 given once daily for 14 days was generally
well-tolerated and associated with improved executive performance
and learning and memory. At Day 14, improvements from baseline were
observed in multiple tests of executive functioning and learning
and memory. Statistically significant improvement was also observed
in the Montreal Cognitive Assessment at Day 28.
The Company expects to achieve the following milestones across
its neuropsychiatry franchise in 2022:
- Late 2022:
- Phase 2/3 Study in HD (CIH-301):
Initiate a Phase 2/3 open-label extension study of SAGE-718 in
people with HD cognitive impairment.
- Phase 2 Study in AD (CNA-202):
Initiate a placebo-controlled Phase 2 study of SAGE-718 in people
with MCI and mild dementia due to AD.
Sage also plans to share additional analyses from studies
completed with SAGE-718 to date 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
people 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 and frequency 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.
Sage also plans to initiate a Phase 2 long-term open label
safety study with SAGE-324. The study is designed to evaluate the
long-term safety and tolerability of SAGE-324 in ET, with incidence
of treatment-emergent adverse events as the primary endpoint.
SAGE-689 continues in Phase 1 development.
The Company expects to achieve the following milestones across
its neurology franchise in 2022:
- Mid-2022:
- Initiate a Phase 2 safety study with SAGE-324 in ET.
- Late 2022:
- Complete enrollment in KINETIC 2 Study of SAGE-324 in ET.
Sage also plans to share additional analyses from studies
completed with SAGE-324 to date throughout 2022.
Early Development Sage is progressing its early
development programs with IND-enabling studies 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 Sage announced today that Mark Pollack,
M.D., joined the Company as Senior Vice President, Medical Affairs.
Dr. Pollack will lead Sage’s global medical affairs efforts across
all Sage programs, with a focus on supporting the Company’s
external relationships with the scientific community. Dr. Pollack
joins Sage from Myriad Genetics, where he served as Chief Medical
Officer of the Neuroscience Business Unit. Additionally, Dr.
Pollack brings 35 years of proven leadership in scientific research
and medical practice, including positions as Chair of the
Department of Psychiatry and Behavioral Sciences at Rush University
Medical Center, Professor of Psychiatry at Massachusetts General
Hospital and Harvard Medical School.
ANTICIPATED 2022
MILESTONES
- Zuranolone:
- Report topline data from the SKYLARK Study in PPD
(mid-2022).
- Complete NDA submission in MDD (2H 2022).
- Present further zuranolone data, including analyses from the
SHORELINE Study in MDD.
- SAGE-718:
- Initiate Phase 2/3 HD cognitive impairment open label extension
study (late 2022).
- Initiate placebo-controlled Phase 2 Study in people with mild
cognitive impairment and mild dementia due to AD (late 2022).
- SAGE-324:
- Initiate Phase 2 safety study in ET (mid-2022).
- ZULRESSO:
- Announce topline data from the SUNBIRD Study, designed to
evaluate the safe-use administration of ZULRESSO for the treatment
of PPD in a patient’s home (late 2022).
FINANCIAL RESULTS FOR THE FIRST QUARTER
2022
- Cash Position: Cash, cash equivalents and marketable
securities as of March 31, 2022 were $1.6 billion compared to $1.7
billion at December 31, 2021.
- Revenue: Net revenue from sales of ZULRESSO was $1.6
million in the first quarter of 2022 and in the same period of
2021.
- R&D Expenses: Research and development expenses were
$78.0 million, including $8.6 million of non-cash stock-based
compensation expense, in the first quarter of 2022 compared to
$58.1 million, including $9.3 million of non-cash stock-based
compensation expense, in the same period of 2021, an increase of
$19.9 million. The increase in spending was primarily due to
increased spending on SAGE-324 and Sage’s wholly owned pipeline
including SAGE-718 and other programs, partially offset by
decreased spending on zuranolone, primarily due to completion of
the WATERFALL Study and the CORAL Study. The reimbursement from
Biogen pursuant to the Sage/Biogen Collaboration and License
Agreement was $18.5 million in the first quarter of 2022 compared
to $22.1 million in the same period of 2021.
- SG&A Expenses: Selling, general and administrative
expenses were $46.5 million, including $9.9 million of non-cash
stock-based compensation expense, in the first quarter of 2022
compared to $39.8 million, including $12.7 million of non-cash
stock-based compensation expense, in the same period of 2021, an
increase of $6.7 million. The increase was primarily related to
hiring employees to support ongoing activities in anticipation of
potential future launches of our product candidates. The
reimbursement from Biogen pursuant to the Sage/Biogen Collaboration
and License Agreement was $1.5 million in the first quarter of 2022
compared to $2.7 million in the same period of 2021.
- Net Loss: Net loss was $122.1 million in the first
quarter of 2022 compared to $95.8 million in 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 believes its cash and cash equivalents, anticipated
funding from our ongoing collaborations, and potential revenue,
will support its operations into 2025.
Conference Call Information Sage will host a conference
call and webcast today, Tuesday, May 3, at 8:00 a.m. ET to discuss
its first quarter 2022 financial results and 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 approximately two hours after 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 for
completion of our rolling NDA filing for zuranolone in MDD and
associated submission for zuranolone in PPD, and the potential
timing of such activities; our belief in the regulatory filing
pathways for zuranolone; the potential profile and benefit of
zuranolone in MDD and PPD; the potential for regulatory approval
and commencement of commercialization of zuranolone; other planned
next steps for the program; anticipated timelines for reporting
clinical trial results, commencement of trials, and initiation of
new activities; our plans for advancement of our 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 and funding of
future operations. 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 our planned submission in PPD
and we may not be able to complete the submissions on the timelines
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; 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 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 or results; we may experience negative results in
the ongoing SKYLARK Study in PPD that negatively affect our ability
to file an NDA for approval of zuranolone in PPD; 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 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 of development that negatively impact further
development or that require additional nonclinical and clinical
work which may not yield positive results; we may encounter delays
in initiation, conduct or completion of our ongoing and planned
clinical trials, including as a result of slower than expected site
initiation or 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 at the levels we expect; our expectations as to
year-end cash and sufficiency of cash to fund future operations 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 may be
significantly smaller than we expect; any of our 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
annual/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 March
31,
2022
2021
Product revenue, net
$
1,582
$
1,583
Operating costs and expenses: Cost of goods sold
286
187
Research and development
78,018
58,056
Selling, general and administrative
46,477
39,847
Total operating costs and expenses
124,781
98,090
Loss from operations
(123,199
)
(96,507
)
Interest income, net
1,168
708
Other income (expense), net
(24
)
35
Net loss
$
(122,055
)
$
(95,764
)
Net loss per share - basic and diluted
$
(2.07
)
$
(1.64
)
Weighted average shares outstanding - basic and diluted
59,028,858
58,374,219
Sage Therapeutics, Inc. and
Subsidiaries
Condensed Consolidated Balance
Sheets
(in thousands)
(unaudited)
March 31, 2022
December 31, 2021
Cash, cash equivalents and marketable securities
$
1,625,241
$
1,742,296
Total assets
$
1,705,703
$
1,825,288
Total liabilities
$
87,201
$
96,257
Total stockholders' equity
$
1,618,502
$
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/20220502005915/en/
Investor Contact Helen Rubinstein 315-382-3979
helen.rubinstein@sagerx.com
Media Contact Becky Kern 914-772-2310
becky.kern@sagerx.com
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