Rolling NDA submission for zuranolone in MDD
and PPD remains on track, with completion expected in the second
half of 2022
Announced positive topline data from the Phase
3 SKYLARK Study evaluating 50 mg zuranolone for PPD
Enrolling multiple Phase 2 studies across
neuropsychiatry and neurology franchises, additional trials
expected to initiate throughout 2022
Cash and cash equivalents, anticipated funding
from ongoing collaborations, and potential revenue, expected to
support operations into 2025
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
second quarter ended June 30, 2022.
“The first half of 2022 has been marked by important clinical
and regulatory achievements across our entire pipeline, paving the
way for continued focused execution throughout the remainder of the
year,” said Barry Greene, Chief Executive Officer at Sage
Therapeutics. “We are making progress on the NDA submission for
zuranolone and building our organization to support a potential
launch. Based on the consistent clinical profile of zuranolone, we
believe it has the potential, if approved, to address the
significant unmet need for people suffering from MDD and PPD and we
are working with a sense of urgency toward our goal of bringing
zuranolone to them. Beyond zuranolone, we are continuing to advance
our pipeline, with the presentation of multiple data sets at key
upcoming scientific congresses. I believe our progress this year,
combined with the strong foundation we’ve built, supports our
growth as a leader in brain health and a top-tier biopharmaceutical
company.”
Second 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 second quarter of this year, Sage and its
collaborator, Biogen, announced that the SKYLARK Study of
zuranolone in PPD met its primary and all key secondary
endpoints.
In June 2022, Sage and Biogen announced that the rolling NDA
submission that was previously initiated will seek approval for
both MDD and PPD in one filing. The Companies plan to complete
submission of the single NDA for zuranolone for the treatment of
both MDD and PPD to the FDA in the second half of this year,
accelerating previously planned timelines for PPD.
The Company also shared insights from the terminated RAINFOREST
and REDWOOD Studies today. The RAINFOREST Study was designed to
investigate the efficacy and safety of 30 mg zuranolone in comorbid
MDD and insomnia. The REDWOOD Study was designed to study fixed
schedule intermittent dosing of 30 mg zuranolone throughout the
course of a year. Both studies were terminated in 2020 based on the
Company’s plans to advance the program with the 50 mg dose of
zuranolone.
The RAINFOREST Study, which enrolled 87 patients, was terminated
prior to achieving the planned sample size. As the study was not
fully enrolled, the statistical analysis plan was invalid. The
study directionality showed that zuranolone may benefit sleep
efficiency, with numerical improvement in objective measures of
quality of sleep, including wake after sleep onset, total sleep
time, latency to persistent sleep, median number of awakenings, and
mean duration of awakenings, and differences on endpoints involving
REM sleep. The REDWOOD Study did not enroll enough patients for
efficacy analyses to be performed. There were no new safety
findings from the study. In the open-label SHORELINE Study, a large
naturalistic study in the zuranolone development program, 80% of
patients who responded to initial treatment with zuranolone 50 mg
received only 1 or 2 treatment courses during their time in the
year-long study, with a median time to the second treatment course
of 249 days also with no new safety findings.
Additionally, Sage today announced that the SUNBIRD Study
evaluating the safe-use administration of ZULRESSO as a treatment
for PPD in a woman’s home has completed enrollment. Sage does not
plan any label changes from this study.
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 (2H
2022).
- Present additional 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 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 people 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 people. 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 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 Study in HD (CIH-301):
Initiate a Phase 3 safety 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 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
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 recently initiated a Phase 2 long-term open label
safety study with SAGE-324, 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:
- Late 2022:
- Complete enrollment in KINETIC 2 Study of SAGE-324 in ET.
- Present additional SAGE-324 data throughout 2022.
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.
FINANCIAL RESULTS FOR THE SECOND
QUARTER 2022
- Cash Position: Cash, cash equivalents and marketable
securities as of June 30, 2022 were $1.5 billion compared to $1.6
billion at March 31, 2022.
- Revenue: Net revenue from sales of ZULRESSO was $1.5
million in the second quarter of 2022, compared to $1.6 million in
the same period of 2021.
- R&D Expenses: Research and development expenses were
$77.3 million, including $6.5 million of non-cash stock-based
compensation expense, in the second quarter of 2022 compared to
$66.2 million, including $13.5 million of non-cash stock-based
compensation expense, for the same period in 2021. The increase in
R&D expenses was primarily due to increased spending on
SAGE-324 and Sage’s wholly owned pipeline, including SAGE-718 and
other programs. The reimbursement from Biogen pursuant to the
Sage/Biogen Collaboration and License Agreement was $21.0 million
in the second quarter of 2022 compared to $20.1 million in the same
period of 2021.
- SG&A Expenses: Selling, general and administrative
expenses were $52.4 million, including $8.2 million of non-cash
stock-based compensation expense, in the second quarter of 2022,
compared to $43.3 million, including $14.2 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 pursuant to the Sage/Biogen Collaboration and License
Agreement was $2.8 million in the second quarter of 2022 compared
to $3.5 million in the same period of 2021.
- Net Loss: Net loss was $126.3 million for the second
quarter of 2022 compared to $107.2 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, August 2, at 8:00 a.m. ET to
discuss its second 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 and
potential timing for completion of our rolling NDA submission for
zuranolone in MDD and PPD; our belief in the regulatory filing
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 commercialization of zuranolone; other
planned next steps for the zuranolone program; anticipated
timelines for commencement of trials, 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; 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; 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 that negatively impact further development, the
potential for approval or the potential for successful
commercialization 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 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 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
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 June
30,
Six Months Ended June
30,
2022
2021
2022
2021
Product revenue, net
$
1,501
$
1,643
$
3,082
$
3,226
Operating costs
and expenses: Cost of
goods sold
200
148
486
335
Research and development
77,297
66,170
155,315
124,226
Selling, general and administrative
52,411
43,346
98,888
83,193
Total operating costs and expenses
129,908
109,664
254,689
207,754
Loss from operations
(128,407
)
(108,021
)
(251,607
)
(204,528
)
Interest income,
net
2,102
732
3,270
1,440
Other income, net
45
44
22
79
Net loss
$
(126,260
)
$
(107,245
)
$
(248,315
)
$
(203,009
)
Net loss per share - basic and diluted
$
(2.13
)
$
(1.83
)
$
(4.20
)
$
(3.47
)
Weighted average shares outstanding - basic and diluted
59,266,322
58,582,569
59,148,246
58,478,970
Sage Therapeutics, Inc. and Subsidiaries
Condensed Consolidated Balance Sheets (in thousands)
(unaudited)
June 30,2022
December 31,2021 Cash, cash equivalents and
marketable securities
$
1,513,707
$
1,742,296
Total assets
$
1,601,377
$
1,825,288
Total liabilities
$
97,141
$
96,257
Total stockholders' equity
$
1,504,236
$
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/20220801005685/en/
Investors Helen Rubinstein 315-382-3979
helen.rubinstein@sagerx.com
Media Becky Kern 914-772-2310 becky.kern@sagerx.com
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