Announced positive topline data from pivotal
WATERFALL Study of zuranolone in patients with MDD showing
statistically significant and clinically meaningful reduction in
depressive symptoms at Day 15, primary endpoint
Continued pipeline expansion and acceleration
advancing all three brain health franchises, including first
patient dosed in SAGE-718 PARADIGM Parkinson’s disease Study Part B
and initiation of Phase 1 program for SAGE-689
Updated enrollment guidance for Phase 3 SKYLARK
Study of zuranolone in women with PPD with topline data now
expected mid-2022
Company announces REDWOOD and RAINFOREST
Studies not expected to be required for a potential zuranolone NDA
submission
Conference call today at 8:00 a.m. ET
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,
2021.
“Sage has made incredible progress on our mission to become the
leader in brain health in the first half of 2021, setting us up for
multiple near-mid and long-term catalysts,” said Barry Greene,
chief executive officer, Sage Therapeutics. “Our goal of making
medicines that matter for people with brain health disorders is
more important than ever, and we are committed to delivering
innovative therapies. The LANDSCAPE and NEST programs for
zuranolone are examples of Sage’s unique approach to designing
integrated clinical development strategies that we believe will
enable us to bring paradigm shifting treatments to market and
address the greatest unmet needs for patients. I look forward to
providing further updates on zuranolone and the rest of Sage’s
robust pipeline in the second half of the year.”
Second Quarter 2021 and Recent
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 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 major depressive
disorder (MDD).
Zuranolone is being evaluating as a potential rapid-acting,
durable, two-week treatment for PPD and MDD in the NEST and
LANDSCAPE clinical trial programs.
Sage and Biogen, its collaborator on zuranolone and SAGE-324,
recently announced that the WATERFALL Study, a pivotal, Phase 3,
double-blind, randomized, placebo-controlled study evaluating the
efficacy and safety of zuranolone 50 mg in adults 18 to 64 years
with MDD, met its primary endpoint demonstrating statistically
significant and clinically meaningful improvement in depressive
symptoms compared with placebo at Day 15 as assessed by the 17-item
Hamilton Rating Scale for Depression (HAMD-17) total score.
- The WATERFALL Study enrolled 543 patients with MDD; patients
were treated with zuranolone 50 mg or placebo once nightly for 14
days.
- The mean (SD) baseline HAMD-17 score at entry into the study
was 26.8 (2.60) in the zuranolone 50 mg treatment group (n=268) and
26.9 (2.67) in the placebo group (n=269).
- 90.3% of patients who received zuranolone, and 87.4% of
patients who received placebo, completed the study.
- The LS means (SE) change from baseline in HAMD-17 total score
at Day 15 for patients who received zuranolone 50 mg was -14.1
(0.51) compared with -12.3 (0.50) for patients who received placebo
(LS mean difference -1.7 points; p=0.0141).
- Rapid and significant onset of treatment effect was also seen
in HAMD-17 results at Days 3, 8, and 12.
- Patients with a response to zuranolone at Day 15 retained on
average 86% of their HAMD-17 improvement at Day 42 (4 weeks after
dosing ended).
- Zuranolone was generally well-tolerated in the WATERFALL Study
and demonstrated a safety profile consistent with previous clinical
studies. The most common treatment-emergent adverse events (TEAEs)
that were ≥ 5% in patients treated with zuranolone (rates vs
placebo) included somnolence 15.3% (vs 3.0%), dizziness 13.8% (vs
2.2%), headache 10.8% (vs 7.8%), and sedation 7.5% (vs 0.4%); these
events predominantly occurred during the 14-day treatment period.
- There were no reports of weight gain, sexual dysfunction,
euphoria or nausea typically associated with most, if not all,
antidepressant drugs
Zuranolone has been granted Breakthrough Therapy Designation by
the FDA, and Sage and Biogen plan to discuss next steps with the
Agency. Additional analysis and full data from the WATERFALL Study
will be shared at future scientific forums.
Additionally, the Company is formally terminating the REDWOOD
and RAINFOREST Studies, which were suspended in the first quarter
of 2020. After discussions with the FDA, Sage does not believe that
these studies will be required for a potential NDA submission.
The Company expects the following zuranolone data readouts in
2021 and 2022:
- Late 2021:
- CORAL (MDD-305) Study: A
placebo-controlled Phase 3 trial evaluating a two-week course of
zuranolone 50 mg, when co-initiated with a new antidepressant, in
patients with MDD, with additional short-term follow-up.
- SHORELINE (MDD-303) Study 50 mg Cohort
(1-year data cut): An open-label Phase 3 trial designed to
naturalistically follow patients with MDD and evaluate the safety
and tolerability of zuranolone 50 mg in adults for up to one year.
The Company announced interim data from the 50 mg treatment cohort
in March 2021.
- Mid-2022:
- SKYLARK (PPD-301) Study: A
placebo-controlled Phase 3 trial evaluating a two-week course of
zuranolone 50 mg in women with PPD, with additional short-term
follow-up.
- Sage now expects topline data for the SKYLARK Study in
mid-2022, because of a slower than anticipated pace of enrollment
in the study, due to a lower number of women seeking care for PPD
and a lower rate of childbirth during the pandemic.
Sage today announced topline data from the Phase 3 CHICKADEE
Study evaluating the safety of ZULRESSO treatment in adolescent
females aged 15 to 17 with postpartum depression. This study was
conducted as a post-marketing requirement to investigate ZULRESSO
in an adolescent population diagnosed with PPD. In the study, the
safety and pharmacokinetic profile of ZULRESSO in this population
was consistent with prior studies in adults and the FDA-approved
product label. While not the primary endpoint, efficacy results
were positive and consistent with previous studies.
Neurology Franchise
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 Parkinson’s disease (PD).
In the second quarter, Sage and Biogen announced that the
KINETIC Study, a Phase 2 multicenter, randomized, double-blind,
placebo-controlled study of SAGE-324 in ET, met its primary
endpoint.
- In the study, SAGE-324 demonstrated a statistically significant
reduction from baseline in the TETRAS Item 4 upper limb tremor
score at Day 29 in the total studied population compared to
placebo.
- Also in the study, SAGE-324 demonstrated a statistically
significant correlation between TETRAS tremor score and activities
of daily living at all measured time points.
- Sage and Biogen anticipate initiating a Phase 2 dose-ranging
study in late 2021, with the goal of optimizing the dose and
frequency, including to maintain plasma concentrations that
translate into sustained tremor symptom control.
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).
This quarter, Sage dosed the first patient in the 4-week dosing
cohort, or part B, of the PARADIGM Study to gather additional data
on SAGE-718 in the PD patient population. The PARADIGM study is a
Phase 2a open-label study in patients aged 50 to 75 years old with
mild cognitive impairment due to PD. Additionally, the LUMINARY
Study, a Phase 2a open-label trial evaluating SAGE-718 in patients
with AD mild cognitive impairment and mild dementia is ongoing.
The following milestones are expected for the neuropsychiatry
franchise in 2021:
- Late 2021:
- LUMINARY (718-CNA-201)
Study: The Company anticipates topline data from the
LUMINARY Study in late 2021.
- Phase 2 Study in HD: The Company
expects to initiate a placebo-controlled Phase 2 trial with
SAGE-718 in early to moderate HD in late 2021.
Early Development
Sage expects to complete certain ongoing Phase 1 clinical
studies for two programs in its early development pipeline in late
2021, SAGE-689 (single ascending dose) and SAGE-904 (single
ascending dose and multiple ascending dose). Results from the Phase
1 studies will inform further development of these programs.
- SAGE-689: an intramuscular GABAA receptor PAM in
development as a potential therapy for disorders associated with
acute GABA hypofunction. In the second quarter, the first patient
was dosed in the SAGE-689 Phase 1 SAD study.
- SAGE-904: Sage’s second NMDA receptor PAM product
candidate in development as a potential oral therapy for disorders
associated with NMDA hypofunction. In the second quarter, the first
patient was dosed in the continued SAGE-904 Phase 1 studies.
Additionally, IND-enabling work is underway for SAGE-319.
- SAGE-319: an oral, extrasynaptic GABAA receptor
preferring PAM that Sage plans to study for potential use in
disorders of social interaction.
The Company plans to advance SAGE-421 to preclinical
studies.
- SAGE-421: an oral, NMDA receptor PAM that Sage plans to
study for potential use in neurodevelopmental disorders and
cognitive recovery and rehabilitation.
Other Development Opportunities
Sage’s Phase 3 trial with brexanolone in ventilated intensive
care unit patients with advanced COVID-19 related acute respiratory
distress syndrome (ARDS) did not meet enrollment expectations and
was closed to enrollment this quarter. Sage has terminated the
study.
ANTICIPATED 2021
MILESTONES
Late 2021:
- Zuranolone:
- Report topline data from Phase 3 CORAL Study
- Report topline data cut from Phase 3 SHORELINE Study 50 mg
cohort
- SAGE-324:
- Initiate Phase 2 dose-ranging study in ET
- SAGE-718:
- Report topline data from Phase 2a LUMINARY open-label, signal
finding study in patients with AD mild cognitive impairment and
mild dementia
- Initiate placebo-controlled Phase 2 study in early to moderate
HD
- SAGE-689 & SAGE-904:
- Complete ongoing Phase 1 studies (SAD for SAGE-689 and SAD/MAD
for SAGE-904)
FINANCIAL RESULTS FOR THE SECOND
QUARTER 2021
- Cash Position: Cash, cash equivalents and marketable
securities as of June 30, 2021 were $1.9 billion compared to $2.0
billion at March 31, 2021.
- Revenue: Net revenue from sales of ZULRESSO was $1.6
million in the second quarter of 2021 compared to $1.1 million in
the same period of 2020.
- R&D Expenses: Research and development expenses were
$66.2 million, including $13.5 million of non-cash stock-based
compensation expense, in the second quarter of 2021 compared to
$73.3 million, including $10.1 million of non-cash stock-based
compensation expense, for the same period in 2020, a decrease of
$7.1 million. The amount for the second quarter of 2021 reflects an
increase in expenses of $13.0 million and a reduction in expenses
of $20.1 million due to reimbursement from Biogen pursuant to the
Sage/Biogen Collaboration and License Agreement. The primary
reasons for the increase in expenses were clinical pharmacology
studies that began in 2021 and non-cash stock-based compensation
expense from the achievement of a milestone for certain outstanding
performance restricted stock units.
- SG&A Expenses: Selling, general and administrative
expenses were $43.3 million, including $14.2 million of non-cash
stock-based compensation expense, in the second quarter of 2021
compared to $38.2 million, including $12.1 million of non-cash
stock-based compensation expense, for the same period in 2020, an
increase of $5.1 million. The amount for the second quarter of 2021
reflects an increase in expenses of $8.6 million and a reduction in
expenses of $3.5 million due to reimbursement from Biogen pursuant
to the Sage/Biogen Collaboration and License Agreement. The primary
reasons for the increase in expenses were an increase in activities
focused on disease awareness, increased launch readiness activities
for a potential product launch, if our zuranolone development
efforts are successful, and non-cash stock-based compensation
expense from the achievement of a milestone for certain outstanding
performance restricted stock units.
- Restructuring Expenses: Sage had no restructuring
expenses in the second quarter of 2021 compared to $28.4 million in
the second quarter of 2020.
- Net Loss: Net loss was $107.2 million for the second
quarter of 2021 compared to a net loss of $136.3 million for the
same period in 2020.
FINANCIAL GUIDANCE
- Sage anticipates cash, cash equivalents, and marketable
securities of more than $1.7 billion at end of 2021.
- The Company does not anticipate receipt of any milestone
payments from collaborations in 2021.
Conference Call Information
Sage will host a conference call and webcast today, Tuesday,
August 3, at 8:00 am ET to discuss its second quarter 2021
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 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.
Forward-Looking
Statements
Various statements in this release concern Sage's future
expectations, plans and prospects, including without limitation:
our views and expectations regarding our planned research and
development activities and related timelines, including 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, the potential for our programs, and the
opportunity to help patients in various indications; our belief and
expectations as to the potential regulatory pathways and
requirements for filing a potential new drug application for
zuranolone and for possible approval; potential indications for our
product candidates; the mission and goals for our business and
potential value creation opportunities; and our expectations with
respect to 2021 year-end cash. 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:
success in non-clinical studies or in earlier clinical trials or at
interim time periods may not be repeated or observed in ongoing or
future studies, and ongoing and future non-clinical and clinical
results may not meet their primary or key secondary endpoints or be
sufficient to file for or gain regulatory approval to market the
product without further development work or may not support further
development at all; 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; the
impact of the COVID-19 pandemic on our clinical development efforts
may be more significant than we expect if new surges continue; the
FDA may ultimately decide that the design or results of our
completed, ongoing and planned clinical trials for zuranolone or
any of our other product candidates, even if positive, are not
sufficient to file for or obtain regulatory approval in the
indications that are the focus of our development plans even if we
have had prior discussions with the agency supporting our approach;
other 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; the anticipated benefits of our ongoing collaborations
may never be achieved and 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 development of any of our product candidates in
any indication we are currently pursuing or may in the future
pursue; our expectations as to year-end cash may prove not to be
correct for 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; 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 on Form 10-Q, 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.
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,
2021
2020
2021
2020
Product revenue, net
$
1,643
$
1,089
$
3,226
$
3,375
Operating costs and expenses: Cost of goods sold
148
110
335
280
Research and development
66,170
73,320
124,226
136,930
Selling, general and administrative
43,346
38,224
83,193
108,355
Restructuring
-
28,402
-
28,402
Total operating costs and expenses
109,664
140,056
207,754
273,967
Loss from operations
(108,021
)
(138,967
)
(204,528
)
(270,592
)
Interest income, net
732
2,686
1,440
7,416
Other income (expense), net
44
(66
)
79
89
Net loss
$
(107,245
)
$
(136,347
)
$
(203,009
)
$
(263,087
)
Net loss per share - basic and diluted
$
(1.83
)
$
(2.63
)
$
(3.47
)
$
(5.07
)
Weighted average shares outstanding - basic and diluted
58,582,569
51,926,074
58,478,970
51,917,417
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Balance Sheets (in thousands) (unaudited)
June 30,2021 December 31,2020 Cash, cash equivalents
and marketable securities
$
1,911,315
$
2,099,549
Total assets
$
2,015,475
$
2,159,246
Total liabilities
$
85,963
$
86,912
Total stockholders' equity
$
1,929,512
$
2,072,334
ZULRESSO can cause serious side effects, including:
- Excessive sedation and sudden loss of consciousness.
ZULRESSO may cause you to feel very sleepy (excessive sedation) or
pass out (loss of consciousness). Your healthcare provider should
check you for symptoms of excessive sleepiness every 2 hours while
you are awake.
- During your infusion, tell your healthcare provider right away
if you feel like you cannot stay awake during the time you are
normally awake or if you feel like you are going to pass out. Your
healthcare provider may lower your dose or stop the infusion until
symptoms go away.
- You must have a caregiver or family member with you to help
care for your child(ren) during your infusion.
- Because of the risk of serious harm resulting from excessive
sedation or sudden loss of consciousness, ZULRESSO is only
available through a restricted program called the ZULRESSO
REMS.
ZULRESSO can cause other serious side effects,
including:
- Increased risk of suicidal thoughts or actions. ZULRESSO
and other antidepressant medicines may increase suicidal thoughts
and actions in some people 24 years of age and younger. Pay
close attention to and tell your healthcare provider right away if
you have any of the following symptoms, especially if they are new,
worse, or worry you:
- Attempts to commit suicide, thoughts about suicide or dying,
new or worse depression, other unusual or sudden changes in
behavior or mood.
- Keep all follow-up visits and call your healthcare provider
between visits as needed, especially if you have concerns about
symptoms.
The most common side effects of ZULRESSO include:
- Sleepiness, dry mouth, passing out, flushing of the skin or
face.
Call your doctor for medical advice about side effects. You may
report side effects to FDA at 1-800-FDA-1088.
Before receiving ZULRESSO, tell your healthcare provider
about all your medical conditions including if you drink
alcohol, have kidney problems, are pregnant or think you may be
pregnant, or are breastfeeding or plan to breastfeed. It is not
known if ZULRESSO will harm your unborn baby. If you become
pregnant during treatment, talk with your healthcare provider about
enrolling with the National Pregnancy Registry for Antidepressants
at 1-844-405-6185.
While receiving ZULRESSO, avoid the following:
- Driving a car or doing other dangerous activities after your
ZULRESSO infusion until your feeling of sleepiness has completely
gone away.
- Do not drink alcohol.
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. ZULRESSO and some medicines may
interact with each other and cause serious side effects.
Especially tell your healthcare provider if you take
other antidepressants, opioids, or Central Nervous System (CNS)
depressants (such as benzodiazepines).
Please see the patient Medication Guide, including
information about serious side effects, for ZULRESSO in the full
Prescribing Information.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210803005320/en/
Investor Contact Jeff Boyle 347-247-5089
jeff.boyle@sagerx.com
Media Contact Maureen L. Suda 617-949-4289
maureen.suda@sagerx.com
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