Pipeline progress continues with first patient
dosed and ongoing enrollment in multiple clinical trials across the
depression and neurology franchises
Durability of response was observed in patients
with MDD who responded to a 2-week treatment with zuranolone in
MOUNTAIN Study six-month follow-up period
Conference call today at 8:30 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,
2020.
During the quarter, Sage initiated enrollment and dosing in two
new trials with zuranolone 50 mg:
- Phase 3 SKYLARK Study (PPD-301) in postpartum depression
(PPD)
- Phase 3 WATERFALL Study (MDD-301B) in major depressive disorder
(MDD)
- Based on strong enrollment to date, topline data from this
study is now anticipated in first half of 2021
In addition, Sage initiated dosing in the 50 mg cohort of the
open-label Phase 3 SHORELINE Study and is on-track to initiate
dosing in 2H 2020 in the Phase 3 CORAL Study (MDD-305)
investigating zuranolone 50 mg as an acute rapid response therapy
(RRT) in patients with MDD when co-initiated with a newly
administered standard antidepressant therapy. The Company also
initiated dosing in the Phase 2 KINETIC Study evaluating SAGE-324
in patients with essential tremor and is on-track to initiate the
Phase 2 PARADIGM Study in the second half of 2020 evaluating
SAGE-718 in patients with Parkinson’s disease (PD) with impaired
cognitive function.
Sage also reported results from the 6-month follow-up cohort
with zuranolone 30 mg from the MOUNTAIN study. There were no
symptoms of withdrawal observed after discontinuation of zuranolone
(Day 14) and 74.5% of patients who responded to zuranolone
maintained their response at the last follow-up at Day 182.
Zuranolone was generally well-tolerated and showed a similar safety
profile as seen in earlier studies.
“We have created a novel drug company successfully able to
convert our chemical equity into a rich pipeline of clinical assets
that are new chemical entities, not repurposed molecules,” said
Jeff Jonas, M.D., chief executive officer at Sage Therapeutics.
“Even in the face of the difficulties currently challenging the
world, I’m pleased to report that the team at Sage is executing
across all three brain health franchises and we expect to report on
numerous catalysts in the next 18 months.”
Portfolio Updates Sage is
advancing a portfolio of novel, new chemical entities with the
potential to become differentiated products designed to improve
brain health by targeting the GABAA and NMDA receptor systems.
Dysfunction in these systems is thought to be at the core of
numerous neurological and neuropsychiatric disorders.
Depression 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 PPD. Zuranolone received
breakthrough therapy designation from the U.S. FDA for the
treatment of MDD.
- Zuranolone ongoing studies: Sage is evaluating the
potential of zuranolone as a rapid-acting, short-course treatment
for PPD and MDD. Sage recently initiated three new short-term
clinical studies in 2020, with the potential, if successful, for
three distinct indications: PPD, acute rapid response therapy (RRT)
in MDD when co-initiated with a new standard antidepressant, and
as-needed, or episodic, treatment of MDD. Enrollment and dosing are
now ongoing in two of these trials:
- SKYLARK (PPD-301) Study
investigating zuranolone as an oral therapy in women with PPD:
- Placebo-controlled trial evaluating a two-week course of
zuranolone 50 mg in women with PPD, with additional short-term
follow-up.
- Topline data from this study is anticipated in 2021.
- WATERFALL (MDD-301B) Study
investigating zuranolone for as-needed, or episodic, treatment in
MDD:
- Placebo-controlled trial evaluating a two-week course of
zuranolone 50 mg in patients with MDD, with additional short-term
follow-up.
- Based on strong enrollment to date, with more than 50%
enrolled, topline data from this study is now anticipated in the
first half of 2021.
Sage is on-track to commence dosing of the third new zuranolone
Phase 3 trial in 2020:
- CORAL (MDD-305) Study
investigating zuranolone for acute RRT in patients with MDD when
co-initiated with a newly administered standard antidepressant
therapy:
- Placebo-controlled trial evaluating a two-week course of
zuranolone 50 mg, when co-initiated with an open-label
antidepressant, in patients with MDD, with additional short-term
follow-up.
- Topline data from this study is anticipated in 2021.
Additional study updates:
- SHORELINE Study (MDD-303): The
Company is on track to report topline data in the second half of
2020 from patients with MDD who received zuranolone 30 mg in the
SHORELINE Study, designed to evaluate safety and tolerability of
as-needed repeat treatment over a 1-year period.
- Patient dosing has begun in a new 50 mg cohort of patients with
MDD; enrollment is ongoing.
- MOUNTAIN Study 6-month follow-up data: As part of the
MOUNTAIN Study, subjects were offered the opportunity to
participate in a 6-month, blinded follow-up to assess durability of
response. The study was not powered to detect statistical
significance beyond the Day 15 endpoint. More detailed data will be
prepared for presentation and publication.
- Of the subjects who were dosed in the MOUNTAIN Study,
approximately 50% agreed to join the 6-month follow-up period and
nearly 75% of patients who responded to zuranolone 30 mg at Day 15
maintained their response rate at the last follow-up on Day
182.
Safety:
- No drug-related adverse events, changes in laboratories, ECG
measures, vital signs, or suicidality ratings were present over the
long-term following exposure to zuranolone. Zuranolone was
generally well-tolerated and showed a similar safety profile as
seen in earlier studies.
- There were no signals of withdrawal or rebound after treatment
with zuranolone was completed.
Durability of treatment:
- In subjects with response after the 14-day treatment period
(Day 15), a large majority maintained this response throughout the
6-month follow-up regardless of arm.
- Out of responders to zuranolone 30 mg at Day 15 (N=77), a large
majority (74.5%) maintained their response rate at the last follow
up at Day 182.
- This continued benefit was seen with all efficacy measures over
the 6-month follow-up period: (17-item Hamilton Rating Scale for
Depression (HAM-D), Clinician Global Impression – Improvement
(CGI-I), Clinician Global Impression – Severity (CGI-S).
- Sage’s collaboration with Shionogi & Co., Ltd. is
progressing, with Shionogi initiating a Phase 2 trial with
zuranolone in Japan for the treatment of MDD. Under terms of
collaboration, Shionogi is responsible for all clinical
development, regulatory filings and commercialization of zuranolone
for MDD, and potentially other indications, in Japan, Taiwan and
South Korea.
- Sage is also currently evaluating the ongoing zuranolone
clinical pharmacology and safety program and plans to finalize
requirements to support a potential future NDA with the FDA.
- ZULRESSO™ (brexanolone) CIV injection:
- Revenue in the second quarter of 2020 from sales of ZULRESSO
was $1.1 million, compared to $2.3 million in the first quarter of
2020. In April 2020, as a part of the Company’s restructuring, Sage
downsized commercial efforts, including elimination of its entire
salesforce. The Company now has a small commercial team with a
primary focus on working with healthcare providers and supporting
women with PPD in geographies with active, ZULRESSO treating
sites.
- The rapid spread of COVID-19 in the U.S. resulted in multiple
sites of care pausing treatment of new patients with ZULRESSO
during the quarter. Concerns about exposure to the virus have also
caused a significant reduction in the number of women with PPD
seeking treatment with ZULRESSO and in physicians willing to
prescribe it. Given the ongoing surge in the number of cases of
COVID-19 in the U.S. and continuing concerns about the pandemic
across the country, the Company expects the significant adverse
impact of the pandemic on ZULRESSO revenues to continue. The
Company does not plan to provide revenue guidance for the balance
of 2020.
- The Company has received clearance from the U.S. FDA, under the
Coronavirus Treatment Acceleration Program (CTAP), to initiate a
Phase 3 study with brexanolone in patients with advanced COVID-19
related acute respiratory distress syndrome (ARDS).
- Additional information about this program will be provided
during Sage’s upcoming FutureCast investor day planned for
September.
Neurology Franchise
SAGE-324, a next-generation PAM of GABAA receptors and Sage’s lead
neurology asset, is in development as a potential oral therapy for
neurological conditions, such as essential tremor (ET), epilepsy
and Parkinson’s disease.
- SAGE-324: Sage initiated enrollment and dosing in the
KINETIC Study (324-ETD-201), a placebo-controlled Phase 2 study
evaluating the safety and efficacy of SAGE-324 in patients with ET.
Patients will receive a once-daily, four-week course of SAGE-324 60
mg or placebo.
- Topline data from this study is anticipated in 4Q 2020/1Q
2021.
Neuropsychiatry 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),
Parkinson’s disease (PD) and Alzheimer’s disease (AD).
- SAGE-718: The Company is on-track to initiate the
PARADIGM Study (718-CNP-201), a Phase 2a open-label study in 2020
evaluating SAGE-718 in patients with PD cognitive dysfunction.
- Results from this study will inform potential advancement of
SAGE-718 into further development.
- Topline data from this study is anticipated in 2H 2020.
Anticipated Upcoming
Milestones
2H 2020
- Zuranolone:
- Initiate dosing in Phase 3 CORAL (MDD-305) Study evaluating a
two-week course of zuranolone 50 mg, when co-initiated with an
open-label anti-depressant, as an acute rapid response therapy in
patients with MDD.
- Report topline data from Phase 3 SHORELINE (MDD-303 – 30 mg)
Study.
- Brexanolone:
- Initiate Phase 3 study in patients with advanced COVID-19
related acute respiratory distress syndrome (ARDS).
- SAGE-718:
- Report topline data from Phase 2a study in patients with
Parkinson’s disease cognitive dysfunction.
- SAGE-324:
- Report topline data from Phase 2 placebo-controlled study in ET
(4Q 2020/1Q 2021).
2021
- Zuranolone:
- Report topline data from Phase 3 WATERFALL Study (1H 21).
- Report topline data from Phase 3 SKYLARK Study.
- Report topline data from Phase 3 CORAL Study.
- Report topline data from Phase 3 SHORELINE Study (50 mg).
Financial Results for the Second
Quarter 2020
- Revenue: Sage recorded $1.1 million in net revenue in
the second quarter of 2020 from sales of ZULRESSO, compared to $0.5
million for the same period in 2019. Sage recorded no collaboration
revenue in the second quarter of 2020 compared to $0.4 million in
collaboration revenue from Shionogi & Co., Ltd. related to
reimbursement of product expense for the same period in 2019.
- Cash Position: Cash, cash equivalents, restricted cash,
and marketable securities as of June 30, 2020 were $759 million
compared to $875 million at March 31, 2020.
- R&D Expenses: Research and development expenses were
$73.3 million, including $10.1 million of non-cash stock-based
compensation expense, in the second quarter of 2020 compared to
$89.1 million, including $13.7 million of non-cash stock-based
compensation expense, for the same period in 2019. The decrease in
R&D expenses was primarily related to the completion of the
MOUNTAIN Study, a Phase 3 clinical trial of zuranolone in MDD and
the decrease in non-cash stock-based compensation expense.
- SG&A Expenses: Selling, general and administrative
expenses were $38.2 million, including $12.1 million of non-cash
stock-based compensation expense, in the second quarter of 2020
compared to $88.2 million, including $21.1 million of non-cash
stock-based compensation expense, for the same period in 2019. The
decrease in SG&A expenses was primarily due to the
restructuring that the Company announced during the second quarter
of 2020.
- Restructuring Expenses: Restructuring expenses were
$28.4 million in the second quarter of 2020 compared to none for
the same period in 2019.
- Net Loss: Net loss was $136.3 million for the second
quarter of 2020, compared to $168.2 million for the same period in
2019.
Financial Guidance
- Sage anticipates a cash balance of at least $550 million at end
of 2020, which the Company anticipates will support operations into
2022 based on current operating plans.
Conference Call Information Sage will host a conference
call and webcast today, Monday, August 10, 2020, at 8:30 a.m. ET to
discuss its second quarter 2020 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 revenues from sales of
ZULRESSO and the expected continuing impact of the COVID-19
pandemic on ZULRESSO revenues; our clinical development plans and
expected timelines; our expectations with respect to 2020 operating
expenses and year-end cash; our belief that existing cash will
support operations into 2022; our belief in the potential of our
product candidates in various indications; the potential profile
and benefit of our product candidates; and the goals, opportunity
and potential for our business. 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 never be able to generate meaningful revenues from sales of
ZULRESSO or to generate revenues at levels necessary to justify our
investment; the impact of the COVID-19 pandemic on sales of
ZULRESSO may last longer than we expect or may reoccur in waves;
our post-restructuring focus on geographies where there are
existing, active ZULRESSO treating sites may not be sufficient for
us to achieve success from the sale of ZULRESSO or to generate
revenues at meaningful levels or at levels necessary to justify our
investment even after the impact of the COVID-19 pandemic lessens;
we may not be able to overcome the barriers to treatment with
ZULRESSO or we may continue to encounter other issues or challenges
in commercializing ZULRESSO which could further limit the potential
of ZULRESSO and the timing and amount of future revenues; results
achieved with use of ZULRESSO in the treatment of PPD in commercial
use may be different than observed in clinical trials, and may vary
among patients; the number of women with PPD or the unmet need for
additional treatment options may be significantly smaller than we
expect; we may encounter delays in initiation or conduct of our
ongoing and planned clinical trials, including slower than expected
site initiation or enrollment, that may impact our ability to meet
our expected time-lines and increase our costs; we may not be able
to mitigate the impact of COVID-19 on our clinical development
timelines and the impact may be more significant than we expect and
may negatively impact expected site initiation, enrollment or
conduct in our clinical trials, or cause us to pause trials or not
be able to use data, in each case which may significantly impact
our ability to meet our expected time-lines or may significantly
impact the integrity or sufficiency of the data from our trials or
increase our costs or cause us to have to change our plans; 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; our expectations as to expenses, year-end cash and cash needs
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; 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; success in our non-clinical
studies or in earlier clinical trials 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; 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 different or more severe adverse events at the higher
doses we are planning to study in new trials; we may encounter
issues with the efficacy or durability of short-term treatment, or
co-initiated treatment with zuranolone or safety and efficacy
concerns with respect to retreatment that require additional
studies be conducted; the FDA may ultimately decide that the design
or results of our completed and planned clinical trials for any of
our product candidates, even if positive, are not sufficient for
regulatory approval in the indications that are the focus of our
development plan; 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; we may encounter technical and
other unexpected hurdles in the development and manufacture of our
product candidates which may delay our timing or change our plans
or increase our costs; 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 March
31, Six Months Ended June 30,
2020
2019
2020
2019
Product revenue, net
$
1,089
$
519
$
3,375
$
519
Collaboration revenue
-
354
-
819
Total revenue
1,089
873
3,375
1,338
Operating
costs and expenses:
Cost of goods sold
110
44
280
44
Research and development
73,320
89,059
136,930
175,457
Selling, general and administrative
38,224
88,227
108,355
172,146
Restructuring
28,402
-
28,402
-
Total operating costs and expenses
140,056
177,330
273,967
347,647
Loss from operations
(138,967
)
(176,457
)
(270,592
)
(346,309
)
Interest
income, net
2,686
8,220
7,416
14,662
Other income (expense), net
(66
)
16
89
20
Net loss
$
(136,347
)
$
(168,221
)
$
(263,087
)
$
(331,627
)
Net loss per share - basic and diluted
$
(2.63
)
$
(3.28
)
$
(5.07
)
$
(6.65
)
Weighted average shares outstanding - basic and diluted
51,926,074
51,257,640
51,917,417
49,882,377
Sage Therapeutics, Inc. and Subsidiaries Condensed
Consolidated Balance Sheets (in thousands) (unaudited)
June
30,2020 December 31,2019 Cash, cash
equivalents, restricted cash and investments
$
758,889
$
1,010,760
Total assets
$
827,242
$
1,084,150
Total liabilities
$
87,327
$
139,495
Total stockholders' equity
$
739,915
$
944,655
About ZULRESSO™ (brexanolone) CIV injection ZULRESSO, the
first medicine specifically approved by the U.S. Food and Drug
Administration (FDA) for the treatment of postpartum depression
(PPD) in adults, is a positive allosteric modulator of both
synaptic and extrasynaptic GABAA receptors. Allosteric modulation
of neurotransmitter receptor activity results in varying degrees of
desired activity rather than complete activation or inhibition of
the receptor.
SELECT IMPORTANT SAFETY INFORMATION These are not all the
side effects of ZULRESSO.
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 untilyour 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/20200810005142/en/
Investors Jeff Boyle 617-949-4256
Jeff.Boyle@sagerx.com
Media Maureen L. Suda 617-949-4289
maureen.suda@sagerx.com
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