Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in
innovative pharmaceutically-produced transdermal cannabinoid
therapies for orphan neuropsychiatric disorders, today announced
positive top line results from the exploratory, open label Phase 2
INSPIRE (Assessing the
Impact of Zygel
[Tra
nsdermal CBD Gel] on
Pediatr
ic
Behavio
ral and
Emotional Symptoms
of 22q11.2 Deletion Syndrome) trial. Based on the positive Phase 2
data, the Company will request a meeting with the U.S. Food and
Drug Administration (FDA) to discuss the data and the regulatory
path forward.
The Phase 2 trial was designed for signal detection by assessing
the safety, tolerability and efficacy of Zygel (also known as
ZYN002) for the treatment of behavioral symptoms of chromosome
22q11.2 deletion syndrome (22q) in children and adolescents. Zygel
was administered to patients with 22q as add-on therapy to their
standard of care and utilized a variety of efficacy assessments.
Key findings from the trial disclosed today include:
- The total score and all five subscales
of the Anxiety, Depression and Mood Scale (ADAMS) showed
statistically significant improvements at 14 weeks of treatment
compared to baseline;
- All five subscales of the Aberrant
Behavior Checklist – Community (ABC-C) showed statistically
significant improvements at 14 weeks of treatment compared to
baseline;
- The Pediatric Anxiety Rating Scale
(PARS – R) showed statistically significant improvements at 14
weeks of treatment compared to baseline;
- The majority of
patients showed clinically meaningful improvements at week 14 as
demonstrated by the Clinical Global Impression – Improvement
(CGI-I). Seventy-five percent of patients were rated by the
clinicians as “improved”, “much improved” or “very much improved”
with nearly two-thirds (62.5%) of the patients being “much
improved” or “very much improved”;
- Zygel was shown to
be well tolerated, and the safety profile was consistent with
previously released data from other Zygel clinical trials.
“I am encouraged with the results from the INSPIRE trial,
particularly with the potential for real reductions in general
anxiety, social withdrawal, and social avoidance in children and
adolescents with chromosome 22q11.2 deletion syndrome,” said Tony
J. Simon, Ph.D. Professor Emeritus at the University of California,
Davis School of Medicine and the UC Davis MIND Institute. “I’m
especially encouraged that ZYN002 is a unique, cannabidiol gel free
of THC and manufactured to pharmaceutical specifications. Children
and adolescents with 22q should avoid THC which may increase the
likelihood of developing psychosis. I look forward to the further
development of ZYN002 for this underserved population.”
“We believe the data from this Phase 2 trial are very
encouraging and reinforce the potential of Zygel for the treatment
of behavioral symptoms in children and adolescents with 22q, and we
look forward to discussing the regulatory path forward with the FDA
with these data in hand,” said Armando Anido, Chairman and Chief
Executive Officer of Zynerba. “In the near term, we will focus our
resources on completing the RECONNECT trial for children and
adolescents with Fragile X syndrome and progressing 22q.”
INSPIRE Trial Design
The 14-week INSPIRE trial was an open-label, Phase 2 clinical
trial designed to evaluate the safety, tolerability and efficacy of
Zygel in children and adolescents (ages four through 15) with
genetically-confirmed 22q11.2 deletion syndrome. Enrolled patients
received weight-based doses of 250 mg or 500 mg daily of Zygel.
Patients were allowed to increase the daily dose after six weeks of
treatment to 500 mg and 750 mg if the investigator felt such
increase was appropriate. One patient’s dose was increased from 250
mg to 500 mg, and no patients increased to 750 mg in the treatment
period. At the completion of the trial, thirteen (13) patients
entered into an extension study for up to six months.
Patient Disposition and Baseline
Demographics
Twenty (20) patients were enrolled in the trial, which was
conducted at two clinical sites in Australia and one clinical site
in the U.S. All 20 patients are included in the safety analysis.
Seventeen (17) patients completed the 14-week trial and three
patients discontinued. One patient was lost to follow-up, one
patient withdrew due to adverse events not related to Zygel, and
one patient withdrew consent. Efficacy analyses included 16
patients as one patient did not have valid assessments at week
14.
The mean age of patients enrolled in the trial was 9.9 years,
and twelve (60%) of the patients were male. Patients weighed
between 13.7 and 79.8 kilograms (mean=37.4; median=33.5).
Top-line Efficacy Results
As a signal-seeking Phase 2 trial, multiple efficacy assessments
were administered, including the Anxiety, Depression and Mood Scale
(ADAMS), the Aberrant Behavior Checklist – Community (ABC-C), the
Pediatric Anxiety Ratings Scale (PARS – R) and Clinical Global
Impression – Severity and Improvement.
Results of the ADAMS:
|
|
|
|
|
|
Change from |
|
Mean % |
|
|
|
Median % |
Subscale |
|
Baseline |
|
Week 14 |
|
Baseline |
|
Improvement |
|
p Value |
|
Improvement |
|
|
|
|
|
|
|
|
|
|
|
|
|
Total Score |
|
36.1 |
|
17.7 |
|
-18.4 |
|
45.3% |
|
0.0005 |
|
43.0% |
General Anxiety |
|
10.4 |
|
5.1 |
|
-5.4 |
|
43.6% |
|
0.0005 |
|
48.8% |
Depressed Mood |
|
7.6 |
|
3.4 |
|
-4.3 |
|
50.3% |
|
0.0033 |
|
52.8% |
Social Avoidance |
|
8.7 |
|
4.3 |
|
-4.4 |
|
41.3% |
|
0.0084 |
|
50.0% |
Obsessive/Compulsive
Behavior |
|
3.0 |
|
1.1 |
|
-1.9 |
|
64.0% |
|
0.0037 |
|
66.7% |
Manic / Hyperactive
Behavior |
|
7.6 |
|
4.4 |
|
-3.1 |
|
38.2% |
|
0.0032 |
|
27.4% |
|
|
|
|
|
|
|
|
|
|
|
|
|
Results of the ABC-C:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Change from |
|
Mean % |
|
|
|
Median % |
Subscale |
|
Baseline |
|
Week 14 |
|
Baseline |
|
Improvement |
|
p Value |
|
Improvement |
|
|
|
|
|
|
|
|
|
|
|
|
|
Social Withdrawal |
|
14.4 |
|
7.9 |
|
-6.4 |
|
27.6% |
|
0.0110 |
|
46.4% |
Inappropriate Speech |
|
4.2 |
|
2.4 |
|
-1.8 |
|
18.3% |
|
0.0166 |
|
50.0% |
Stereotypic Behavior |
|
3.9 |
|
1.6 |
|
-2.3 |
|
52.1% |
|
0.0155 |
|
58.3% |
Irritability |
|
18.4 |
|
10.0 |
|
-8.4 |
|
36.3% |
|
0.0055 |
|
39.6% |
Hyperactivity |
|
18.1 |
|
10.4 |
|
-7.6 |
|
16.5% |
|
0.0091 |
|
38.1% |
|
|
|
|
|
|
|
|
|
|
|
|
|
Results of the PARS – R:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Change from |
|
Mean % |
|
|
|
Median % |
|
|
Baseline |
|
Week 14 |
|
Baseline |
|
Improvement |
|
p Value |
|
Improvement |
|
|
|
|
|
|
|
|
|
|
|
|
|
Total Score |
|
14.7 |
|
8.5 |
|
-6.2 |
|
40.6% |
|
0.0005 |
|
40.0% |
Results of the CGI-I:
The investigators rated 12 of 16 patients (75%) as improved,
“much improved” or “very much improved” at week 14, with 62.5%
being “much improved” or “very much improved”.
Safety Data
Zygel was shown to be well tolerated, and the safety profile was
consistent with previously released data from other Zygel clinical
trials. Three patients reported treatment related adverse events
which were all mild application site adverse events. One patient
discontinued treatment due to adverse events not related to
Zygel.
Prioritizing Orphan Development Programs; Cash Runway
Extended to Late 2023 / Early 2024
In the near term the Company has decided to prioritize its
resources on Fragile X syndrome (FXS) and 22q, both of which have
been granted orphan drug designation by the FDA and both of which
have no approved products. While the data from the Company’s autism
spectrum disorder (ASD) clinical development program to date are
compelling, given the difficult financing market, the Company will
defer the start of the Phase 3 development program in ASD
previously planned for the second half of 2022. As a result, the
Company now believes its $69.7 million of cash and cash equivalents
as of March 31, 2022 are sufficient to fund planned operations and
capital requirements through the end of 2023 or early 2024, after
the expected availability of top line results from its confirmatory
pivotal Phase 3 RECONNECT trial of Zygel in patients with FXS.
Conference call information
Zynerba management will host a live conference call and webcast
tomorrow, June 22, 2022, at 9:00 a.m. Eastern Time to discuss
results of the INSPIRE trial and updates to its clinical
development plans. The call can be accessed by dialing (866)
573-0180 (U.S. and Canada) or (430) 775-1345 (international) and
referencing conference ID 4453857. To access the live webcast or
the replay, visit the investor page of the Company’s website at
http://ir.zynerba.com/. The webcast will be recorded and available
on the Company’s website for 30 days.
About 22q11.2 Deletion Syndrome (22q)
As the second most common chromosomal disorder after Down
syndrome, 22q is caused by a small missing piece of the 22nd
chromosome. The deletion occurs near the middle of the chromosome
at a location designated q11.2. It is considered a mid-line
condition, with physical symptoms including characteristic palate
abnormalities, heart defects, immune dysfunction, and esophageal /
GI issues, as well as debilitating neuropsychiatric and behavioral
challenges. Anxiety is among the most common neuropsychiatric
symptoms of 22q and researchers have found that for children with
22q, anxiety is linked to poorer adaptive behaviors such as
self-care and communication skills that affect daily life. Children
with 22q also experience withdrawn behavior, ADHD, cognitive
impairment, and autism spectrum disorder that affect communication
and social interaction. Later in life, they are at an increased
risk of developing mental illnesses such as schizophrenia. It is
estimated that 22q occurs in between one in 3,000 and one in 6,000
live births, suggesting that there are approximately 83,000 people
living with 22q in the U.S.
About Zygel
Zygel is the first and only pharmaceutically-manufactured
cannabidiol formulated as a patent-protected permeation-enhanced
clear gel, designed to provide controlled drug delivery into the
bloodstream transdermally (i.e. through the skin). Recent studies
suggest that cannabidiol may modulate the endocannabinoid system
and improve certain behavioral symptoms associated with
neuropsychiatric conditions. Zygel is an investigational drug
product in development for the potential treatment of behavioral
symptoms associated with Fragile X syndrome (FXS), 22q11.2 deletion
syndrome (22q) and autism spectrum disorder (ASD). The Company has
received orphan drug designation for cannabidiol, the active
ingredient in Zygel, from the FDA and the European Commission for
the treatment of FXS and by the FDA for the treatment of 22q.
Additionally, Zygel has been designated a Fast Track development
program for treatment of behavioral symptoms of FXS.
About Fragile X Syndrome (FXS)
FXS is a rare genetic developmental disability that is the
leading known cause of both inherited intellectual disability and
autism spectrum disorder, affecting 1 in 3,600 to 4,000 males and 1
in 4,000 to 6,000 females. It is the most common inherited
intellectual disability in males and a significant cause of
intellectual disability in females, and the leading genetic cause
of autism spectrum disorder (ASD). The disorder negatively affects
synaptic function, plasticity and neuronal connections, and results
in a spectrum of intellectual disabilities and behavioral symptoms,
such as social avoidance and irritability. In the U.S., there are
approximately 78,000 people suffering with FXS, and approximately
121,000 in the EU and UK. We believe that approximately 60% of all
patients with FXS have complete methylation of their FMR1 gene.
About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative
pharmaceutically-produced transdermal cannabinoid therapies for
rare and near-rare neuropsychiatric disorders. We are committed to
improving the lives of patients and their families living with
severe, chronic health conditions including Fragile X syndrome,
22q11.2 deletion syndrome and autism spectrum disorder. Learn more
at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.
Cautionary Note on Forward-Looking
Statements
This press release contains forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. We may, in some cases, use terms such as “predicts,”
“believes,” “potential,” “proposed,” “continue,” “estimates,”
“anticipates,” “expects,” “plans,” “intends,” “may,” “could,”
“might,” “will,” “should” or other words that convey uncertainty of
future events or outcomes to identify these forward-looking
statements. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or
results to differ materially from the Company’s current
expectations. Management’s expectations and, therefore, any
forward-looking statements in this press release could also be
affected by risks and uncertainties relating to a number of other
factors, including the following: the Company’s cash and cash
equivalents may not be sufficient to support its operating plan for
as long as anticipated; the Company’s expectations, projections and
estimates regarding expenses, future revenue, capital requirements,
incentive and other tax credit eligibility, collectability and
timing, and availability of and the need for additional financing;
the Company’s ability to obtain additional funding to support its
clinical development programs; the results, cost and timing of the
Company’s clinical development programs, including any delays to
such clinical trials relating to enrollment or site initiation;
clinical results for the Company’s product candidates may not be
replicated or continue to occur in additional trials and may not
otherwise support further development in a specified indication or
at all; actions or advice of the U.S. Food and Drug Administration,
the European Medicines Agency and other foreign regulatory agencies
may affect the design, initiation, timing, continuation and/or
progress of clinical trials or result in the need for additional
clinical trials; the Company’s ability to obtain and maintain
regulatory approval for its product candidates, and the labeling
under any such approval; the Company’s reliance on third parties to
assist in conducting pre-clinical and clinical trials for its
product candidates; delays, interruptions or failures in the
manufacture and supply of the Company’s product candidates the
Company’s ability to commercialize its product candidates; the size
and growth potential of the markets for the Company’s product
candidates, and the Company’s ability to service those markets; the
Company’s ability to develop sales and marketing capabilities,
whether alone or with potential future collaborators; the rate and
degree of market acceptance of the Company’s product candidates;
the Company’s expectations regarding its ability to obtain and
adequately maintain sufficient intellectual property protection for
its product candidates; the extent to which health epidemics and
other outbreaks of communicable diseases, including COVID-19, could
disrupt our operations or adversely affect our business and
financial conditions; and the extent to which inflation or global
instability, including political instability, may disrupt our
business operations or our financial condition. This list is not
exhaustive and these and other risks are described in the Company’s
periodic reports, including the annual report on Form 10-K,
quarterly reports on Form 10-Q and current reports on Form 8-K,
filed with or furnished to the Securities and Exchange Commission
and available at www.sec.gov. Any forward-looking statements that
the Company makes in this press release speak only as of the date
of this press release. The Company assumes no obligation to update
forward-looking statements whether as a result of new information,
future events or otherwise, after the date of this press
release.
Zynerba Contacts
Peter VozzoICR WestwickeOffice: 443.213.0505Cell:
443.377.4767Peter.Vozzo@Westwicke.com
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