Author: Jennifer Guinan

– RECONNECT, a confirmatory pivotal trial of Zygel™ in patients with FXS, expected to be initiated in the third quarter of 2021 –

– Cash runway well into first half 2024; $93.1 million at March 31, 2021 –

Devon, PA, May 12, 2021 – Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today reported financial results for the first quarter ended March 31, 2021, and provided an overview of recent operational highlights and a pipeline update.

“We are committed to delivering on our important milestones in 2021 as we develop Zygel in multiple neuropsychiatric indications, including initiating a confirmatory pivotal Phase 3 trial, RECONNECT, in the third quarter of 2021, after productive dialogue and alignment with the FDA,”said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “With a cash runway that takes us well into the first half of 2024, we believe that we are ideally positioned to continue our efforts to develop the first FDA approved treatment for patients with Fragile X syndrome.”

First Quarter 2021 and Recent Highlights and Zygel Pipeline Update

Zygel in Fragile X Syndrome (FXS)

• Zynerba expects to initiate RECONNECT (A Randomized, Double-Blind, Placebo-Controlled, Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome), a pivotal, multi-national confirmatory Phase 3 trial of Zygel in children and adolescents with FXS, in the third quarter of 2021. The trial is designed to confirm the positive results observed in a population of responders in the Company’s previously conducted CONNECT-FX trial.  (Press release)
• The RECONNECT trial will be an 18-week trial which will enroll approximately 200 children and adolescents of which approximately 160 patients will have complete (100%) methylation of their FMR1 gene and approximately 40 patients will have partial methylation of their FMR1 gene. The primary endpoint for the trial will be the change in the Aberrant Behavior Checklist-Community FXS Specific (ABC-C_FXS) Social Avoidance subscale in patients who have complete methylation of their FMR1 gene. All patients, including the cohort of partially methylated patients, will be included in a key secondary endpoint analysis. The Company believes that the results, if positive, from RECONNECT will be sufficient to support the submission of a New Drug Application for Zygel in patients with FXS.
• Presented data at the Society of Biological Psychiatry (SOBP) 2021 Virtual Meeting demonstrating that the ABC-C_FXS subscales capture behaviors that are impactful and meaningful in clinical trials of children with FXS. Furthermore, the data showed that Zygel provided meaningful improvements in behavioral symptoms of FXS in patients with ≥90% methylation of the FMR1 gene. (Press release)
• Presented data at the SOBP 2021 Virtual Meeting suggesting that effective silencing of the FMR1 gene may have led to differences in treatment response in patients with ≥90% methylation of the FMR1 gene in the CONNECT-FX trial. In the ≥90% methylation group of CONNECT-FX, Zygel was superior to placebo in multiple analyses, including reaching statistical significance on the primary endpoint in a pre-planned ad hoc analysis. (Press release)

Zygel in 22q11.2 Deletion Syndrome (22q)

• As the COVID-19-related restrictions in Australia are easing, the Company has resumed screening of patients for the 14-week open label Phase 2 INSPIRE trial in children and adolescents with genetically confirmed 22q.  Once enrollment is complete, a timeframe for disclosing topline results of the trial will be provided.

Zygel in Autism Spectrum Disorder (ASD)

• In the first half of 2021, Zynerba intends to discuss with the FDA data supporting the potential efficacy of Zygel in ASD, including the results of the Phase 2 BRIGHT trial in children and adolescents with moderate to severe ASD, to determine the regulatory path forward.

Zygel in Developmental and Epileptic Encephalopathies (DEE)

• Zynerba is conducting an observational trial that will help finalize target syndrome selection in one or more DEE syndromes in 2021. Due to the heterogeneity of patients who fall under the DEE umbrella, Zynerba will pursue individual syndromes rather than considering DEE as a single disorder or condition (Press release).  

First Quarter 2021 Financial Results
Research and development expenses were $4.6 million for the first quarter of 2021, including stock-based compensation of $0.6 million. General and administrative expenses were $3.3 million in the first quarter of 2021, including stock-based compensation expense of $0.6 million. The net loss for the first quarter of 2021 was $8.0 million with basic and diluted loss per share of $(0.20). 

Financial Outlook
In August 2019, the Company entered into a Controlled Equity Offering^SM Sales Agreement (the “2019 Sales Agreement”) with Cantor Fitzgerald & Co., Canaccord Genuity, LLC, H.C. Wainwright & Co. LLC and Ladenburg Thalmann & Co. Inc., as sales agents. In the first quarter of 2021, the Company sold and issued 10,244,326 shares of common stock under the 2019 Sales Agreement in the open market at a weighted average selling price of $4.22 per share, resulting in gross proceeds of $43.2 million. Net proceeds after deducting commissions and offering expenses were $42.2 million.

As of March 31, 2021, cash and cash equivalents were $93.1 million, compared to $59.2 million as of December 31, 2020. Management believes that the Company’s cash and cash equivalents as of March 31, 2021 are sufficient to fund operations and capital requirements well into the first half of 2024.

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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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 and 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 timing and outcome of current and future legal proceedings; and 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. 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 PHARMACEUTICALS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED BALANCE SHEETS

Zynerba Contacts
Jim Fickenscher, CFO and VP Corporate Development
Zynerba Pharmaceuticals
484.581.7483
fickenscherj@zynerba.com

Peter Vozzo
Westwicke/ICR
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

 – Confirmatory pivotal trial expected to be initiated in the third quarter of 2021 –

– Zynerba to hold conference call today, May 5, 2021 at 5:30 pm ET –

Devon, PA, May 5, 2021 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced the Company has received guidance from the U.S. Food and Drug Administration (FDA) on a confirmatory Phase 3 trial of Zygel in patients with Fragile X syndrome (FXS). The trial, which will be called RECONNECT (A Randomized, Double-Blind, Placebo-Controlled, Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome), is designed to evaluate the efficacy and safety of Zygel in children and adolescents with FXS. The study is planned to confirm the positive results observed in a population of responders in the Company’s CONNECT-FX trial, a randomized, double-blind, placebo-controlled trial that assessed the efficacy and safety of Zygel as a treatment for the behavioral symptoms of FXS previously conducted by the Company. The Company believes that the results, if positive, from RECONNECT will be sufficient to support the submission of a New Drug Application for Zygel in patients with FXS.

“Following productive discussions and alignment with the FDA, we believe we have a clear path forward for Zygel in Fragile X syndrome. We are excited to advance Zygel into the RECONNECT trial, a pivotal, multi-national, confirmatory Phase 3 trial in patients with FXS in the third quarter of 2021,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “If the results are positive, Zygel could become the first FDA approved treatment option for the significant unmet medical need that affects patients with FXS and their families.”

The RECONNECT trial will be an 18-week trial which will enroll approximately 200 children and adolescents of which approximately 160 patients will have complete (100%) methylation of their FMR1 gene and approximately 40 patients will have partial methylation of their FMR1 gene. The primary endpoint for the trial will be the change in the Aberrant Behavior Checklist-Community FXS Specific (ABC-C_FXS) Social Avoidance subscale in patients who have complete methylation of their FMR1 gene. All patients, including the cohort of partially methylated patients, will be included in a key secondary endpoint analysis.

Complete Methylation Results from CONNECT-FX
The Company performed an analysis of the CONNECT-FX population within those patients having complete methylation of their FMR1 gene (n = 137 of 212 in the intent to treat population) to evaluate the effect of Zygel versus placebo. One patient did not have a post-baseline efficacy measure and was therefore not included in the efficacy analysis.

Baseline demographics for patients with complete methylation of the FMR1 gene are shown below. The group is similar to the previously reported full data set of patients and the cohort of patients with ≥90% methylation. The majority of patients were male and the children had a mean age of 9 to 10 years old.

	Placebo	Zygel	Total
n	65	72	137
Age (years)	9.7	9.5	9.6
Sex – Males
n	43	47	90
%	66%	65%	66%
Weight – kg:
Median	34.5	35.7	35.2
Range – Min, Max	16.8, 104.7	18.6, 87.0	16.8, 104.7
Baseline psychoactive medications, %	69%	56%	62%

The results in the cohort of patients with complete methylation of the FMR1 gene across the primary and key secondary endpoints that will be used in the RECONNECT trial are summarized below.

	Placebo N=64		Zygel N=72
	Baseline Mean	Week 12 Mean Change	Baseline Mean	Week 12 Mean Change	Treatment Difference**	Odds Ratio	Treatment P-Value
Primary Endpoint:
ABC-CFXS Social Avoidance Subscale	7.25	-1.84	6.88	-2.92	-1.08		0.027*
Secondary Endpoints:
ABC-CFXS Irritability Subscale	27.84	-3.98	28.89	-5.83	-1.85		0.220
CGI-I at Week 12 (Any Improvement)	–	36%	–	50%		1.75	0.128

^{*Statistically significant vs. placebo
**A negative treatment difference demonstrates that Zygel patients improved versus placebo}

“The treatment difference versus placebo and p value on the primary endpoint of improvement in the ABC-C_FXS Social Avoidance subscale in patients with complete methylation are consistent with the previously reported findings in patients with at least 90% methylation, despite the fact that the study was not powered to evaluate either of these patient populations.” said Dr. Joseph Palumbo, Chief Medical Officer of Zynerba Pharmaceuticals, Inc. “We believe the CONNECT-FX trial was instrumental in advancing our understanding of the science of Fragile X Syndrome. We look forward to leveraging what we learned as we seek to confirm our findings in the RECONNECT trial.”

Conference Call Information
Zynerba management will host a live conference call and webcast today at 5:30 pm Eastern Time to discuss the design of the RECONNECT Trial. The call can be accessed by dialing (800) 708-4540 (U.S. and Canada) or (847) 619-6397 (international) and referencing conference ID 50161974. 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 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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.  

About Fragile X Syndrome (FXS)
Fragile X syndrome 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 US, there are about 71,000 people suffering with FXS, approximately 60% of whom have complete methylation of the FMR1 gene.

FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including important effects on the endocannabinoid system, and most critically, codes for a protein called FMRP. This protein helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat. In most neurotypical people, the FMR1 gene correctly codes for the FMRP protein. In neurotypical individuals, there are CGG repeats, but these repeats only occur between 5 and 40 times. As a result, FMRP is manufactured at levels that enable control over behaviors like social avoidance and anxiety. In people with full mutation of the Fragile X gene, the CGG segment is repeated more than 200 times and in most cases causes the FMR1 gene to not function. However, the methylation of the FMR1 gene also plays a role in determining functionality of the gene. For patients with complete (100%) methylation, the FMR1 gene is silenced, therefore, no FMRP is produced, and the systems and processes that are expected to be affected by FMRP become dysregulated.

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, including the RECONNECT trial, 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; the Company’s planned RECONNECT trial may not be determined to be sufficient to support an NDA submission; actions or advice of the U.S. Food and Drug Administration and 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 timing and outcome of current and future legal proceedings; and 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. 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 Vozzo
Westwicke/ICR
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

DEVON, PA, April 29, 2021 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, is presenting two posters at the Society of Biological Psychiatry (SOBP) 2021 Virtual Meeting. Both posters will be made available on the Zynerba corporate website at the time of their presentations at http://zynerba.com/publications/.

The first poster titled, “Cannabidiol in Fragile X Syndrome (FXS): Proposed Mechanism of Action (MOA) Translates Into Meaningful Clinical Benefits [CONNECT-FX (ZYN2-CL-016)]” describes responder thresholds representing individual patient-level changes that the company believes are indicative of meaningful treatment benefit for the ABC-C_FXS social avoidance, irritability, and socially unresponsive/lethargic subscales. The authors concluded:

• Responder thresholds for meaningful within-patient behavioral change on key domains of the ABC-C_FXS were determined using anchor-based methods based upon FDA guidance for caregiver-reported outcomes
• The responder thresholds for meaningful within-patient behavioral change in CONNECT-FX corresponded to the following reductions
  • 3 or more points on the ABC-C_FXS Social Avoidance subscale
  • 9 or more points on the ABC-C_FXS Irritability subscale
  • 5 or more points on the ABC-C_FXS Socially Unresponsive/Lethargic subscale
• These thresholds serve as a basis for evaluating clinically meaningful treatment effects at the individual patient level in clinical trials of children and adolescents with FXS as demonstrated for Zygel (ZYN2) in CONNECT-FX
• Zygel provided meaningful improvements in behavioral symptoms of FXS in patients with ≥90% methylation of the FMR1 gene.

The poster, with submission ID #3010113, will be presented today in Poster Session I beginning at 12:15 p.m. CT (1:15 p.m. ET).

“We believe these data demonstrate the ABC-C_FXS subscales capture behaviors that are impactful and meaningful in clinical trials of children with FXS,” said Joseph M. Palumbo, M.D., LFAPA, MACPsych, Chief Medical Officer of Zynerba. “Therefore, we remain confident that these subscales are fit for purpose for measuring clinical trial endpoints in FXS.”

The second poster titled, “A Pivotal Study of ZYN002 Cannabidiol (CBD) Transdermal Gel in Children and Adolescents With Fragile X Syndrome [CONNECT-FX (ZYN2-CL-016)]” will be presented on April 30, 2021 and focuses on the findings in the CONNECT-FX study for the 80% of randomized patients whose FMR1 genes were highly methylated. This poster, with submission ID #3010130 will be presented tomorrow in Poster Session II beginning at 12:00 p.m. CT (1:00 p.m. ET).

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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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 and 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 timing and outcome of current and future legal proceedings; and 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. 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.

Investor Contact
Peter Vozzo
Westwicke/ ICR
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

Devon, PA, April 15, 2021 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced the acceptance and presentation details of two posters at the Society of Biological Psychiatry (SOBP) 2021 Virtual Meeting. The SOBP annual meeting is being held virtually from April 29 through May 1, 2021. A copy of the posters will be made available on the Zynerba corporate website at the time of presentations at http://zynerba.com/publications/.   

Title:  “Cannabidiol in Fragile X Syndrome (FXS): Proposed Mechanism of Action (MOA) Translates Into Meaningful Clinical Benefits [CONNECT-FX (ZYN2-CL-016)]”

Submission ID:  3010113
Session:  Poster Session I
Presentation Date:  April 29, 2021

Title:  “A Pivotal Study of ZYN002 Cannabidiol (CBD) Transdermal Gel in Children and Adolescents With Fragile X Syndrome [CONNECT-FX (ZYN2-CL-016)]”

Submission ID:  3010130
Session:  Poster Session II
Presentation Date:  April 30, 2021

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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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 and 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 timing and outcome of current and future legal proceedings; and 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. 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.

Investor Contact
Peter Vozzo
Westwicke/ ICR
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

Devon, PA, April 6, 2021 – Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that Armando Anido, Chief Executive Officer of Zynerba, will present a company overview during the 20^th Annual Needham Virtual Healthcare Conference on Monday, April 12, 2021 at 1:30 p.m. ET.  

Investors interested in arranging a virtual meeting with the Company’s management during the conference should contact the Needham conference coordinator. A webcast of the presentation will be available under the Events & Webcasts tab of the Investors section of the Zynerba website at www.zynerba.com. An archived replay will be available on the Company’s website following the event for 60 days.

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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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.  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.

Investor Contact
Peter Vozzo
Westwicke/ICR
Office: 443-213-0505
Cell: 443-377-4767
peter.vozzo@westwicke.com

 

Devon, PA, March 10, 2021 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today reported financial results for the fourth quarter and full year ended December 31, 2020, and provided an overview of recent operational highlights and a pipeline update.

“We expect to make significant progress in 2021 on all four indications for which we are developing Zygel, including initiating a pivotal trial in patients with Fragile X syndrome who have a highly methylated FMR1 gene to confirm the positive results in this population of responders in the CONNECT-FX trial,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “Screening in the INSPIRE trial of patients with 22q11.2 deletion syndrome has resumed now that COVID-19 restrictions in Australia have begun to ease. Once enrollment is complete we will update our expectation on when we will see topline results for this trial.”

Operational Highlights and Pipeline Update

Zygel™ in Fragile X Syndrome (FXS)

• Zynerba expects to initiate a single double-blind, placebo-controlled pivotal trial before the end of 2021 in patients with FXS who have a highly methylated FMR1 gene to confirm the positive results observed in this population of responders in the CONNECT-FX trial. The Company believes that positive results from this confirmatory pivotal trial will be sufficient to support the submission of a New Drug Application for Zygel in FXS. (Press release)
• Zynerba will review the trial design and protocol for the new confirmatory pivotal trial through a Type C meeting with the U.S. Food and Drug Administration (FDA) in the first half of 2021.

Zygel in 22q11.2 Deletion Syndrome (22q)

• The Company has initiated a second clinical site in Australia for the 14-week open label Phase 2 INSPIRE trial in children and adolescents with genetically confirmed 22q.
• As the COVID-19-related restrictions in Australia are easing, the Company has resumed screening of patients for this trial. Once enrollment is complete, a timeframe for disclosing topline results of the trial will be provided. In September 2020, the Company was granted orphan drug designation from the FDA for the use of cannabidiol for the treatment of 22q.

Zygel in Autism Spectrum Disorder (ASD)

• In the first half of 2021, Zynerba intends to discuss with the FDA data supporting the potential efficacy of Zygel in ASD, including the results of the Phase 2 BRIGHT trial in children and adolescents with moderate to severe ASD, to determine the regulatory path forward.

Zygel in Developmental and Epileptic Encephalopathies (DEE)

• Zynerba expects to conduct an observational trial that will help finalize target syndrome selection in one or more DEE syndromes in 2021.
  
  Zynerba concluded its iterative discussions with the FDA utilizing their ‘Written Response Only’ (WRO) meeting format regarding the clinical pathway for Zygel in DEE during which the FDA expressed support for a development program which would evaluate the treatment of focal-impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS). Due to the heterogeneity of patients who fall under the DEE umbrella, Zynerba will pursue individual syndromes rather than considering DEE as a single disorder or condition (Press release). The Company expects to conduct an observational trial that will help finalize target syndrome selection in one or more DEE syndromes by the end of 2021.
  
• New efficacy data presented at the 2020 annual meeting of the American Epilepsy Society show strong evidence of seizure reduction.
  
  The new efficacy data from the Phase 2 BELIEVE trial (Open Label Study to Assess the Safety and Efficacy of Zygel Administered as a Transdermal Gel to Children and Adolescents with DEE) describe strong evidence of seizure reduction over 12 months of treatment, including a 73% median reduction from baseline in FIAS and TCS seizure frequency at month 12. Furthermore, in the subgroup of patients with ASD, Zygel demonstrated meaningful reductions in FIAS and TCS seizures, with most children reaching either the 35% or 50% responder threshold by month three and month six, respectively.
  
  The data also show that Zygel improved the profound sleep disturbance experienced by patients with DEE who were enrolled in the trial (Press release).

Fourth Quarter and Full Year 2020 Financial Results

Research and development expenses were $5.6 million for the fourth quarter of 2020, including stock-based compensation of $0.6 million. General and administrative expenses were $4.6 million in the fourth quarter of 2020, including stock-based compensation expense of $0.6 million. The net loss for the fourth quarter of 2020 was $9.6 million with basic and diluted loss per share of $(0.33).

Research and development expenses were $35.7 million for full year 2020, including stock-based compensation of $2.2 million. General and administrative expenses were $16.4 million for full year 2020, including stock-based compensation expense of $3.0 million. The net loss for the full year 2020 was $51.3 million with basic and diluted net loss per share of $(1.90).

Financial Outlook

As of December 31, 2020, cash and cash equivalents were $59.2 million, compared to $70.1 million as of December 31, 2019. In August 2019, we entered into a Controlled Equity Offering Sales Agreement^SM, or the 2019 Sales Agreement, with Cantor Fitzgerald & Co., Canaccord Genuity, LLC, H.C. Wainwright & Co. LLC and Ladenburg Thalmann & Co. Inc., as sales agents pursuant to which we may sell, from time to time, up to $75.0 million of our common stock. In the fourth quarter of 2020, we sold and issued 558,089 shares of our common stock under the 2019 Sales Agreement in the open market resulting in gross proceeds of $1.9 million and net proceeds of $1.9 million, after deducting commissions and offering expenses. From January 1, 2021 through February 9, 2021, we have sold and issued 10,244,326 shares of our common stock under the 2019 Sales Agreement in the open market resulting in gross proceeds of $43.2 million and net proceeds of $42.2 million, after deducting commissions and offering expenses. As of February 9, 2021, we have utilized the entire $75 million authorized under the 2019 Sales Agreement, which was terminated pursuant to its terms.

Management believes that cash and cash equivalents, including the $42.2 million in net proceeds from issuances between January 1 and February 9, 2021 under the 2019 Sales Agreement, are sufficient to fund operations and capital requirements well into the first half of 2024.

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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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 and 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 timing and outcome of current and future legal proceedings; and 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. 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 PHARMACEUTICALS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS

 

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED BALANCE SHEETS

Zynerba Contacts
Jim Fickenscher, CFO and VP Corporate Development
Zynerba Pharmaceuticals
484.581.7483
fickenscherj@zynerba.com

Peter Vozzo
Westwicke/ICR
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

Devon, PA, March 4, 2021 – Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that Company management will participate in the 33^rd Annual ROTH Conference, which will be held virtually on March 15-17, 2021.

Investors interested in arranging a virtual meeting with the Company’s management on Wednesday, March 17, should contact the ROTH conference coordinator or brandon.weiner@westwicke.com.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in 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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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.  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.

Investor Contact
Peter Vozzo
Westwicke, an ICR Company
Office: 443-213-0505
Cell: 443-377-4767
peter.vozzo@westwicke.com

 

Devon, PA, January 4, 2021 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that Armando Anido, Chief Executive Officer of Zynerba, will participate in two upcoming virtual investor conferences. Mr. Anido will participate in a fireside chat during the H.C. Wainwright BioConnect Conference which will be available on demand January 11-14, 2021. He will also present a company overview during the ICR Conference 2021 on Thursday, January 14, 2021 at 10:00 a.m. ET.

Investors interested in arranging a virtual meeting with the Company’s management during the ICR Conference 2021 should contact the conference coordinator or brandon.weiner@westwicke.com. Webcasts of both conferences will be accessible under the Events & Webcasts tab of the Investor section of Zynerba’s website at www.zynerba.com.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in 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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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. 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.

Investor Contact
Peter Vozzo
Westwicke, an ICR Company
Office: 443-213-0505
Cell: 443-377-4767
peter.vozzo@westwicke.com

– Single Trial to be Conducted in Patients with Fragile X Syndrome to Confirm Positive Results Seen in the Population of Responders in the CONNECT-FX Trial –

– Conference Call and Webcast Today, December 17, 2020 at 8:30 am ET –

DEVON, Pa., December 17, 2020 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today provided an update on its meeting with the U.S. Food and Drug Administration (FDA) regarding its Fragile X syndrome (FXS) program. The Company plans to conduct a double-blind, placebo-controlled pivotal trial in patients with FXS who have a highly methylated FMR1 gene to confirm the positive results observed in this population of responders in the CONNECT-FX trial. In the first half of 2021, Zynerba will review the trial design and protocol for the new trial through a Type C meeting with the FDA and expects to initiate the pivotal trial before the end of 2021. Zynerba believes that positive results from this confirmatory trial would be sufficient to support the submission of a New Drug Application (NDA) for Zygel™ in FXS.

“We believe that Zygel has the potential to meaningfully relieve the behavioral symptoms of the most impacted individuals with Fragile X syndrome. We are committed to bringing this important therapy to patients and their families within the Fragile X community,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We are thankful for our ongoing constructive dialogue with the FDA on our path forward to NDA submission. Completing the development of Zygel in FXS and preparing for a successful launch will be the primary focus of the Company.”

Financial Impact on Cash
The Company expects that its cash runway will extend into the beginning of 2023 as a result of these changes to its development plans.

Conference Call Information
Zynerba management will host a live conference call and webcast today at 8:30 am Eastern Time to discuss the recent FDA meeting and the regulatory pathway for Zygel in FXS. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 4088027. 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 Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in 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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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 and 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 planned clinical trial evaluating Zygel™ in patients with a highly methylated FMR1 gene may not confirm the results of the CONNECT-FX trial or may not be determined to be sufficient to support an NDA submission; 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 timing and outcome of current and future legal proceedings; and 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. 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.

Investor Contact
William Roberts, Vice President, Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489

– New Efficacy Data Describe Strong Evidence of Seizure Reduction over 12 Months of Treatment, Including a 73% Median Reduction from Baseline in Monthly Seizure Frequency at Month 12 –

– Zygel™ Improves the Profound Sleep Disturbance Often Experienced by Developmental and Epileptic Encephalopathy (DEE) Patients Enrolled in the BELIEVE Trial – 

Devon, PA, December 4, 2020 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, is presenting two posters describing the efficacy, safety and quality of life results of the Phase 2 BELIEVE (Open Label Study to Assess the Safety and Efficacy of Zygel™ (ZYN002) Administered as a Transdermal Gel to Children and Adolescents with Developmental and Epileptic Encephalopathy) clinical trial at the 2020 virtual annual meeting of the American Epilepsy Society (AES). Both posters are available on the Zynerba corporate website at http://zynerba.com/publications/.

“These newly reported data are exciting as they describe the compelling anti-seizure activity of Zygel in children and adolescents suffering from developmental and epileptic encephalopathies, or DEEs, through twelve months of treatment,” said Zynerba’s Chief Medical Officer, Joseph M. Palumbo, MD, FAPA, MACPsych. “This is particularly exciting, as this trial was conducted in a refractory seizure population in which patients failed to show adequate response despite taking as many as four anti-seizure drugs. Additionally, we observed an equally compelling seizure reduction in children with a coexisting diagnosis of autism spectrum disorder.”

The first poster entitled, “ZYN002 Cannabidiol Transdermal Gel in Children and Adolescents With Developmental and Epileptic Encephalopathies: An Open-Label Clinical Trial [BELIEVE (ZYN2-CL-025)]” describes the evidence of tolerability and efficacy of Zygel observed in children and adolescents with developmental and epileptic encephalopathies (DEE) who participated in the Phase 2 BELIEVE trial treated for up to 12 months.

As shown in Figure 1, new results presented today include 12-month treatment data showing improvements in the median percentage reduction from baseline in monthly frequency of consciousness-impairing seizures (focal impaired awareness seizures, or FIAS, and tonic-clonic seizures, or TCS, including generalized tonic-clonic seizures [GTCS] and focal to bilateral tonic-clonic seizures [FBTCS]), ranged from 44% at month three to 73% at month 12.

Figure 1: Median Percentage Reduction From Baseline in 28-Day Frequency of FIAS and TCS by Time Point, Patients With FIAS and/or TCS at Baseline

When analyzed by seizure type, median reductions from baseline at month six for FIAS, GTCS, and FBTCS were 45%, 60%, and 59%, respectively. At month 12, the median reductions for FIAS, GTCS and FBTCS were 100%, 83% and 59% respectively.

Additionally, as shown in Figure 2, a substantial percentage of patients achieved ≥35% and ≥50% reduction in FIAS and TCS by month three (58% and 46%, respectively), and these reductions in seizures continued through month 12 (89% and 83%, respectively).

Figure 2: Percentage of Patients With 35% and 50% Reduction in FIAS and TCS by Time Point, Patients With FIAS and/or TCS at Baseline

Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired social-communication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder (ASD)[1]. Zynerba conducted an exploratory analysis to evaluate the efficacy of Zygel in reducing seizures in DEE patients with coexisting ASD enrolled in BELIEVE.

As seen in Figure 3, over the 12-month treatment period, the median percentage reduction from baseline in monthly frequency of consciousness-impairing seizures (FIAS or TCS) in patients with DEE and ASD improved over time, and these reductions in seizures ranged from 45% at month three to 74% at month 12.

Figure 3. Median Percentage Reduction From Baseline in 28-Day Frequency of FIAS and TCS by Time Point, Patients With Coexisting ASD at Baseline

As seen in Figure 4, a substantial percentage of patients achieved ≥35% and ≥50% reduction in FIAS and TCS by month three (60% and 40%, respectively), and these reductions continued through month 12 (75%).

Figure 4: Percentage of Patients With 35% and 50% Reduction in FIAS and TCS by Time Point, Patients With Coexisting ASD at Baseline

Zygel was well tolerated in BELIEVE. Most treatment-emergent adverse events (any event, whether unrelated or related to study drug) were mild or moderate. There were no clinically significant changes in vital signs, ECGs, or laboratory findings except for one patient with a transient, benign, isolated elevation of alkaline phosphatase at week 26 that was not considered related to study medication.

The authors of the poster concluded that: 

• These data suggest meaningful reductions in FIAS and TCS with Zygel treatment which is maintained through to 12 months of treatment with Zygel;
• In the subgroup of patients with ASD, Zygel demonstrated meaningful reductions in FIAS and TCS seizures, with most children reaching either the 35% or 50% responder threshold by month three and month six respectively;
• Zygel was well tolerated over 18 months of treatment in a medically fragile patient population of children and adolescents with DEEs; and
• The positive benefit/risk profile of Zygel in this trial supports further study in patients with DEEs and FIAS and TCS.

The second poster entitled, “Quality of Life and Sleep Assessments in Children with Developmental and Epileptic Encephalopathies Treated With ZYN002 (CBD) Transdermal Gel: BELIEVE (ZYN2-CL-025)” describes the impact of Zygel on profound sleep disturbances experienced by DEE patients enrolled in the BELIEVE trial. 

Dr. Palumbo continued, “These new data highlight the impact Zygel has on the profound sleep disturbance often experienced by DEE patients in this trial. Importantly, disrupted sleep in children with epilepsy has previously been reported to be associated with negative outcomes in overall family functioning. The Sleep Disturbance Scale for Children (SDSC) utilized in the BELIEVE trial shows that half of the enrolled children exhibited clinically significant sleep problems at study baseline, which improved while receiving Zygel.”

The Sleep Disturbance Scale for Children (SDSC) is a 26-item scale completed by caregivers that assesses six different sleep categories. The authors of the poster concluded that treatment with Zygel may be associated with improvements in disorders of initiating and maintaining sleep, disorders of arousal/nightmares, sleep wake transitions, and overall sleep, as well as clinically meaningful improvements observed in vitality, cognition/concentration, socially avoidant behaviors, seizure severity, behavior, and mood.

As shown in Figure 5 and Table 1 below, statistically significant improvements from baseline in sleep scores were observed in the Total Sleep Score (p=0.012), Disorders of Initiating or Maintaining Sleep (DIMS; p=0.006), Disorder of Arousal/Nightmares (DA; p=0.031), and Sleep Wake Transition Disorder (SWTD; p=0.030).

Figure 5: The Sleep Disturbance Scale for Children (SDSC) – Percentage of Patients Above Threshold for Clinically Significant Sleep Problems at Baseline and Week 26

Table 1. Change From Baseline in the SDSC

Notes
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481888/

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in 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, autism spectrum disorder, 22q11.2 deletion syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. 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 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 and 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 timing and outcome of current and future legal proceedings; and 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. 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 Contact
Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com

Media Contact
Molly Devlin
Evoke KYNE
215.928.2199
Molly.Devlin@evokegroup.com