Author: Jennifer Guinan

– Topline Results from BRIGHT Study Expected in the Second Quarter of 2020 –

Devon, PA., January 13, 2020 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced the achievement of its enrollment target for the 14-week Phase 2 BRIGHT (An Open-Label Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Autism Spectrum Disorder) trial of Zygel™ for the treatment of pediatric and adolescent patients with autism spectrum disorder (ASD). The Company expects to announce topline results from this study in the second quarter of 2020.

“We are committed to developing new treatment options to improve outcomes in patients suffering from a variety of neuropsychiatric conditions including autism spectrum disorder and achieving our enrollment target in the BRIGHT trial is an especially meaningful step toward this goal,” said Joseph M. Palumbo, MD, FAPA, MACPsych, Chief Medical Officer of Zynerba. “We would like to thank everyone involved in this study to date, particularly the participating patients and their caregivers, as well as the investigators. We look forward to announcing topline results from this study in the second quarter of 2020.”

The 14-week exploratory Phase 2 BRIGHT trial has enrolled 36 patients with ASD at a single clinical site in Australia. The trial is designed to evaluate the efficacy and safety of Zygel in children and adolescents (ages four through 17) with ASD as confirmed by DSM-5 diagnostic criteria for ASD. Enrolled patients are receiving weight-based initial doses of 250 mg daily or 500 mg daily of Zygel. The efficacy assessments include the Aberrant Behavior Checklist (ABC), Parent Rated Anxiety Scale – Autism Spectrum Disorder (PRAS-ASD), Autism Impact Measure (AIM), the Children’s Sleep Habit Questionnaire (CSHQ), and Clinical Global Impression – Severity and Improvement (CGI-S, CGI-I). After completing dosing in the 14-week period, participants may enroll in a six-month extension trial.

Using the Autism Diagnostic Observation Schedule (ADOS-2) which is administered at baseline by a qualified clinician, 94% of enrolled patients had moderate-to-severe symptoms of ASD at baseline. The mean baseline ABC-C Irritability subscale score of 30.0 further supports the severity of the enrolled patient population. Thirty-three (92%) are male. The mean age of these patients is 9.3 years.

About Autism Spectrum Disorder (ASD)
Autism Spectrum Disorder is a developmental disorder that affects communication and behavior in approximately one million pediatric and adolescent patients between the ages of five and 17 in the U.S. It refers to a range of conditions characterized by anxiety, repetitive patterns of behavior, impairments in social communication including verbal and non-verbal communication, and deficits in developing and maintaining relationships. Although autism can be diagnosed at any age, it is said to be a “developmental disorder” because symptoms generally appear in the first two years of life. Research suggests that genes can act together with influences from the environment to affect development in ways that lead to ASD. Newer studies suggest that ASD is linked to disruption in the endocannabinoid system.

About Zygel™
Zygel (cannabidiol [CBD] gel) is the first and only pharmaceutically-manufactured CBD 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 Fragile X syndrome (FXS) and other neuropsychiatric conditions including ASD may be associated with a disruption in the endocannabinoid (EC) system. Clinical and anecdotal data suggest that CBD may modulate the EC system and improve certain core social and behavioral autism-related symptoms, including social avoidance and anxiety.

Zygel is being studied in clinical trials in a number of rare and near-rare neuropsychiatric conditions. Target enrollment has been achieved in the Phase 2 BRIGHT trial of Zygel in ASD, with topline data anticipated in the second quarter of 2020. Enrollment is ongoing in CONNECT-FX, a multi-national, randomized, double blind, placebo-controlled pivotal clinical trial of Zygel in Fragile X syndrome (https://www.connectfxtrial.com/) and in the Phase 2 INSPIRE trial in 22q11.2 deletion syndrome. Zynerba also expects to meet with the U.S. Food and Drug Administration in the first half of 2020 to discuss the recently announced positive topline safety and efficacy data from its Phase 2 BELIEVE 1 clinical trial in patients with developmental and epileptic encephalopathies, and the clinical path forward.

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. For example, there can be no guarantee that the Company will obtain approval for Zygel from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if Zygel is approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. 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 FDA 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; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. 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
William Roberts, Vice President, Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489

robertsw@zynerba.com  

Devon, PA, November 12, 2019  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that the U.S. Patent and Trademark Office has issued US Patent No. 10,471,022, titled “Treatment of Fragile X Syndrome with Cannabidiol” which includes claims directed to a method of treating Fragile X syndrome, comprising transdermally administering 250 mg or 500 mg of cannabidiol (CBD) daily via a gel or cream.

This new patent, which expires in 2038, is part of an expanding intellectual property portfolio covering the Company’s transdermal CBD product candidate, Zygel™ (ZYN002 CBD gel).

Zygel is currently being studied in CONNECT-FX, a pivotal, multi-national, randomized, double blind, placebo-controlled study evaluating the efficacy and safety of Zygel in 204 three through 17-year old FXS patients with full mutation of the FMR1 gene. The primary endpoint is the change from baseline to the end of the treatment period in the Aberrant Behavior Checklist-Community FXS Specific (ABC-C_FXS) Social Avoidance subscale. Patients who have completed the double-blind phase are now enrolling into the 12-month open label phase. The Company expects to report top line data in the first half of 2020.

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. For example, there can be no guarantee that the Company will obtain approval for ZYN002 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated.  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 success and timing of the Company’s product development activities, studies and clinical trials and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. 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
robertsw@zynerba.com

– Topline Results from Pivotal Trial in Fragile X Syndrome On Track for 1H2020 –

– Positive Topline Results from BELIEVE 1 Phase 2 Trial of Zygel™ in Children and Adolescents with Developmental and Epileptic Encephalopathies Suggest Compelling Seizure Reductions and Excellent Tolerability –

– Phase 2 Topline Results in Autism Spectrum Disorder and 22q11.2 Deletion Syndrome On Track for 1H2020 –

Devon, PA, November 6, 2019 — 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 third quarter ended September 30, 2019 and provided an overview of recent operational highlights.

“The third quarter of 2019 was a remarkable period of progress and execution for Zynerba,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We announced compelling topline safety and efficacy results from our six month BELIEVE Phase 2 trial of Zygel™ in childhood epilepsies. In this study, patients experienced median reductions in their most common and debilitating seizures of 44% or more starting at month two and continuing through month six. In this medically fragile patient population, and consistent with our prior trials, Zygel was very well tolerated. Caregivers also reported important improvements in seizure intensity and duration in their children, and in socio-behavioral and cognitive impairments that are common in this population. Finally, we continued to progress towards full enrollment in our pivotal CONNECT-FX trial in children and adolescents with Fragile X syndrome, and expect to announce topline results in the first half of next year.”

Third Quarter 2019 Highlights

Zygel in Developmental and Epileptic Encephalopathies (DEE)

Presented Positive Topline Efficacy and Tolerability Results from BELIEVE 1 Open Label Phase 2 DEE Study

The topline results of this six month Phase 2 evaluation of Zygel in 48 children and adolescents with various DEEs showed meaningful reductions in seizures and excellent tolerability. Patients experienced 44% to 58% monthly median reductions in focal impaired-awareness seizures (FIAS; previously known as complex partial seizures) and/or convulsive seizures (CS; focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures), the most common and debilitating seizure types, starting at month two and continuing through month six. In addition, 42% to 63% of patients experienced a ≥50% monthly reduction in these seizures. Children with DEE are medically fragile, and as such, adverse events (all events, whether unrelated or related to study drug, that occur during the trial period) are common and expected. Only ten patients experienced a serious adverse event (SAE). Of those ten, eight were deemed to be unrelated to drug and only two were deemed possibly related to study drug, including one case of lower respiratory tract infection and one case of status epilepticus, both of which are common events in this patient population. There were no drug-related hepatic, gastrointestinal, or lethargy-related SAEs observed during this study.

Presented Qualitative Data Evaluating the Impact of Zygel on Quality of Life of Children with DEE

As part of the BELIEVE 1 study, caregivers were asked to provide a qualitative assessment regarding their child’s overall experiences during treatment with Zygel. Caregiver feedback to a series of open-ended questions was collected and coded by two independent reviewers. These qualitative assessments indicated improvements in alertness, awareness, or energy (58% of caregivers); seizures (51% of caregivers); cognition/concentration (47% of caregivers); socially-avoidant behaviors (44% of caregivers); and school attendance (28% of caregivers).

Preparations Underway for First Half 2020 Meeting with U.S. Food and Drug Administration (FDA) to Discuss Pathway for Zygel in DEE

Zynerba intends to meet with the FDA in the first half of 2020 to discuss the clinical path forward in DEE. Based on the Phase 2 trial design and results, the Company anticipates that it will discuss the pursuit of an indication that includes all syndromes and encephalopathies in the DEE category that present with FIAS and/or CS, the most common and debilitating seizure types representing 75% to 80% of all seizures.

Zygel in Fragile X Syndrome (FXS)

Fragile X Syndrome Pivotal Data Expected in the First Half of 2020

Enrollment is progressing in CONNECT-FX, a pivotal, multi-national, randomized, double blind, placebo-controlled trial evaluating the efficacy and safety of Zygel in treating common behavioral symptoms of FXS in three through 17-year old patients with FXS. The Company expects to report top line results in the first half of 2020. The primary endpoint is the change from baseline to the end of the treatment period in the Aberrant Behavior Checklist-Community FXS Specific (ABC-C_FXS) Social Avoidance subscale. Key secondary endpoints are the change from baseline to the end of the treatment period in the ABC-C_FXS Irritability subscale score, the ABC-C_FXS Socially Unresponsive/Lethargic subscale score, and improvement in Clinical Global Impression – Improvement (CGI-I) at the end of the treatment period. If the results are positive, the Company expects to submit its New Drug Application (NDA) for Zygel in FXS to the U.S. Food and Drug Administration (FDA) in the second half of 2020, with potential approval by mid-year 2021.

Poster Further Validating the Use of the ABC-C_FXS Presented at the 22^nd Society for the Study of Behavioural Phenotypes (SSBP) Symposium

The poster described data collected via web-based journals and in-depth interviews of caregivers of children with FXS. The data indicate that nine of ten caregivers (90%) reported that their children had behaviors representative of social avoidance, socially unresponsiveness/lethargic, and irritability and that the described behaviors had strong concordance with individual domains of the ABC-C_FXS. We believe that these data help elucidate the most common core behaviors of FXS, and further validate the appropriateness of the ABC-C_FXS as an effective tool for use in clinical studies as a means to measure improvements in these core and common FXS behaviors.

Zygel 12-week Open Label Phase 2 FXS Data Published in the Journal of Neurodevelopmental Disorders

The results of the Phase 2 FAB-C clinical trial have been published in the peer-reviewed Journal of Neurodevelopmental Disorders in a paper entitled, ‘A Phase 1/2, Open Label Assessment of the Safety, Tolerability, and Efficacy of Transdermal Cannabidiol (ZYN002) for the Treatment of Pediatric Fragile X Syndrome’ (Heussler, Helen; Cohen, Jonathan; Silove, Natalie, et al.).

Zygel in Autism Spectrum Disorder (ASD)

Phase 2 Open Label Trial of Zygel in ASD Ongoing; Data Expected in the First Half of 2020

The Company is conducting the Phase 2 BRIGHT trial to assess the safety, tolerability and efficacy of Zygel for the treatment of child and adolescent patients with ASD. The 14-week trial is designed to evaluate the efficacy and safety of Zygel in approximately 36 children and adolescents (ages four through 17) with ASD as confirmed by DSM-5 diagnostic criteria for ASD. The efficacy assessments include the Aberrant Behavior Checklist, Parent Rated Anxiety Scale – Autism Spectrum Disorder, Autism Impact Measure, and Clinical Global Impression – Severity and Improvement. Zynerba expects to report topline results from this study in the first half of 2020.

Poster Describing the Shared Sociobehavioral Symptoms in ASD, FXS, and 22q11.2 Deletion Syndrome Presented at the 22^nd SSBP Symposium

The poster described the results of a retrospective literature review on patients with ASD, FXS, and 22q11.2 deletion syndrome (22q) conducted to determine symptomatic overlap between these disorders. The data indicate that patients with ASD, FXS, and 22q share a constellation of sociobehavioral symptoms and that the pharmacology of CBD is broad, continues to be defined, and may prove to be beneficial in addressing important behavioral symptoms of these conditions.

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

Phase 2 Open Label Trial of Zygel in 22q Ongoing; Data Expected in the First Half of 2020

The Company is conducting the 14-week Phase 2 INSPIRE trial to evaluate the safety, tolerability and efficacy of Zygel in approximately 20 children and adolescents (ages six through 17) with genetically-confirmed 22q. The efficacy assessments include the Aberrant Behavior Checklist-Community (ABC-C), the Anxiety, Depression and Mood Scale (ADAMS), the Qualitative Caregiver Reported Behavioral Problem Survey, and Clinical Global Impression – Severity and Improvement. Zynerba expects to report topline results from this study in the first half of 2020.

Third quarter 2019 Financial Results

Our Australian subsidiary, Zynerba Pharmaceuticals Pty Ltd, or the Subsidiary, is incorporated in Australia and is eligible to participate in an Australian research and development tax incentive program.  As part of this program, the Subsidiary is eligible to receive a cash refund from the Australian Taxation Office for a percentage of the research and development costs expended by the Subsidiary in Australia. In July 2019, the Australian government’s Department of Industry, Innovation and Science, or AusIndustry, responded to an Advance Overseas Finding, or AOF, application submitted by Zynerba that will allow certain research and development expenses incurred with respect to our product candidate Zygel outside of Australia to be eligible for the Australian research and development tax incentive program. As a result of this finding, we are eligible to receive a cash refund from the Australian Taxation Office for the qualifying research and development costs expended outside of Australia in 2018, 2019 and 2020. During the three months ending September 30, 2019, we recorded an $8.3 million credit to research and development expenses for amounts expected to be received through the AOF for the period from January 1, 2018 through September 30, 2019. Although the AOF approval extends into 2020, management believes that substantially all qualifying amounts have been recorded as of September 30, 2019.

The following table summarizes research and development expenses for the three months ended September 30, 2019 and 2018.

Excluding the $8.3 million reduction in research and development expenses for amounts expected to be received through the AOF for the period from January 1, 2018 through September 30, 2019, research and development expenses increased by $1.8 million to $6.7 million for the three months ended September 30, 2019 from $4.9 million for the three months ended September 30, 2018. The increase was primarily related to an increase in clinical trial and manufacturing costs related to our Zygel program. Stock based compensation included in the R&D costs were $0.6 million.

General and administrative expenses for the third quarter of 2019 were $3.5 million, including stock-based compensation expense of $0.8 million.

The net loss for the third quarter of 2019 was $1.9 million with basic and diluted net loss per share of $(0.08).

Financial Outlook

The Company’s cash and cash equivalent position as of September 30, 2019 was $77.5 million. Management believes that the cash and cash equivalent position is sufficient to fund operations and capital requirements beyond the expected NDA submission and potential approval of Zygel in FXS and into the second half of 2021.

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; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. 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

(unaudited)

ZYNERBA PHARMACEUTICALS, INC.

CONSOLIDATED BALANCE SHEETS

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

Will Roberts, VP Investor Relations and Corporate CommunicationsZynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

Devon, PA, October 25, 2019  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that Zynerba’s Vice President of Communications and Investor Relations, Will Roberts, will present a company overview at the Dawson James Securities 5th Annual Small Cap Growth Conference. The presentation will take place on Tuesday, October 29^th at 9:40AM EDT at the Wyndham Grand Jupiter. A live webcast of the presentation will be accessible on the Investor Relations page of http://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
William Roberts, Vice President, Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com 

Devon, PA, September 26, 2019  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that Zynerba’s Chief Executive Officer, Armando Anido will present a company overview at the 2019 Cantor Global Healthcare Conference. The presentation will take place on Thursday October 3^rd at 8:55 AM EDT at the InterContinental New York Barclay. A live webcast of the presentation will be accessible on the Investor Relations page of http://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
William Roberts, Vice President, Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com 

– Study Achieves a 44% Median Seizure Reduction in Focal Impaired Awareness (Complex Partial) and Convulsive Seizures in DEE Patients by Month Two; Reductions were Sustained through Month Six of Treatment with Zygel –

– At Least 42% of these Patients Experienced a ≥50% Improvement from Month Two through Month Six –

– Qualitative Assessments Demonstrate Improvements in Seizure Intensity and Duration, and Socio-behavioral and Cognitive Impairments –

Devon, PA, September 18, 2019  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced positive top line results from the open label Phase 2 BELIEVE 1 (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. The trial assessed the safety and efficacy of Zygel in developmental and epileptic encephalopathies (DEE), a heterogeneous group of rare pediatric epilepsy syndromes, including Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). DEE is characterized by the presence of multiple focal and generalized seizure types and severe cognitive and behavioral impairment. The most common and debilitating seizure types in people with epilepsy are focal impaired-awareness and convulsive seizures. Patients who experienced these seizure types achieved 44% to 58% monthly median reductions in seizures compared to baseline from month two to month six of treatment with Zygel. Further, qualitative assessments by caregivers in the study demonstrate that use of Zygel may result in improved socio-behavioral and cognitive symptoms of DEE. Zygel was also well tolerated in this study.

“The data from the BELIEVE 1 clinical trial are promising and suggest that Zygel may reduce seizure frequency in many types of difficult to treat developmental and epileptic encephalopathies and improve important behavior deficits, alertness, social interactions, and enable the child to be well enough to attend school more consistently,” said Ingrid Scheffer, AO, MBBS, PhD, FRACP, Professor and Chair, Paediatric Neurology Research, The University of Melbourne, and an investigator in the BELIEVE 1 trial. “DEE are the most challenging and poorly controlled epilepsy disorders with many symptoms that adversely affect patient and family function. I believe that this drug holds promise as a potential treatment for DEE.”

“We are encouraged by the positive top line results of the BELIEVE 1 trial of Zygel in children and adolescents with DEE, and we believe these data represent an important step forward for these patients and their families,” said Armando Anido, Zynerba’s Chairman and Chief Executive Officer. “These results suggest that Zygel may produce clinically meaningful reductions in seizures and may improve many of the difficult behaviors and symptoms, such as seizure intensity, fatigue, social isolation, poor cognition, and language deficits. Once we complete our analyses of the data, we intend to seek a meeting with the FDA, likely in the first half of next year, to discuss the clinical pathway to approval.”

Study Design

The six-month BELIEVE 1 clinical trial is an exploratory open label multi-dose Phase 2 clinical trial designed to evaluate the safety and efficacy of Zygel in children and adolescents (three to <18 years) with DEE as classified by the International League Against Epilepsy (ILAE) (Scheffer et al. 2017). Forty-eight patients with confirmed DEE were enrolled in the clinical trial and are included in the safety data for the trial. Forty-six patients are included in the modified intent-to-treat population (mITT). The two patients excluded from the intent-to-treat population included one patient who did not complete 80% of their seizure diaries and a second patient who did not complete a minimum of eighty days of treatment. Enrolled patients received weight-based initial doses of 250 mg or 500 mg daily of Zygel. Patients could be titrated up to 1,000 mg daily.

Baseline Patient Demographics

The BELIEVE 1 trial enrolled 48 patients between the ages of three and 16 (mean=10.5; median=10.0). Fifty-four percent of patients were male, and 46% were female. Patients weighed between 14.3 and 110 kilograms (mean=39.3; median=36.1). Patient BMI ranged between 12.5 and 35.4 (mean=19.2; median=18.6).

Top-line Efficacy Results

Of the 46 patients in the mITT population, 33 (72%) had focal impaired-awareness seizures (FIAS; previously known as complex partial seizures) and/or convulsive seizures (focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures) at baseline. These patients experienced a mean baseline seizure count of 64 FIAS and/or convulsive seizures, and a median baseline seizure count of 8.2 FIAS and/or convulsive seizures. Compared to baseline seizure frequency, these patients experienced a ≥44% median reduction in seizures from month two onwards using monthly seizure frequency normalized to 28 days (SF28).

Fifty-five percent (55%) of patients with FIAS and/or convulsive seizures experienced a ≥50% median reduction in seizures at month six of treatment with Zygel.

FIAS and convulsive seizures	Month 1 (n=33)	Month 2 (n=33)	Month 3 (n=33)	Month 4 (n=32)	Month 5 (n=32)	Month 6 (n=29)
Median % reduction in seizure frequency	16%	44%	44%	47%	58%	51%
≥50% responder rate	30%	42%	46%	47%	63%	55%

Thirteen of the 46 patients had a variety of non-FIAS and non-convulsive seizure types at baseline. The number of individual seizure types in these patients was too small to draw definitive conclusions and further analyses are warranted. 

Patients with either DS or LGS who experienced FIAS and/or convulsive seizures (n=11) experienced a 51% median reduction in FIAS and/or convulsive seizures at month six of treatment compared to baseline. Sixty percent (60%) of patients with DS or LGS experienced a ≥50% median reduction in FIAS or convulsive seizures at month six of treatment with Zygel.

Lennox-Gastaut and Dravet syndromes	Month 1 (n=11)	Month 2 (n=11)	Month 3 (n=11)	Month 4 (n=11)	Month 5 (n=11)	Month 6 (n=10)
Median % reduction in seizure frequency	18%	6%	46%	23%	63%	51%
≥50% responder rate	36%	36%	46%	40%	64%	60%

Safety data

Zygel was well tolerated, and the safety profile was consistent with previously released data from Zygel clinical trials. Eight patients discontinued the study; one discontinued as a result of an application site reaction, and seven discontinued as a result of withdrawal of consent or perceived lack of efficacy. Through six months of therapy, ninety-six percent (96%) of patients experienced a treatment emergent adverse event (TEAE) and 60% of patients experienced a treatment related adverse event. Most were mild to moderate. The most common treatment related adverse events (in >5% of patients) are application site dryness (8.3%), application site pain (8.3%), and somnolence (8.3%). Ten patients reported a serious adverse event (SAE); most were infection-related. Two SAEs (lower respiratory tract infection and status epilepticus) were determined to be possibly related to treatment. There were no patient deaths during the study.

Qualitative analysis of the impact of Zygel on behavioral and cognitive symptoms

Parents and caregivers were asked to provide a qualitative assessment regarding their child’s overall experiences during treatment with Zygel. The experiences of 43 patients are summarized below.

• 58% reported improved vitality (e.g. alertness / awareness, energy)
• 51% reported improvement in seizures
• 47% reported improved cognition and concentration
• 44% reported improved socially avoidant behaviors
• 28% reported that their child attended school on time / more often
• 26% reported difficulty in application of the gel to their child (e.g. time it takes for gel to dry)

About Developmental and Epileptic Encephalopathies (DEE)
DEE is a heterogeneous group of epilepsy syndromes that may be associated with severe cognitive impairment and behavioral disturbances. These disorders are often progressive, and are highly resistant to treatment. DEE includes a number of rare and ultra-rare epilepsy syndromes including early myoclonic encephalopathy, epileptic encephalopathy with continuous spike and wave during sleep, and certain syndromes including Ohtahara, West, Landau-Kleffner, Lennox-Gastaut, Doose and Dravet. Improved seizure control may have a positive impact on development and quality of life.

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. For example, there can be no guarantee that the Company will obtain approval for Zygel from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if Zygel is approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. 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 FDA 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; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. 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
William Roberts, Vice President, Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

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

– Preliminary Evidence Shows that CBD May Prove to be Effective in Managing the Spectrum of Behavioral Symptoms Associated with these Conditions –

– New Data Presented Today at the Society for the Study of Behavioural Phenotypes (SSBP) Research Symposium –

Devon, PA, September 5, 2019  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, is presenting data today describing the results of a retrospective literature review on patients with autism spectrum disorder (ASD), Fragile X syndrome (FXS), and 22q11.2 deletion syndrome (22qDS) conducted to determine symptomatic overlap between these disorders. The data indicate that patients with ASD, FXS, and 22qDS share a constellation of sociobehavioral symptoms and that the pharmacology of CBD is broad, continues to be defined, and may prove to be beneficial in addressing important behavioral symptoms of these conditions.

The poster, entitled Common Behavioral Features of Autism, Fragile X Syndrome, and 22q11.2 Deletion Syndrome, is being presented on September 5^th and 6^th at the 22^nd Society for the Study of Behavioural Phenotypes (SSBP) Research Symposium at Aston University in Birmingham, UK. A copy of the poster is available on the Zynerba corporate website at http://zynerba.com/publications/.

Honey Heussler, MBBS, FRACP, MRCPCH, PGCAP, DM, Associate Professor, University of Queensland and Medical Director Child Development, Children’s Health Queensland is presenting data showing that patients with ASD, FXS, and 22qDS share a constellation of sociobehavioral symptoms that includes anxiety, which may lead to social avoidant behavior, aggression, irritability, attention deficits, and poor communication. Dr. Heussler is presenting the poster from 12:40 – 1:45 British Summer Time (BST) on September 5^th and 6^th, 2019.

“Those of us who care for patients and families contending with certain neuropsychiatric dysfunction understand that there are significant shared sociobehavioral symptoms between such disorders, though until now no review has been conducted to examine or clarify the overlap,” said Dr. Heussler. “These data on the shared behaviors between ASD, FXS and 22qDS are important to understanding disease impact, patient care, and the development of potential treatments. One such potential treatment being studied in well-controlled clinical trials is a proprietary gel formulation of CBD, which has diverse pharmacologic effects and may prove to be important in these neuropsychiatric disorders.”

Based on insights from Company data, a search of the PubMed database was conducted using the terms “behavior,” “behavioral symptoms,” “autism spectrum disorder,” “ASD,” “Fragile X Syndrome,” “FXS,” “22q11.2 deletion syndrome,” “parents,” “caregivers,” and “CBD and treatment of anxiety” with no restriction on date or publication type. Records were then analyzed for relevance. The most common behavioral manifestations across all conditions are anxiety-related, such as social avoidance, aggression, irritability, attention deficits, stereotypy, poor communication, and social unresponsiveness.

ASD

Anxiety-related symptoms are common in patients with ASD with up to 84% of children experiencing some degree of debilitating anxiety. Rates of physician-diagnosed anxiety disorders in these patients range from 42% to 55% and may include simple phobias, generalized anxiety disorder, separation anxiety disorder, obsessive-compulsive disorder, and social phobias. Comorbid anxiety disorders can be associated with behaviors such as aggression/irritability and isolation from same-age peers (due to bullying/victimization in school). Inattention and hyperactivity are often present in Attention Deficit-Hyperactivity Disorder and ASD.

FXS

In FXS, severe cognitive and social impairments are more common in males than in females. FXS usually has profound effects on the life of patients (comorbid conditions, social impairment) as well as their caregivers and families (mental health, absence from work/school). Anxiety and social avoidance are considered core features of FXS; further, anxiety can be thought of as a foundational precipitant to social avoidance. Social avoidance encompasses behaviors that may include seeking isolation, lack of interaction, social escape, and gaze avoidance that distance the individual from his/her social counterparts.

22qDS

The most common behavioral/psychiatric diagnoses in children with 22qDS were ADHD, ASD, and anxiety. Up to one-third of patients with 22qDS will develop schizophrenia or schizo-affective disorder by late adolescent and early adulthood. The emergence of social deficits during adolescence can represent a major source of disability in some individuals with 22qDS. Cross-sectional studies (observational research that analyzes data collected at one given point of time across a sample population) show that children with 22qDS are withdrawn and shy, and have social impairments which may be less of a concern to the individual.

The Potential Role of CBD in Managing Behavioral Symptoms Associated with ASD, FXS, and 22qDS
The authors conclude that preliminary evidence, including findings from the Phase 2 open-label FAB-C study in children and adolescents with FXS and a retrospective literature review based on insights from that Company data, shows that CBD improves social anxiety and associated behavioral manifestations suggesting that it may prove to be effective in managing the spectrum of behavioral symptoms associated with these conditions.

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 Administrationand 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; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. 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 Commissionand 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 
robertsw@zynerba.com 

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

– Ninety Percent of Interviewed Caregivers Reported Social Avoidant, Irritability, and Socially Lethargic Behaviors in their Children with FXS –

– New Data Presented Today at the Society for the Study of Behavioural Phenotypes (SSBP) Research Symposium –

Devon, PA, September 5, 2019 — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, is presenting data today evaluating the Social Avoidance, Irritability, and Socially Unresponsive/Lethargic subscales of the Aberrant Behavior Checklist Community: FXS Specific (ABC-C_FXS) in relation to the experience of caregivers caring for a child with Fragile X syndrome. The poster describes data collected via web-based journals and in-depth interviews of caregivers of children with Fragile X syndrome (FXS). The data indicate that nine of ten caregivers reported their children had behaviors representative of social avoidance, socially unresponsiveness/lethargic, and irritability and the behaviors described had strong concordance with individual items of the ABC-C_FXS.

The poster, entitled Content Validity of the ABC-C_FXS and Subscales in Fragile X Syndrome, is being presented on September 5^th and 6^th at the 22^nd Society for the Study of Behavioural Phenotypes (SSBP) Research Symposium at Aston University in Birmingham, UK. A copy of the poster is available on the Zynerba corporate website at http://zynerba.com/publications/.

Terri Browning Sebree, Zynerba’s President, is presenting data providing qualitative evidence of the appropriateness of Social Avoidance, Irritability, and Socially Unresponsive/Lethargic subscales of the ABC-C_FXS in assessing core symptoms of FXS. In addition, the data further validate social avoidance, irritability, and socially unresponsive/lethargic behaviors as core FXS behavioral symptoms from the perspective of caregivers of children with the disorder. The Company is utilizing the ABC-C_FXS to assess improvements in core behaviors of FXS in the ongoing 14-week pivotal CONNECT-FX study of Zygel™ (CBD gel). Ms. Sebree will present the poster from 12:40 to 1:45 British Summer Time (BST) on September 5^th and 6^th, 2019.

“Fragile X syndrome is a complex diagnosis for a child and his/her family, marked by a myriad of specific behavioral and emotional symptoms often manifesting as anxiety and social avoidant behaviors,” said Ms. Sebree. “Through studies like this one, we are able to not only elucidate the most common core behaviors of FXS, but also further validate the appropriateness of the ABC-C_FXS as an effective tool for use in clinical studies as a means to measure improvements in these core and common FXS behaviors.”

Ten caregivers of children formally diagnosed with FXS participated in this study with assistance from the National Fragile X Foundation (NFXF) via online invitation through the NFXF website. The study found that 90% of caregivers reported at least one behavior that was representative of social avoidance, socially unresponsive/lethargic, and irritability

Social Avoidance

It was common for their children with FXS to prefer the company of single family members to groups of people, even friends, and to seek isolation from others either via physical setting (staying in their room or in the car) or blocking out the world (using headphones). Social avoidance had a negative impact on important activities, such as travel, schooling, or visits to the doctor.

The social-avoidant behaviors reported by caregivers, including ‘seeks isolation from others’, ‘prefers to be alone’, and ‘prefers solitary activities’ corresponded to items on the Social Avoidance subscale, including seeks isolation from others and isolates himself/herself from other children or adults

Irritability

Irritability was associated with a broad spectrum of verbal (talking back, hollering, articulate yelling, non-verbal screams) and physical behaviors (hitting siblings, overturning furniture) at inappropriate times.

Frequently reported aspects of misbehavior and irritability mapped onto items of the Irritability subscale, specifically ‘aggressive to others’, ‘irritability’, ‘temper tantrums/outbursts’, ‘screaming/yelling inappropriately’, ‘harming of others’, and ‘stubbornness’.

Socially Unresponsive/Lethargic

Caregivers frequently reported of ‘lack of interaction’ and ‘lack of attention’ in their children with FXS, which mapped to subscale items such as ‘preoccupied’, ‘stares into space’, ‘unresponsive to structured activities (does not react)’, and ‘shows few social reactions to others’. Items on the subscale pertaining to communication were identified as important by caregivers, particularly with respect to how they may exacerbate other syndrome-related behaviors.

The authors conclude that these data further validate social avoidance, irritability, and socially unresponsive/lethargic as core phenotypic behaviors of children with FXS and show that caregiver experiences correspond with ABC-C_FXS subscales, further validating the appropriateness of the ABC-C_FXS as an effective assessment tool in clinical trials.  

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 Administrationand 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; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. 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 Commissionand 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 
robertsw@zynerba.com 

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

Devon, PA, September 3, 2019  — Zynerba Pharmaceuticals, Inc.(NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that Zynerba’s Chief Executive Officer, Armando Anido will present a company overview at two upcoming conferences in New York City.

• The HC Wainwright 21^st Annual Healthcare conference on Monday September 9, 2019 at 9:10AM EDT at the Lotte New York Palace Hotel; and
• The Ladenburg Thalmann Healthcare Conference on Tuesday, September 24, 2019 at 2:30PM EDT at the Sofitel Hotel.

A live webcast of the presentations will be accessible on the Investor Relations page of http://www.zynerba.com. A replay of the webcasts will be available for 90 days following the conclusion of the event.

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
William Roberts, Vice President, Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489 
robertsw@zynerba.com

Devon, PA, August 29, 2019  — 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 22^ndSociety for the Study of Behavioural Phenotypes (SSBP) Symposium. The meeting is being held at Aston University in Birmingham, UK on September 4^th through 6^th, 2019. The posters will be viewable throughout September 5^th and 6^th and the authors will be available for additional discussion at the poster at the times noted below.

Poster title: “Content Validity of the ABC-C_FXS and Subscales in Fragile X Syndrome”
Author presentation time: 12:40PM – 1:45PM BST, September 5^th and 6^th, 2019
This poster will describe information evaluating the Social Avoidance, Irritability, and Socially Unresponsive/Lethargic subscales of the Aberrant Behavior Checklist Community: FXS Specific (ABC-C_FXS) in relation to the experience of caregivers caring for a child with Fragile X syndrome (FXS). In addition, the poster will describe the most common core FXS behaviors from the perspective of caregivers of children with the disorder.

Poster title: “Common Behavioral Features of Autism, Fragile X Syndrome, and 22q11.2 Deletion Syndrome”
Author presentation time: 12:40PM – 1:45PM BST, September 5^th and 6^th, 2019
Based on insights from Company data, Zynerba conducted a retrospective literature review on patients with autism spectrum disorder, FXS, and 22q11.2 deletion syndrome to determine the symptomatic overlap between these disorders and to determine a possible role for cannabidiol (CBD) in managing the spectrum of behavioral symptoms associated with these conditions. The poster will describe the results of this review.

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 StatementsThis 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.

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