Zynerba Pharmaceuticals to Host Conference Call to Provide Second Quarter 2018 Business Update

Devon, PA, July 31, 2018  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, will host a conference call at 8:30 am EDT on Thursday August 2, 2018 to provide its second quarter business and financial update following the recently completed public offering, which closed on July 24, 2018.  A press release announcing the results of the second quarter of 2018 will precede the conference call.

The call will begin at 8:30 am EDT on Thursday August 2, 2018, and will be accessible by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 9565578. The live webcast and replay will be made available on 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 and refractory epilepsies. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Investor Contact
Will Roberts, VP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

Zynerba Pharmaceuticals Announces Pricing of Public Offering of Common Stock

Devon, PA, July 20, 2018 — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE) today announced the pricing of an underwritten public offering of 4,062,500 shares of its common stock at a price of $8.00 per share, for a gross deal size of $32.5 million, before deducting underwriting discounts and commissions and other estimated offering expenses. In addition, Zynerba has granted the underwriters a 30-day option to purchase up to 609,375 additional shares of common stock at the public offering price, less underwriting discounts and commissions. The offering is expected to close on or about July 24, 2018, subject to the satisfaction of customary closing conditions.

Cantor Fitzgerald & Co. is acting as the sole book-running manager.

Zynerba intends to use the net proceeds of the proposed offering to support the clinical development of ZYN002, for additional research and development, and for general corporate purposes, which may include capital expenditures and funding our working capital needs.

The offering is being made by Zynerba pursuant to a shelf registration statement on Form S-3 previously filed with the Securities and Exchange Commission (the “SEC”) on June 9, 2017 and declared effective by the SEC on June 22, 2017. The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus related to the offering has been filed with the SEC and is available on the website of the SEC at www.sec.gov. When available, copies of the final prospectus supplement and accompanying prospectus may be obtained from Cantor Fitzgerald & Co., Attn: Capital Markets, 499 Park Avenue, 6th Floor, New York, NY 10022, by telephone at 212-829-7122 or by email at prospectus@cantor.com.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state or jurisdiction.

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 and refractory epilepsies.

Cautionary Statement Regarding 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 risks and uncertainties associated with market conditions and the satisfaction of customary closing conditions related to the proposed offering and the Company’s expectations regarding the use of proceeds therefrom. 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
Will Roberts, FP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7483
robertsw@zynerba.com

Zynerba Pharmaceuticals Announces Proposed Public Offering of Common Stock

Devon, PA, July 19, 2018  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE) today announced that it intends to offer and sell, subject to market conditions, shares of its common stock in an underwritten public offering.  All of the shares to be sold in the offering will be offered by Zynerba.  The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering. In addition, Zynerba intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of its common stock offered in the public offering.

Cantor Fitzgerald & Co. is acting as the sole book-running manager.

Zynerba intends to use the net proceeds of the proposed offering to support the clinical development of ZYN002, for additional research and development, and for general corporate purposes, which may include capital expenditures and funding our working capital needs.

The offering is being made pursuant to a shelf registration statement on Form S-3 previously filed with the Securities and Exchange Commission (the “SEC”) on June 9, 2017 and declared effective by the SEC on June 22, 2017. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement.  A preliminary prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC and will be available on the website of the SEC at www.sec.gov.  Copies of the preliminary prospectus supplement and the accompanying prospectus, when available, may also be obtained from Cantor Fitzgerald & Co., Attn: Capital Markets, 499 Park Avenue, 6th Floor, New York, NY 10022, by telephone at 212-829-7122 or by email at prospectus@cantor.com.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state or jurisdiction.

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 and refractory epilepsies.

Cautionary Statement 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 risks and uncertainties associated with market conditions and the satisfaction of customary closing conditions related to the proposed offering and the Company’s expectations regarding the completion, timing and size of its public offering and the use of proceeds therefrom. 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
Will Roberts, FP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7483
robertsw@zynerba.com

Zynerba Pharmaceuticals Announces New FAB-C Phase 2 Open-Label Data in Patients with Fragile X Syndrome

– Significant Improvements in Behavioral Symptoms Observed in Patients and Sustained through 38 Weeks of Treatment with ZYN002 –

– Presentation Today at the 16th NFXF International Fragile X Conference –

Devon, PA, July 12, 2018 — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, is reporting today new open label clinical data  in an oral presentation at the 16th NFXF (National Fragile X Foundation) International Fragile X Conference. The presentation will take place during the Industry Updates session at 4:30 PM EDT today in the Regency Ballroom of the Hyatt Regency, Cincinnati Ohio. A copy of the presentation and poster are available on the Zynerba corporate website at http://zynerba.com/publications/.

In a podium presentation entitled, “Transdermal Cannabidiol (CBD) Gel for the Treatment of Fragile X Syndrome (FXS),” Liza A. Squires, M.D., Zynerba’s Chief Medical Officer, will present new 12- and 38-week data describing significant and sustained improvements in behavioral symptoms with continued use of ZYN002 in children and adolescents with FXS. The presentation includes data through 38 weeks of treatment with ZYN002 in the open label Phase 2 FAB-C (Treatment of Fragile X Syndrome Anxiety and Behavioral Challenges with CBD) trial.

The data demonstrate that treatment with ZYN002 improved core behavioral symptoms of Fragile X syndrome with statistical significance versus baseline across multiple measures of efficacy at week 12, and these improvements were sustained through 38 weeks of treatment.  ZYN002 was well tolerated; no serious adverse events were reported, and no clinically meaningful trends in vital signs, ECG, or clinical safety laboratories, including liver function tests (LFTs), were observed.

“These data are consistent and compelling, and suggest that ZYN002 may have a clinically meaningful and durable effect on the most common observable behaviors associated with childhood and adolescent Fragile X syndrome,” said Honey Heussler, FRACP, DM, Associate Professor, University of Queensland and Medical Director Child Development, Children’s Health Queensland, and lead investigator in the FAB-C study. “The goal of an ideal therapeutic intervention is to reduce the severity and impact of these core symptoms, and thus improve the child’s ability to engage with the world around them, including with their parents, caregivers, teachers and peers. It is very encouraging that measurable improvements in behaviors were observed in this study across a variety of instruments, whether validated for use by caregivers or physicians. I am delighted by these data; however, we need the results from the recently initiated CONNECT-FX study for confirmation. I look forward to participating in the continued development of ZYN002 for these children.”

Study design
Twenty patients (3:1 males) aged 6 to 17 years of age (median = 9) with Fragile X were enrolled in the open label FAB-C study. All patients had genetic confirmation of the full mutation of the FMR1 gene. ZYN002 was added to other medications being administered. The first six weeks were designed to titrate dosing in patients. Dosing was initiated at 50 mg daily and could be increased to 250 mg daily. Weeks seven through 12 was a maintenance period where patients were treated at the dose established at week six. Two patients, who were siblings, discontinued during the initial 12-week period; one discontinued due to worsening eczema (not considered treatment related) and the other discontinued for administrative reasons. At the completion of week 12, 13 patients elected to enter into the extension study for up to 24 months.  To date, 12 patients remain in the study and have now exceeded 12 months of therapy with ZYN002.

Week 12 Efficacy
As previously disclosed, the 12-week FAB-C study achieved its primary endpoint, which was reduction in the Anxiety, Depression, and Mood Scale (ADAMS) total score from baseline to week 12 (n=18; 45.8% reduction; p<0.0001). Four of the five subscales of ADAMS also showed statistically significant reductions versus baseline.

Scale: ADAMS Baseline

(n=20)

Week 12

(n=18)

Week 12

% Improvement Group Mean

P-value vs Baseline
ADAMS Total Score 33.4 18.1 45.8 <0.0001
        General Anxiety 10.0 4.6 54.0 < 0.0001
        Social Avoidance 10.2 4.8 52.9 0.0002
        Compulsive Behavior 2.8 1.4 50.0 0.0262
         Manic/Hyperactive Behavior 9.4 6.1 35.1 0.0003
        Depressed Mood 2.8 2.0 28.6 0.1417

As previously disclosed, ZYN002 achieved statistically significant reductions in all six subscales of a secondary endpoint, the Aberrant Behavior Checklist – Community: FXS Specific (ABC-CFXS).

Scale: ABC-CFXS Baseline

(n=20)

Week 12

(n=18)

Week 12

% Improvement Group Mean

P-value vs Baseline
Stereotypy 7.9 3.2 59.5 0.0006
Social Avoidance 5.1 2.3 54.9 0.0005
Socially Unresponsive/Lethargic 8.7 4.1 52.9 0.0034
Inappropriate Speech 6.1 3.5 42.6 0.0018
Irritability 18.2 10.6 41.8 0.0096
Hyperactivity 14.5 9.8 32.4 0.0237

Zynerba is also releasing today the results of additional secondary efficacy endpoints that were evaluated in the first 12 weeks of the FAB-C trial, which the Company believes further reinforces the results from the ADAMS and ABC-CFXS , regardless of whether assessments were completed by a caregiver or physician. These measurements include:

Scale Baseline

(n=20)

Week 12

(n=18)

Week 12

% Improvement Group Mean

P-value vs Baseline
CGI-I n/a 2.5* n/a n/a
PARS-R 15.6 10.6 32.1 0.0006
PedsQL: Total 57.3 67.7 18.2 0.0100
VAS: Hyperactivity/Impulsivity 6.2 3.6 41.9  0.0002
VAS: Tantrum/Mood Lability 5.0 3.2 36.0 0.0023
VAS: Anxiety 6.2 3.8 38.7 0.0005
Vineland Adaptive Behavior 48.3 48.9 1.2 0.0472

* N=17 at week 12

The Clinical Global Impression Scale – Improvement (CGI-I) is a clinician-rated single-item 7-point scale that measures change in a patient’s condition following the start of a treatment. Ratings of one through three represent improvement; a rating of four represents no change; ratings of five through seven represent worsening of symptoms.

Long Term Efficacy: 12 and 38 Week
The following data show the improvement in various efficacy measures for the patients who completed 12 weeks, enrolled in the extension trial, and have completed 38 weeks of treatment.

Anxiety, Depression, and Mood Scale (ADAMS)

Scale: ADAMS Group Mean Percent Improvement from Baseline
Week 12

(n=12)

P-value vs Baseline Week 38

(n=12)

P-value vs Baseline
ADAMS Total Score 48.6 0.0001 59.2 <0.0001
     General Anxiety 55.1 <0.0001 58.2 <0.0001
     Social Avoidance 52.5 0.0013 61.6 0.0007
     Compulsive Behavior 50.0 0.0295 59.4 0.0247
     Manic/Hyperactive Behavior 34.1 0.0012 53.4 0.0002
     Depressed Mood 43.8 0.0831 62.5 0.0372

Aberrant Behavior Checklist – Community: FXS Specific (ABC-CFXS)

Scale: ABC-CFXS Group Mean Percent Improvement from Baseline
Week 12

(n=12)

P-value vs Baseline Week 38

(n=9)

P-value vs Baseline
Stereotypy 60.8 0.0048 73.2 0.0019
Social Avoidance 57.9 0.0040 75.4 0.0013
Socially Unresponsive/Lethargic 65.7 0.0024 83.3 0.0016
Inappropriate Speech 56.5 0.0002 66.1 <0.0001
Irritability 51.1 0.0012 63.7 0.0003
Hyperactivity 36.7 0.0119 48.2 0.0012

Safety Summary
ZYN002 was well tolerated, and the safety profile was consistent with previously reported clinical data, with no serious adverse events (SAEs) reported. Forty-three treatment-emergent adverse events (TEAEs) have been reported through week 38, all of which were mild or moderate. Most were unrelated to treatment with ZYN002. The most common TEAEs were gastroenteritis (14%) and upper respiratory tract infections (12%); all were considered unrelated and resolved during the study period. One patient, who has continued in the trial, developed moderate application rash, which resolved. No THC was detected in the plasma. No clinically meaningful trends in vital signs, ECG, or clinical safety laboratories including liver function tests (LFTs) were observed.

The Company plans to seek publication of these data and will provide future updates on the ongoing FAB-C study.

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. It is caused by a mutation in the Fragile X Mental Retardation gene (FMR1) located on the X chromosome and leads to dysregulation of the endocannabinoid pathway including the reduction in endogenous cannabinoids (2-AG and anandamide). 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 patients suffering with FXS.

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 and refractory epilepsies. 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.

Investor Contact
Will Roberts, VP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

Zynerba Pharmaceuticals Initiates CONNECT-FX, a Pivotal Clinical Trial of ZYN002 in Fragile X Syndrome

Study will Evaluate the Efficacy and Safety of Transdermally-Delivered Cannabidiol (CBD) in Children and Adolescents with Fragile X Syndrome

Top Line Results Expected in Second Half of 2019

Zynerba to host conference call and webcast today at 8:30 am

Devon, PA, July 9, 2018  —  Zynerba Pharmaceuticals, Inc.(NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced the initiation of a multi-national, randomized, double blind placebo controlled Clinical study of Cannabidiol (CBD) in Children and Adolescents with Fragile X (CONNECT-FX). The CONNECT-FX trial will evaluate the efficacy and safety of ZYN002 (CBD Gel) in children ages three to 17 with full mutation Fragile X syndrome (FXS). FXS is a genetic condition that causes intellectual disability, behavioral and learning challenges and is the most common known single gene cause of autism spectrum disorder. Top line results are expected in the second half of 2019.

“We are excited to initiate CONNECT-FX, the first-of-its-kind clinical study evaluating transdermally-delivered ZYN002 as a treatment for the debilitating behaviors associated with Fragile X syndrome,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We look forward to demonstrating the clinical effects of ZYN002 in treating some of the most common behavioral symptoms of Fragile X syndrome. If successful, ZYN002 has the potential to become the first product indicated for the treatment of behavioral symptoms of Fragile X syndrome and help address the ongoing needs of the children and families impacted by this syndrome.”

The CONNECT-FX study is a multi-national randomized, double-blind, placebo-controlled, 14-week study that will assess the efficacy and safety of ZYN002 for the treatment of children and adolescents with FXS. Approximately 200 male and female patients with Fragile X syndrome, confirmed with the full mutation of the FMR1 gene, will be enrolled at approximately 20 clinical sites in the United States, Australia, and New Zealand. Patients will be randomized 1:1 to either trial drug or placebo. Randomization will be stratified by gender, weight, and investigator geographic region. The primary endpoint is the change from baseline to the end of the treatment period in the Aberrant Behavior Checklist-Community FXS Specific (ABC-CFXS) Social Avoidance subscale. Key secondary endpoints are the change from baseline to the end of the treatment period in the ABC-CFXS Irritability subscale score, the ABC-CFXS Socially Unresponsive/Lethargic subscale score, and improvement in Clinical Global Impression – Improvement (CGI-I) at the end of the treatment period. Based on discussions with the U.S. Food and Drug Administration (FDA), the Company will anchor the CGI-I scale to behavioral symptoms of FXS. Consistent with recent guidance from the FDA on capturing the voice of the patient in drug development, additional qualitative data on the clinical relevance of various FXS behaviors to caregivers and patients will be collected. With positive results from this trial, Zynerba will request a meeting with the FDA to determine the acceptability of these data as the basis for an NDA filing.

“Children with Fragile X syndrome are dramatically impacted by this genetic condition and its debilitating behavioral and emotional challenges, including anxiety, social withdrawal, irritability, inattention and aggression,” said Elizabeth M. Berry-Kravis, M.D., Ph.D., Professor of Pediatrics, Neurological Sciences and Biochemistry at Rush University Medical Center. “In patients with Fragile X, augmentation of endogenous cannabinoid availability has the potential to positively impact social avoidance behaviors and anxiety during social interactions. I am excited to participate in a double-blind placebo-controlled study of cannabidiol in Fragile X. I hope to be part of the effort to move what may be the first product indicated specifically for Fragile X syndrome toward availability for my patients.”

Conference call information
Zynerba management will host a live conference call and webcast today at 8:30 am Eastern Time to discuss the initiation of CONNECT-FX. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 7163869. 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 Fragile X syndrome
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. It is caused by a mutation in the Fragile X Mental Retardation gene (FMR1) located on the X chromosome and leads to dysregulation of the endocannabinoid pathway including the reduction in endogenous cannabinoids (2-AG and anandamide). 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 patients suffering with FXS.

About Our Technology 
Cannabinoids are a class of chemical compounds that occur naturally in the human body and in the Cannabis plant and interact with numerous signaling systems and receptors in the central nervous system, giving them wide potential therapeutic application. The two primary cannabinoids contained in Cannabis are cannabidiol, or CBD, and ∆9-tetrahydrocannabinol, or THC. Clinical and preclinical data support the potential for CBD in treating epilepsy and Fragile X syndrome. Zynerba is developing therapeutic medicines that utilize innovative transdermal technologies that, if successful, may allow for sustained and controlled delivery of therapeutic levels of CBD. Transdermal delivery of cannabinoids may have benefits over oral dosing because it allows the drug to be absorbed through the skin directly into the bloodstream. This avoids first-pass liver metabolism, potentially enabling lower dosage levels of active pharmaceutical ingredients with a higher bioavailability and improved safety profile. Transdermal delivery also avoids the gastrointestinal tract, lessening the opportunity for GI related adverse events and the potential degradation of CBD by gastric acid into THC, which may be associated with unwanted psychoactive effects. Using an established pharmaceutical process for manufacturing, Zynerba replicates the CBD found in the Cannabis plant. We believe that this will allow us to meet stringent global regulatory agencies’ standards while ensuring that we can efficiently supply the amount of product required to meet the demand of the markets that we are targeting.

About ZYN002
Zynerba’s ZYN002 CBD gel is the first and only pharmaceutically-produced CBD formulated as a patent-protected permeation-enhanced transdermal gel and is being studied in children and adolescents with Fragile X syndrome and developmental and epileptic encephalopathies, and in adult epilepsy patients with focal seizures. ZYN002 is a clear, permeation-enhanced gel that is designed to provide controlled drug delivery transdermally with once- or twice-daily dosing.

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 and refractory epilepsies. 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.

Investor Contacts
Will Roberts, VP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

Zynerba Pharmaceuticals Announces Top Line Results from ZYN001 THC-Prodrug Patch Phase 1 Study

Devon, PA, July 5, 2018 — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, announced top line results from a Phase 1 clinical program studying ZYN001, the Company’s patent-protected, pro-drug of tetrahydrocannabinol (THC) delivered via a transdermal patch, in healthy volunteers. The program assessed the safety and pharmacokinetics in single and multiple doses of several formulations of ZYN001.

The top line results of this Phase 1 study indicate that target blood levels of 5 to 15 ng/ml THC were not achieved. ZYN001 was very well tolerated with minimal skin erythema. There were no serious adverse events or discontinuations for subjects receiving ZYN001.

As a result of these data, the Company will focus its development efforts and investments on the ZYN002 Fragile X syndrome, developmental and epileptic encephalopathy (DEE) and adult refractory epilepsy programs. The Company expects that this change will extend its cash runway into the second half of 2019.

This Phase 1 study was a single and multiple dose, placebo-controlled first-in-man study to assess the safety and pharmacokinetics of ZYN001 administered as a transdermal patch to healthy adult subjects. Several formulations and patch wear times ranging from 24 hours to 14 days were assessed in in 60 healthy subjects who were randomized to ZYN001 or placebo.

Financial Outlook 
The Company now believes that the cash and cash equivalent position of $52.1 million as of March 31, 2018 is sufficient to fund operations and capital requirements into the second half of 2019.

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 and refractory epilepsies. 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.

Investor Contact
Will Roberts, VP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com