Month: November 2022

Devon, PA, November 29, 2022  — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced the presentation of a poster at the 61^st Annual Meeting of the American College of Neuropsychopharmacology, being held December 4-7, 2022 in Phoenix, Ariz. A copy of the poster will be made available on the Zynerba corporate website following the presentation at www.zynerba.com/publications.

Poster Presentation Details
Title:	An Open-Label Tolerability and Efficacy Study of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE)
Date available:	Available online beginning December 5, 2022 for entirety of conference
Live presentation:	In-person presentation, Poster Session III, December 7, 2022, 5:30 p.m. – 7:30 p.m. MST
Location:	JW Marriott Desert Ridge Resort and Spa, Phoenix, Ariz.

About Zygel
Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS), 22q11.2 deletion syndrome (22q) and autism spectrum disorder (ASD). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome, 22q11.2 deletion syndrome and autism spectrum disorder. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation or global instability, including political instability, may disrupt our business operations or our financial condition. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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

Study finds patients with Fragile X who have a highly methylated FMR1 gene that were treated with Zygel showed a significant reduction in behavioral symptoms compared to those treated with placebo

Topline results from follow-on RECONNECT confirmatory pivotal Phase 3 trial of Zygel in patients with a completely methylated FMR1 gene expected in second half 2023

Devon, PA, November 28, 2022 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that the results from the Phase 3 CONNECT-FX study of Zygel for the treatment of behavioral symptoms in children and adolescents with Fragile X syndrome (FXS) were published in the Journal of Neurodevelopmental Disorders.

The paper titled, “A Randomized, Controlled Trial of ZYN002 Cannabidiol Transdermal Gel in Children and Adolescents with Fragile X Syndrome (CONNECT-FX),” details how Zygel was well tolerated in patients with FXS and demonstrated efficacy with a favorable benefit risk profile in patients with ≥90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe. The article can be accessed online at the Journal of Neurodevelopmental Disorders at https://rdcu.be/c0sKz.

“Children with Fragile X syndrome are dramatically impacted by debilitating behavioral and emotional challenges, including anxiety, social avoidance, irritability, inattention and aggression,” said Elizabeth Berry-Kravis, M.D., Ph.D., Professor, Department of Pediatrics and Neurological Sciences, Rush University Medical Center. “The results from CONNECT-FX offer hope for children with FXS and their caregivers as additional treatment options are needed for children who continue to struggle with this condition.”

CONNECT-FX was a randomized, double-blind, multinational, 14-week study to evaluate the efficacy and safety of Zygel in children and adolescents aged 3 to 17 years. A total of 212 patients were randomized to 12 weeks of Zygel (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The trial was conducted at 21 investigational centers in the U.S., Australia and New Zealand. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist–Community Edition FXS (ABC-C_FXS) SA subscale in the full cohort of patients with full mutation FXS, regardless of the FMR1 gene methylation status. Ad hoc analyses assessed efficacy in patients with ≥90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely.

Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥90% methylation of FMR1 (nominal p=0.020), representing 80% of the overall study population. This group also achieved statistically significant improvements in Caregiver Global Impression-Change in SA and Isolation, Irritable and Disruptive Behaviors, and Social Interactions (nominal p-values: p=0.038, p=0.028, and p=0.002, respectively). Similar results were seen in patients with 100% methylation of FMR1, representing 65% of the study population. Zygel was generally well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (Zygel: 6.4%; placebo: 1.0%).

“CONNECT-FX provided evidence that a biologically identifiable and clinically responsive population of patients with FXS, who are defined by both full mutation and greater than or equal to 90% methylation of the FMR1 gene, benefited from treatment with Zygel,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “Given these findings, our follow-on pivotal Phase 3 trial, RECONNECT, is underway to confirm the results observed in this population. We believe having patients with complete methylation of their FMR1 gene as the primary analysis population improves our chance of success and we look forward to topline results from RECONNECT in the second half of 2023 and believe the results, if positive, will be sufficient to support the submission of a New Drug Application in the U.S. and Marketing Authorization Application in the EU for Zygel in patients with FXS.”

About Zygel
Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e., through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS), 22q11.2 deletion syndrome (22q) and autism spectrum disorder (ASD). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About Fragile X Syndrome (FXS)
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 4,000 males and 1 in 6,000 females. It is the most common inherited intellectual disability in males and a significant cause of intellectual disability in females, and the leading genetic cause of autism spectrum disorder (ASD). The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. In the U.S., there are about 78,000 people suffering with FXS, approximately 60% of whom have complete methylation of the FMR1 gene.

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

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome, 22q11.2 deletion syndrome and autism spectrum disorder. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation or global instability, including political instability, may disrupt our business operations or our financial condition. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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

Media Contact
Laura Morgan
Sam Brown Inc.
Cell: 951.333.9110
lauramorgan@sambrown.com

Devon, PA, November 15, 2022 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that the European Commission (EC) has granted orphan drug designation to cannabidiol, the active ingredient in its transdermal gel, Zygel™, for the treatment of 22q11.2 deletion syndrome (22q).

“We are pleased to have been granted orphan drug designation in the U.S. and now the EU, which we believe reflects the unmet medical need for new therapies to treat 22q,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “Orphan drug designation is another important step forward in advancing Zygel as a potential new treatment option for patients with 22q.”

Orphan drug designation is granted to medicines that treat, prevent or diagnose a life-threatening or chronically debilitating rare disease, with a prevalence in the European Union (EU) of not more than 5 in 10,000, and with either no currently approved method of diagnosis, prevention or treatment or with significant benefit to those affected by the disease. The designation provides certain benefits to Zynerba, including 10-year EU market exclusivity upon regulatory approval, if received, reductions in European Medicines Agency application fees, and access to protocol assistance.

The Company believes there are approximately 112,000 patients with 22q in the EU and approximately 129,000 in Europe including the United Kingdom.

Zygel was previously granted orphan drug designation by the EC for the treatment of Fragile X syndrome (FXS) and by U.S. Food and Drug Administration (FDA) for the treatment of FXS and 22q. Additionally, the FDA has granted Fast Track designation for Zygel for the treatment of behavioral symptoms associated with FXS.

In June 2022, the Company announced positive topline results from the exploratory, open label Phase 2 INSPIRE trial of Zygel in children and adolescents with 22q (Press Release). Based on the positive Phase 2 data, the Company requested and has been granted an initial meeting with the FDA before the end of 2022 to obtain feedback on the Phase 2 data and regulatory pathway for Zygel in patients with 22q.

About Zygel
Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS), 22q11.2 deletion syndrome (22q) and autism spectrum disorder (ASD). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About 22q11.2 Deletion Syndrome (22q)
As the second most common chromosomal disorder after Down syndrome, 22q is caused by a small missing piece of the 22nd chromosome. The deletion occurs near the middle of the chromosome at a location designated q11.2. It is considered a mid-line condition, with physical symptoms including characteristic palate abnormalities, heart defects, immune dysfunction, and esophageal / GI issues, as well as debilitating neuropsychiatric and behavioral challenges. Anxiety is among the most common neuropsychiatric symptoms of 22q and researchers have found that for children with 22q, anxiety is linked to poorer adaptive behaviors such as self-care and communication skills that affect daily life. Children with 22q also experience withdrawn behavior, ADHD, cognitive impairment, and autism spectrum disorder that affect communication and social interaction. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia. It is estimated that 22q occurs in between one in 3,000 and one in 6,000 live births, suggesting that there are approximately 83,000 people living with 22q in the U.S. In addition, Zynerba believes that there are approximately 112,000 patients with 22q in the EU and approximately 129,000 in Europe if the United Kingdom is included.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome, 22q11.2 deletion syndrome and autism spectrum disorder. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation or global instability, including political instability, may disrupt our business operations or our financial condition. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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

Enrollment continues in RECONNECT, a confirmatory pivotal Phase 3 trial of Zygel™ in patients with Fragile X syndrome (FXS); topline results expected second-half 2023

$55.9 million in cash and cash equivalents at September 30, 2022; Cash runway into first quarter 2024

Devon, PA, Novemer 14, 2022  — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today reported financial results for the third quarter ended September 30, 2022, and provided an overview of recent operational highlights and a pipeline update.

“Enrollment in our confirmatory pivotal Phase 3 RECONNECT trial continues, and we expect topline results in the second half of 2023,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “With a cash runway into the first quarter of 2024, we remain well-positioned on achieving our goal of bringing Zygel to market as the first FDA approved treatment option for the significant unmet medical need that affects FXS patients and their families.”

Operational Highlights and Pipeline Update

Zygel in Fragile X Syndrome (FXS)

• The Company continues to expect topline results from RECONNECT, a confirmatory pivotal Phase 3 trial of Zygel in patients with FXS, in the second half of 2023. The Company believes that the results from RECONNECT, if positive, will be sufficient to support the submission of a New Drug Application (NDA) for Zygel in patients with FXS.
• In October 2022 the Company announced that the U.S. Patent and Trademark Office (USPTO) issued a patent titled “Treatment of Fragile X Syndrome With Cannabidiol,” which includes claims directed to methods of treating Fragile X syndrome with cannabidiol. This new patent, which expires in 2038, is part of an expanding international intellectual property portfolio covering the Company’s transdermal cannabidiol product candidate, Zygel. (Press Release)

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

• Based on the positive Phase 2 INSPIRE trial data announced in June 2022 (Press Release), the Company requested and has been granted an initial meeting with the U.S. Food and Drug Administration (FDA) before the end of 2022 to obtain feedback on the Phase 2 data and regulatory pathway for Zygel in patients with 22q. The Company currently plans to initiate a Phase 3 program in children and adolescents with 22q following topline results from RECONNECT.
• In November 2022, the Company announced that the USPTO issued a patent titled “Treatment of 22q11.2 Deletion Syndrome With Cannabidiol,” which includes claims directed to methods of treating one or more behavioral symptoms of 22q with cannabidiol, and expires in 2040. (Press Release)
• The Company presented data at The Society for the Study of Behavioural Phenotypes (SSBP) 24^th International Research Symposium in September 2022 and the 2022 National Organization for Rare Disorders (NORD) Rare Diseases and Orphan Products Breakthrough Summit in October 2022 from the first 14-week treatment period of the Phase 2 INSPIRE trial. These data suggest a positive risk-benefit profile for Zygel in improving anxiety-related and behavioral symptoms in children and adolescents with 22q. Statistically significant improvements from baseline were seen in the Pediatric Anxiety Rating Scale (PARS-R), the total score and all five subscales of the Anxiety, Depression and Mood Scale (ADAMS) and all five subscales of the Aberrant Behavior Checklist – Community (ABC-C). In addition, the majority of patients showed clinically meaningful improvements as demonstrated by the Clinical Global Impression – Improvement (CGI-I). Zygel was shown to be well tolerated, and the safety profile was consistent with previously released data from other Zygel clinical trials. (Posters).

Third Quarter 2022 Financial Results

Research and development expenses were $5.0 million for the third quarter of 2022, including stock-based compensation of $0.5 million. General and administrative expenses were $3.5 million in the third quarter of 2022, including stock-based compensation expense of $0.6 million. Net loss for the third quarter of 2022 was $8.7 million, with basic and diluted loss per share of $(0.20).

Financial Outlook

As of September 30, 2022, cash and cash equivalents were $55.9 million, compared to $67.8 million as of December 31, 2021.

On May 11, 2021, the Company entered into a Controlled Equity Offering^SM Sales Agreement (2021 Sales Agreement), with Cantor Fitzgerald & Co., Canaccord Genuity, LLC, H.C. Wainwright & Co. LLC and Ladenburg Thalmann & Co. Inc., as sales agents, pursuant to which the Company may sell, from time to time, up to $75.0 million of its common stock. In the third quarter of 2022, the Company sold and issued 2,579,346 shares of its common stock under the 2021 Sales Agreement in the open market resulting in gross proceeds of $3.2 million and net proceeds of $3.0 million, after deducting commissions and offering expenses.

On July 21, 2022, the Company entered into a Purchase Agreement and registration rights agreement for up to $20 million with Lincoln Park Capital Fund, LLC (LPC), a Chicago-based institutional investor. In the third quarter of 2022, the Company sold and issued 200,000 shares of its common stock under the 2022 Purchase Agreement with LPC in the open market resulting in gross proceeds of $0.2 million and net proceeds of $0.1 million, after deducting offering expenses.

Management believes that the Company’s cash and cash equivalents are sufficient to fund operations and capital requirements into the first quarter of 2024. Top-line results from the Company’s confirmatory pivotal Phase 3 RECONNECT trial of Zygel in patients with FXS are expected in the second half of 2023.

About Zygel

Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS), 22q11.2 deletion syndrome (22q) and autism spectrum disorder (ASD). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and from the FDA for the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About Zynerba Pharmaceuticals, Inc.

Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome, 22q11.2 deletion syndrome and autism spectrum disorder. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration and foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation or global instability, including political instability, may disrupt our business operations or our financial condition. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

ZYNERBA PHARMACEUTICALS, INC.

CONSOLIDATED STATEMENTS OF OPERATIONS

		(unaudited)
		Three months ended September 30,								Nine months ended September 30,
			2022				2021				2022				2021
Operating expenses:
Research and development		$	5,039,228			$	6,341,171			$	15,632,150			$	16,402,129
General and administrative			3,453,648				3,869,481				10,933,411				11,531,824
Total operating expenses			8,492,876				10,210,652				26,565,561				27,933,953
Loss from operations			(8,492,876	)			(10,210,652	)			(26,565,561	)			(27,933,953	)
Other income (expense):
Interest income			251,855				5,038				439,590				16,614
Foreign exchange loss			(435,128	)			(376,637	)			(893,803	)			(576,619	)
Total other income (expense)			(183,273	)			(371,599	)			(454,213	)			(560,005	)
Net loss		$	(8,676,149	)		$	(10,582,251	)		$	(27,019,774	)		$	(28,493,958	)
Net loss per share – basic and diluted		$	(0.20	)		$	(0.26	)		$	(0.65	)		$	(0.73	)
Basic and diluted weighted average shares outstanding			43,746,878				40,092,128				41,831,998				38,933,209
Non-cash stock-based compensation included above:
Research and development		$	482,306			$	818,390			$	1,500,447			$	2,443,667
General and administrative			558,794				751,603				1,809,678				2,325,512
Total		$	1,041,100			$	1,569,993			$	3,310,125			$	4,769,179

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED BALANCE SHEETS

		(unaudited)
		September 30, 2022				December 31, 2021
Assets
Current assets:
Cash and cash equivalents		$	55,934,491			$	67,808,000
Incentive and tax receivables			1,378,738				9,580,468
Prepaid expenses and other current assets			3,487,626				2,831,392
Total current assets			60,800,855				80,219,860
Property and equipment, net			419,863				385,833
Incentive and tax receivables			751,815				—
Right-of-use assets			394,205				565,814
Total assets		$	62,366,738			$	81,171,507
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable		$	1,619,697			$	1,798,813
Accrued expenses			7,598,187				7,896,598
Lease liabilities			213,428				209,068
Total current liabilities			9,431,312				9,904,479
Lease liabilities, long-term			178,672				353,694
Total liabilities			9,609,984				10,258,173
Stockholders’ equity:
Common stock			47,063				41,218
Additional paid-in capital			319,210,944				310,353,595
Accumulated deficit			(266,501,253	)			(239,481,479	)
Total stockholders’ equity			52,756,754				70,913,334
Total liabilities and stockholders’ equity		$	62,366,738			$	81,171,507

Zynerba Contacts

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

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

Devon, PA, November 2, 2022  — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that the U.S. Patent and Trademark Office has issued Patent No. 11,458,109, titled “Treatment of 22q11.2 Deletion Syndrome With Cannabidiol,” which includes claims directed to methods of treating one or more behavioral symptoms of 22q11.2 deletion syndrome with cannabidiol.

This new patent, which expires in 2040, is part of an expanding international intellectual property portfolio covering the Company’s transdermal cannabidiol product candidate, Zygel. There are currently seven corresponding U.S. patents and one corresponding EU patent related to methods of treating Fragile X syndrome, 22q11.2 deletion syndrome or autism spectrum disorder.

About Zygel
Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS), 22q11.2 deletion syndrome (22q) and autism spectrum disorder (ASD). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and by the FDA for the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About 22q11.2 Deletion Syndrome (22q)
As the second most common chromosomal disorder after Down syndrome, 22q is caused by a small missing piece of the 22nd chromosome. The deletion occurs near the middle of the chromosome at a location designated q11.2. It is considered a mid-line condition, with physical symptoms including characteristic palate abnormalities, heart defects, immune dysfunction, and esophageal / GI issues, as well as debilitating neuropsychiatric and behavioral challenges. Anxiety is among the most common neuropsychiatric symptoms of 22q and researchers have found that for children with 22q, anxiety is linked to poorer adaptive behaviors such as self-care and communication skills that affect daily life. Children with 22q also experience withdrawn behavior, ADHD, cognitive impairment, and autism spectrum disorder that affect communication and social interaction. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia. It is estimated that 22q occurs in between one in 3,000 and one in 6,000 live births, suggesting that there are approximately 83,000 people living with 22q in the U.S. In addition, Zynerba believes that there are approximately 112,000 patients with 22q in the EU and approximately 129,000 in Europe if the United Kingdom is included.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome, 22q11.2 deletion syndrome and autism spectrum disorder. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation or global instability, including political instability, may disrupt our business operations or our financial condition. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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