Zynerba Pharmaceuticals Reports Fourth Quarter and Year End 2019 Financial Results and Operational Highlights

– Key Recent Clinical Milestones Include Completion of Enrollment in Pivotal CONNECT-FX Trial in Fragile X Syndrome and Phase 2 BRIGHT Trial in Autism Spectrum Disorder –

Devon, PA, March 10, 2020  — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today reported financial results for the fourth quarter and full year ended December 31, 2019 and provided an overview of recent operational highlights.

“The fourth quarter of 2019 capped off a year of strong execution by Zynerba,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “With a number of shots-on-goal in our clinical pipeline, each with near term milestones, our outlook is promising for the remainder of 2020 and beyond. We are positioned for major news events throughout this year and next, including the topline results from our pivotal CONNECT-FX trial of Zygel™ in patients with Fragile X syndrome which are expected late next quarter.”

Fourth Quarter 2019 and Recent Highlights

Zygel in Fragile X Syndrome (FXS)

Enrollment Complete in Pivotal FXS Trial; Topline Results Expected in the Second Quarter of 2020

Enrollment is complete with 212 patients randomized into 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. 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 and the ABC-CFXS Socially Unresponsive/Lethargic subscale score, and Clinical Global Impression – Improvement (CGI-I) at the end of the treatment period. The Company expects to report topline results late in the second quarter of 2020. If the results are positive, Zynerba intends to request a meeting with the FDA to determine the acceptability of the data as a basis for a New Drug Application (NDA) and to seek advice on preparation of the marketing authorization. The Company expects to submit its 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. (Press release)

Robust Enrollment Continues into Open Label Extension Study

During the screening phase of CONNECT-FX, caregivers of patients in the trial were informed that their participating child may have the opportunity to receive Zygel in an open label extension trial following the child’s compliant completion of CONNECT-FX, regardless of their child’s perceived response or actual blinded drug assignment at randomization in CONNECT-FX. As of March 9, 2020, 97% of the 163 patients who have completed the 14-week blinded portion of the CONNECT-FX trial have enrolled in the open label extension trial.

New U.S. Patent Received for Treatment of FXS with Transdermal Cannabidiol (CBD)

The U.S. Patent and Trademark Office issued U.S. 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 CBD daily via a gel or cream. This new patent expires in 2038 and is part of an expanding intellectual property portfolio covering Zygel. (Press release)

Poster Describing Health State Utility Indices (HUI) that Estimate the Severity of FXS and Other Pediatric Disorders  Presented at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting

An HUI specific to FXS, known as the ABC-UI, was derived from the ABC-CFXS to measure the health-related quality of life (HRQoL) benefit of treatments for FXS (Kerr C et al. Qual Life Res.2015;24(2):305-314); HUI are measured on a scale of 0 to 1 and used in clinical and economic analyses of therapies with potential impact on HRQoL. This poster described the evaluation of the potential benefit of Zygel on the ABC-UI in FXS through post hoc analysis of data from the FAB-C trial. The mean ABC-UI for FXS patients was calculated to be 0.57 at baseline, estimating a significant disease-related impact on HRQoL in FXS despite the children and adolescents in the study being maintained on standard of care for FXS, and suggesting an impact similar or worse than other debilitating pediatric conditions as described in the published literature in measures of HUI. Additionally, compared to baseline, patients receiving Zygel experienced significant (P < 0.01) and sustained improvement in their mean ABC-UI from week 4 to 12. (Press release)

Poster Describing Caregivers’ Perspectives on FXS Diagnosis and Patient Journey Perspective Presented at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting

The poster described the results of a caregiver survey that found an average age of 3 years at initial diagnosis, a high prevalence of comorbid conditions including ASD and attention-deficit/hyperactivity disorder, and standard of care consisting primarily of counseling/therapy and prescription medications that are not indicated for FXS. While caregivers of children with FXS often notice a variety of initial symptoms early and seek help from a health care professional, it is not until subsequent physician visits, often involving a specialist, that a formal diagnosis is made. (Press release)

Zygel in Autism Spectrum Disorder (ASD)

Completed Enrollment in Phase 2 Open Label Trial of Zygel in ASD; Topline Results Expected in the Second Quarter of 2020

Enrollment is complete in the Phase 2 BRIGHT trial assessing the safety, tolerability and efficacy of Zygel for the treatment of pediatric and adolescent patients with ASD. The 14-week trial is evaluating the efficacy and safety of Zygel in 37 children and adolescents (ages four through 17) with moderate-to-severe 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. The mean age of the 37 patients enrolled in the BRIGHT trial is 9.2 years. Ninety-two (92) percent of the enrolled patients are male, accurately reflecting the overall prevalence and gender ratio of moderate-to-severe ASD in the United States and in other studies. Zynerba expects to report topline results from this study in the second quarter of 2020. (Press release)

New U.S. Patent Received for Treatment of ASD with Transdermal Cannabidiol

The U.S. Patent and Trademark Office has issued U.S. Patent No. 10,568,848, titled “Treatment of Autism with Cannabidiol” which includes claims directed to methods of treating ASD by transdermally administering, via a gel or cream, a therapeutically effective amount of purified CBD. The patent expires in 2038. (Press release)

Poster Describing the Baseline Characteristics of Patients in Phase 2 BRIGHT Trial in ASD Presented at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting

The poster further describes the baseline characteristics of the pediatric and adolescent patients in the fully-enrolled Phase 2 BRIGHT trial, indicating that the trial enrolled a broad patient population and was enriched for disease severity to avoid floor effects on outcome measures. At baseline, at least 92% of patients have moderate to severe symptoms of ASD as measured by the Autism Diagnostic Observation Schedule (ADOS®-2) comparison score and the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) severity level score; this severity is further confirmed by an ABC-C Irritability subscale score of 30. In addition, 24% of patients enrolled in the BRIGHT trial had a PRAS-ASD score of >52, indicating possible clinical anxiety. (Press release)

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

Phase 2 Open Label Trial of Zygel in 22q Ongoing; Data Now Expected in the Third Quarter 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 now expects to report topline results from this study in the third quarter of 2020.

Zygel in Developmental and Epileptic Encephalopathies (DEE)

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

Zynerba expects to meet with the FDA to discuss the clinical path forward in DEE. Based on the Phase 2 trial design and positive efficacy and safety results, Zynerba anticipates that it will discuss the pursuit of an indication that includes all syndromes and encephalopathies in the DEE category that present with focal impaired-awareness seizures (FIAS; previously known as complex partial seizures) and/or convulsive seizures (CS), the most common and debilitating seizure types representing 75% to 80% of all seizures.

Corporate

Enhanced Senior Management Team

Paul M. Kirsch joined Zynerba as Vice President of Regulatory Affairs and Quality Assurance, bringing 30 years of regulatory affairs management experience with companies including Trevena, Inc., Iroko Pharmaceuticals, LLC, Teva Pharmaceuticals, and Cephalon, Inc. He has extensive regulatory experience with orphan and neuroscience products, and has led five successful NDAs into commercialization in multiple indications.

Fourth quarter and full year 2019 Financial Results

As of December 31, 2019, cash and cash equivalents were $70.1 million, compared to $59.8 million as of December 31, 2018. Research and development expenses for the fourth quarter of 2019 were $7.5 million, including stock-based compensation of $0.5 million. General and administrative expenses for the fourth quarter of 2019 were $4.0 million, including stock-based compensation expense of $0.8 million. The net loss for the fourth quarter of 2019 was $10.7 million with basic and diluted net loss per share of $(0.46).

Research and development expenses for the year ended December 31, 2019 were $20.4 million, including stock-based compensation of $2.4 million. General and administrative expenses for the year ended December 31, 2019 were $13.9 million, including stock-based compensation expense of $3.2 million. The net loss for the full year of 2019 was $32.9 million with basic and diluted net loss per share of $(1.50).

Financial Outlook

The Company’s cash and cash equivalents as of December 31, 2019 was $70.1 million. Management believes that the cash runway 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; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; and the timing and outcome of current and future legal proceedings. 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.

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

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

Zynerba Pharmaceuticals Announces Poster Presentations at the American Academy of Neurology (AAN) 2020 Annual Meeting

Devon, PA, March 9, 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 acceptance and presentation details of three posters at the American Academy of Neurology (AAN) 2020 Annual Meeting. The meeting is being held in Toronto, Canada from April 25th through May 1, 2020.

“These new data at AAN provide additional information on the safety and observed experimental profile of activity of Zygel™ in the exploratory Phase 2 FAB-C trial in Fragile X syndrome and the Phase 2 BELIEVE 1 trial in developmental and epileptic encephalopathies, and the potential of Zygel to improve patient quality of life,” said Joseph Palumbo, MD, FAPA, MACPsych, Chief Medical Officer of Zynerba. “On behalf of the families and investigators participating in the Zygel clinical development program, we are excited to share these study findings and key learnings with the larger scientific community attending AAN this year.”

Wednesday, April 29 from 8:00 AM to 9:00 AM.

Poster Title: “Cannabidiol Transdermal Gel in Children and Adolescents with Developmental and Epileptic Encephalopathies: An Open-label Clinical Trial”
Abstract number: 1631
Poster session: P11
Poster grouping: Epilepsy/Clinical Neurophysiology (EEG): Antiepileptic Medications/Neurostimulation and Diet Therapies 1 (in Poster Neighborhood #4)
Presentation number: 007

Poster Title: “Quality of Life and Qualitative Caregiver Assessments in Children and Adolescents with Developmental and Epileptic Encephalopathies Treated with Cannabidiol Transdermal Gel: An Open-label Clinical Trial”
Abstract number: 1664
Poster session: P11
Poster grouping: Epilepsy/Clinical Neurophysiology (EEG): Antiepileptic Medications/Neurostimulation and Diet Therapies 1 (in Poster Neighborhood #4)
Presentation number: 006

Thursday, April 30 from 12:00 PM to 1:00 PM.

Poster Title: “Cannabidiol Transdermal Gel for the Treatment of Fragile X Syndrome: Post hoc Responder Analysis and Pattern of Efficacy on domains of the Aberrant Behavior Checklist-FXS (ABC-CFXS)”
Abstract number: 4743
Poster session: P15
Poster grouping: Child Neurology and Developmental Neurology: Neurogenetics 3 (in Poster Neighborhood #11)
Presentation number: 002

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.

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

Zynerba Pharmaceuticals to Present at the 32nd Annual ROTH Conference

Devon, PA, March 5, 2020 — 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 32nd Annual ROTH Conference. The presentation will take place on Monday, March 16, 2020 at 3:30PM PT at the Ritz-Carlton, Laguna Niguel. 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

Zynerba Pharmaceuticals Presents Data Showing that the Baseline Characteristics of Patients in Phase 2 BRIGHT Trial in Autism Spectrum Disorder Indicate a Moderate-to-Severe Study Population

– New Data Presented Today at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting –

Devon, PA, March 3, 2020 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, is presenting data this week further describing the baseline characteristics of the pediatric and adolescent patients in the fully-enrolled Phase 2 BRIGHT trial of Zygel™ (CBD transdermal gel; ZYN002) in children and adolescents with autism spectrum disorder (ASD), indicating that the trial enrolled a broad population of patients with moderate-to-severe ASD.

The poster entitled Phase 2 BRIGHT (An Exploratory Open-Label Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Autism Spectrum Disorder) Trial: Baseline Characteristics (poster #27) is being presented at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting. The poster is being presented on Tuesday, March 3 from 5:00 to 6:00 PM EST and Wednesday, March 4 from 5:00 to 7:00 PM EST. These data will also be presented during the ASENT Pipeline Data Blitz session on Wednesday March 4, 2020 from 1:00 to 3:00PM EST. The meeting is being held in Bethesda, MD on March 2nd through March 5th, 2020. A copy of the poster is available on the Zynerba corporate website at http://zynerba.com/publications/.

Zynerba’s Chief Medical Officer, Joseph M. Palumbo, MD, FAPA, MACPsych, is presenting data describing the baseline characteristics of patients enrolled in the ongoing BRIGHT trial, which indicate a patient population with predominantly moderate-to-severe ASD as measured by key scales used for screening and efficacy assessment. These include the Aberrant Behavior Checklist – Community (ABC-C); the Autism Diagnostic Observation Schedule® (ADOS-2); and the Parent Rated Anxiety Scale–Autism Spectrum Disorder (PRAS-ASD).

“ASD is a complex neurodevelopmental disorder characterized by difficulties with behaviors, communication, and social interaction,” said Dr. Palumbo. “Pediatric and adolescent patients with ASD may also present with profound clinical anxiety, above the rate seen in neurotypical children, further complicating their condition and treatment regimen. Unfortunately, current ASD management options are restricted to cognitive behavioral therapy and a small number of approved pharmacologic treatments, highlighting the substantial unmet need for novel therapies in this population. We believe that we have enrolled an appropriate population of patients into our well-designed exploratory BRIGHT trial to enable a robust analysis of outcomes to help inform the design of future double-blind, placebo-controlled studies.”

The endocannabinoid system – a key modulator of emotion and social behavior – is dysregulated in ASD, and published data suggest that cannabidiol (CBD) may provide therapeutic benefit. However, the efficacy and safety of CBD in patients with ASD have not been well established. Zynerba is undertaking the 14-week BRIGHT Phase 2 exploratory trial in children and adolescents (ages four through 17 years) with ASD as confirmed by Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria to assess the safety and efficacy of Zygel in treating ASD-related behaviors as measured by a variety of efficacy assessments which are shown in Figure 1, below. After completing dosing in the 14-week period, participants may enroll in a six-month extension trial.

Figure 1. Schedule of Screening and Efficacy Assessments

The trial protocol included certain inclusion and exclusion criteria to enrich the trial population for disease severity at baseline, as measured by the following assessments:

ABC-C

  • A 58-item caregiver-rated scale measuring behaviors across 5 subscales: irritability/agitation (maximum score: 45), lethargy/social withdrawal (maximum score: 48), stereotypic behavior (maximum score: 21), hyperactivity/noncompliance (maximum score: 48), inappropriate speech (maximum score: 12);
  • Each behavior is scored from 0 (“not at all a problem”) to 3 (“the problem is severe in degree”);
  • Higher scores indicate greater severity of aberrant behavior.

ADOS-2

  • A diagnostic tool consisting of 5 age – and verbal ability – dependent modules that assess social communication and core behaviors of ASD;
  • Each item is scored by a trained test administrator from 0 (“no abnormality of type specified”) to 3 (“moderate to severe abnormality”);
  • ADOS total scores are diagnostic; however, standardized comparison scores can be used to measure severity;
  • Comparison scores range from 0-10, with scores of <5 indicating mild ASD, scores of 5-7 indicating moderate ASD, and scores of 8-10 indicating severe ASD.

PRAS-ASD

  • A 25-item parent-rated scale assessing anxiety in ASD;
  • Each item is scored from 0 (“not present”) to 3 (“very frequent and a major problem”);
  • Maximum score is 75, with scores >52 indicating possible clinical anxiety.

Baseline Disease Characteristics

As seen in Table 1 below, the majority of patients had moderate or severe ASD at baseline as measured by the ADOS-2 comparison score (94%) and DSM-5 severity levels (92%). In addition, the mean ABC-C Irritability score was 30.0, and 24% of the enrolled patients had PRAS-ASD scores indicative of possible clinical anxiety, further highlighting the severity of symptoms in the enrolled patient population.

Table 1. Baseline Disease Characteristics of Patients Enrolled in BRIGHT

The authors conclude that the Phase 2 BRIGHT trial has successfully enrolled a broad patient population and was enriched for disease severity to avoid floor effects on outcome measures. The baseline characteristics indicate a patient population with predominantly moderate-to-severe ASD, with a high level of clinically significant anxiety.

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

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

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

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

[i] DSM-5 severity levels are based on degree of social communication impairment and behavioral flexibility. The levels indicate patients “requiring support” (level 1), “requiring substantial support” (level 2), and “requiring very substantial support” (level 3).

 

Zynerba Pharmaceuticals Presents Health State Utility Index Data on Severity of Fragile X Syndrome (FXS) and Diagnostic Challenges Faced by Caregivers

– Data Presented at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting –

– Health State Utility Index Data Estimate the Significant Health Burden of FXS, and Suggest the Potential Benefit of Treatment with Zygel™ –

– Caregiver’s Perspective on Protracted Journey to Diagnosis, Current Standard of Care and Comorbid Conditions Described –

Devon, PA, March 3, 2020 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, is presenting two posters this week on the health burden and diagnostic challenges of Fragile X syndrome (FXS). These data are being presented at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting, which is being held in Bethesda, MD on March 2nd through March 5th, 2020.

The first poster presents health state utility indices that estimate the severity of pediatric disorders including FXS, and the potential benefit of Zygel (CBD transdermal gel; ZYN002) in children and adolescents with FXS. Joseph M. Palumbo, MD, FAPA, MACPsych, Chief Medical Officer of Zynerba, will also present these data during the ASENT Pipeline Data Blitz on March 4. The second poster speaks to the initial family experience in FXS, expanding upon the existing knowledge of patient presentation, diagnosis and understanding of FXS; the protracted journey to diagnosis; and the high prevalence of comorbid conditions. A copy of the posters are available on the Zynerba corporate website at http://zynerba.com/publications/.

Post Hoc Analysis – An Open-Label Study of Transdermal Cannabidiol (ZYN002) for the Treatment of Fragile X Syndrome in Children and Adolescents: Estimating Health State Utility Scores

  • Poster number: 29
  • Poster presentation time: Tuesday, March 3 from 5:00 to 6:00 PM and Wednesday, March 4 from 5:00 to 7:00 PM.
  • Oral presentation time: Wednesday, March 4 from 1:00 to 3:00 PM during the ASENT Pipeline Data Blitz session.

FXS is a rare genetic condition characterized by a range of developmental, neuropsychiatric, and behavioral symptoms. The spectrum and severity of FXS symptoms result in a high clinical, humanistic, and economic burden on patients and caregivers, including important healthcare resource utilization and associated costs. Health state utility indices (HUI) are used in clinical and economic analyses of therapies with potential impact on health-related quality of life (HRQoL) and enable comparison of HRQoL across conditions. Health state utility is measured on a 0 to 1 scale in which 0 represents death and 1 represents complete health; the lower the score, the more significant the impact of the disease to HRQoL. The Aberrant Behavior Checklist – Community Utility Index (ABC-UI) – a utility index specific to FXS – was derived from the Aberrant Behavior Checklist – Community for FXS (ABC-CFXS) to measure the HRQoL benefit of treatments for FXS. The ABC-UI, created and subsequently published in the peer-reviewed journal Quality of Life Research, in 2015, established an algorithm that calculates utility index score based on ABC-CFXS items pertaining to the core symptom domains of FXS.

“The mean health state utility index score for FXS in this seminal analysis was calculated to be 0.57, estimating a significant disease-related impact on HRQoL in FXS which may be as robust as, or perhaps even more impactful, than that described in the published literature for other debilitating pediatric conditions in measures of HUI”, said Dr. Palumbo. “We will work to confirm our initial observations in future analyses.”

The objective of the analysis undertaken was to evaluate the potential benefit of Zygel on the ABC-UI in pediatric and adolescent patients with FXS through post hoc analysis of data from the Phase 2 open label FAB-C (Treatment of Fragile X Syndrome Anxiety and Behavioral Challenges with CBD) trial. Individual patient-level data from the FAB-C study were mapped to the ABC-UI algorithm to generate a utility index score for each patient.

“Fragile X syndrome is a debilitating diagnosis, and for the first time we have estimated the health state utility index scores of patients with FXS, in the context of the published HUI literature, helping to clarify the significance of this disorder,” continued Dr. Palumbo. “Further, we observed statistically significant improvements in the health state utility index scores of patients treated with Zygel in the 12-week exploratory Phase 2 FAB-C trial compared to baseline, suggesting a potential broad spectrum of benefit of the drug in the important domains of the ABC-CFXS that were incorporated into the utility index.”

Improvement in ABC-UI Score with Zygel Treatment

As shown in Figure 1 below, compared to their baseline scores, patients on Zygel experienced significant (P < 0.01) improvement in their mean ABC-UI beginning at week 4 and this improvement was maintained through weeks 8 and 12.

Figure 1. Mean ABC-UI Score at Each Timepoint during Treatment with Zygel (*P<0.01)

The authors of the poster concluded that:

  • Treatment with Zygel significantly improved health state utility index scores in pediatric and adolescent patients with FXS, suggesting a potential broad spectrum of benefit of Zygel in the important domains of the ABC-CFXS that were incorporated into the utility index;
  • The correlation of the ABC-UI scores with Clinical Global Impression of Severity (CGI-S) scores in these patients suggests that the ABC-UI appropriately reflects symptom severity in FXS; and
  • The estimated health state utility index score of 0.57 in patients with FXS enrolled in FAB-C appear to describe a poor baseline level of HRQoL, despite standard of care, highlighting the considerable impact of FXS symptoms on patient HRQoL.

Fragile X Syndrome Diagnosis and Patient Journey: The Caregiver’s Perspective

  • Poster number: 28
  • Poster presentation time: Tuesday, March 3 from 5:00 to 6:00 PM and Wednesday, March 4 from 5:00 to 7:00 PM.

“Children with Fragile X syndrome generally remain undiagnosed until approximately three years of age, and the path to diagnosis is complex,” said Dr. Palumbo. “These children also have a high prevalence of comorbid conditions which complicates the diagnosis. Today’s standard of care includes counseling and therapy and the use of traditional prescription medications that aren’t specifically indicated for FXS. This information supports the importance of testing for the disorder early in the diagnostic journey and bringing novel treatments that specifically treat the behavioral symptoms of FXS through the FDA approval process for the benefit of patients and their families.”

Core FXS clinical symptoms include social avoidance/withdrawal, anxiety, irritability, deficits in learning and cognition, and sleep difficulties. These symptoms are frequently compounded by comorbid conditions, including autism and attention-deficit/hyperactivity disorder. Parents often first recognize the initial symptoms and developmental delays, leading to subsequent clinical diagnosis of FXS utilizing genetic testing for mutations in the FMR1 gene. Early diagnosis of FXS is important to facilitate treatment and coordinate the multidisciplinary supportive care and educational interventions required to manage the symptoms of FXS. Unfortunately, diagnosis of FXS is often delayed. A 2008 study reported a delay of 24 to 26 months between initial symptoms and diagnosis, and mean age at diagnosis has remained delayed over time (32 months in 2018 vs 38 months in 2008).

Zynerba utilized a 30-minute, anonymized, quantitative online survey, conducted in the United States from May 3 to June 12, 2019, to characterize the patient journey in FXS surrounding diagnosis and clinical experiences. Thirty-five (35) predominantly female (80%) primary caregivers of children with FXS completed the survey. The children of these caregivers were 3 to 17 years of age, had a full FMR1 mutation, and exhibited socially avoidant behaviors.

Path to Diagnosis

The mean age of children with FXS at the time of diagnosis was 36 months. When asked to rate the top 3 factors prompting caregivers to schedule an initial visit with a physician, the most common were:

  1. Cognitive/intellectual developmental delays;
  2. Issues with speech and/or motor skills; and
  3. Social avoidance/social unresponsiveness.

Most caregivers scheduled an initial visit with a physician within 6 months of noticing symptoms (82.9%). The first physician seen was usually a primary care physician (family doctor or general pediatrician, 71.4%), but formal diagnosis of FXS was most often made by a specialist (80.0%), most frequently geneticists and neurologists/pediatric neurologists.

Current Experience with FXS

As shown in Figure 2 below, the most frequently experienced current symptoms of FXS were social avoidance and attention challenges. Most caregivers (85.7%) rated the severity of FXS at the time of the survey as severe (45.7%) or moderate (40.0%).

Figure 2. Current FXS Symptoms

Children of the surveyed caregivers were receiving a mean 1.94 treatments. Seventy-seven (77%) of children were currently receiving counseling/therapy; 46% were receiving traditional prescription treatment; and 31.4% were receiving nonprescription treatment/supplements. The most commonly received prescription medications were antidepressants/selective serotonin reuptake inhibitors (SSRIs) and stimulants. In addition, 77% of the children were reported to have comorbid conditions, the most common being autism spectrum disorder (66%), attention-deficit/hyperactivity disorder (26%), and sleep disorders (20%).

The authors concluded that:

  • The results of this survey expanded upon existing knowledge of the initial presentation/diagnosis and experience of FXS, finding an average age of 3 years at initial diagnosis, a high prevalence of comorbid conditions, and standard of care consisting primarily of counseling/therapy and traditional prescription medications; and
  • While caregivers of children with FXS often notice a variety of initial symptoms early and seek help from a health care professional, it is not until subsequent physician visits, often involving a specialist, that a formal diagnosis is made.

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.  

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

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

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