Zynerba Pharmaceuticals Announces Positive Top Line Results from Exploratory Open Label Phase 2 BRIGHT Trial of Zygel in Autism Spectrum Disorder

– The BRIGHT Trial Achieved Statistically Significant and Clinically Meaningful Improvements from Baseline in All Subscales of the Aberrant Behavior Checklist –

– Safety Data Reinforce Excellent Tolerability Profile of Zygel –

– Zynerba to host conference call and webcast today, May 27, 2020 at 8:30 am ET –

Devon, PA, May 27, 2020 — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced positive top line results from the exploratory, open label Phase 2 BRIGHT (An Open-Label Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Autism Spectrum Disorder) trial.

The trial was designed to assess the safety, tolerability and efficacy of Zygel™ in pediatric and adolescent patients with autism spectrum disorder (ASD). Zygel was administered to patients with moderate-to-severe symptoms of ASD as add-on therapy to their standard of care utilizing a variety of efficacy assessments. Key findings from the trial disclosed today include:

  • All five subscales of the Aberrant Behavior Checklist – Community (ABC-C) as well as the Parent Rated Anxiety Scale – Autism Spectrum Disorder (PRAS-ASD) showed both statistically significant and clinically meaningful improvements at 14 weeks of treatment from baseline;
  • The results observed in other efficacy outcome measures, including Clinical Global Impressions – Improvement scale (CGI-I), support the subscale results observed in the ABC-C;  
  • Zygel was well tolerated in this trial with no serious or severe adverse events reported.

“We are very encouraged by the compelling top line results of the BRIGHT trial and we expect to meet with the FDA to discuss the clinical pathway for developing Zygel for the treatment of behavioral symptoms of ASD in the second half of this year,” said Armando Anido, Zynerba’s Chairman and Chief Executive Officer. “Our goal is to develop Zygel for patients suffering from debilitating neuropsychiatric disorders including ASD, Fragile X syndrome, 22q and DEE. I want to thank the patients, families, physicians, clinical staff, and the Zynerba team for their support of this key study in ASD.”

Study Design
The 14-week exploratory, open label Phase 2 BRIGHT trial enrolled 37 patients with ASD at a single clinical site. The trial was designed to evaluate the safety, tolerability and efficacy of Zygel in children and adolescents ages three to 17 with ASD as confirmed by DSM-5 diagnostic criteria. Enrolled patients received weight-based doses of 250 mg or 500 mg daily of Zygel.

Patient Disposition and Baseline Demographics
Thirty-seven (37) patients were enrolled in the trial and are included in the safety analysis. One patient was lost to follow up with no post-treatment efficacy evaluation and, as a result, thirty-six (36) patients are included in the efficacy analyses. Twenty-eight (28) patients completed the 14-week trial. The discontinuation rate is consistent with other trials in ASD.

The mean age of patients enrolled in the trial was 9.2 years and thirty-four (92%) of the patients were male. Patients weighed between 15 and 108 kilograms (mean=41.6; median=30.2). The mean time to diagnosis in this population was 5.4 years. Using the Autism Diagnostic Observation Schedule (ADOS-2), 94% of enrolled patients had moderate-to-severe symptoms of ASD. The mean baseline ABC-C Irritability subscale score of 30.3 further supports the severity of the enrolled patient population. Ninety-two percent (92%) of patients entered the trial with the use of at least one underlying medication. Sixty-five percent (65%) of patients were on at least one psychotropic medication, for example, anti-depressants, anxiolytics and antipsychotics.

Top-line Efficacy Results
The trial evaluated multiple efficacy assessments, including the ABC-C, PRAS-ASD, Autism Parenting Stress Index, Autism Impact Measure (AIM), and Clinical Global Impression – Severity (CGI-S) and Improvement (CGI-I). The ABC-C irritability subscale was used as the basis for approval for the two atypical antipsychotics indicated for ASD.

Results from each of the subscales of the ABC-C after 14 weeks of treatment with Zygel are as follows:

ABC-C Subscale    Baseline
(n=36)
  Week 14
(n=28)
    Mean %
improvement
    p Value
                     
Irritability   30.3   18.2     39.1%     <0.0001*
Inappropriate Speech   7.4   5.2     42.5%     0.0002*
Stereotypy    12.3   7.9     39.1%     <0.0001*
Social withdrawal   25.1   16.5     36.4%     <0.0001*
Hyperactivity   37.0   23.9     35.6%     <0.0001*
         
*Statistically significant        

The results of other efficacy assessments reinforce the results demonstrated in the ABC-C. For example, patients on Zygel experienced a mean improvement of 46% at week 14 from a baseline score of 40.8 as measured by the PRAS-ASD (p<0.0001) and 57% of patients were assessed as “very much improved” or “much improved” at week 14 as measured by the CGI-I.

“I am very impressed with the improvements my patients made over the 14-week treatment period while receiving Zygel; the reduction in irritability, communication deficits, and repetitive movements were especially noteworthy since some of these are core autistic behaviors,” said Helen Heussler, FRACP, Associate Professor at Children’s Health Queensland, Medical Director Child Development and principal investigator in the BRIGHT trial. “The magnitude of effect on autistic behaviors in this trial is significant, including hyperactivity and stereotypy, which are among the most difficult behaviors to improve with therapeutic intervention. The results of this study strongly suggest the potential of this drug as an important treatment for ASD and I look forward to participating in future clinical studies with Zygel.”

Safety and Tolerability
Zygel was very well tolerated, and the safety profile was consistent with previously released data from other Zygel clinical trials. Less than half (49%) of the patients experienced any adverse event (whether unrelated or related to study drug), all of which were mild (75%) or moderate (25%). Only 14% of patients experienced an adverse event that was deemed to be treatment-related, all of which were application site-related; most were mild and transient. There were no severe or serious adverse events reported during the study. Eighteen (18) patients who completed the BRIGHT trial have rolled into the open label extension.

Conference call information
Zynerba management will host a live conference call and webcast today at 8:30 am Eastern Time to discuss the results of this clinical trial. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 6196218. To access the live webcast or the replay, visit the investor page of the Company’s website at http://ir.zynerba.com/. The webcast will be recorded and available on the Company’s website for 30 days.

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

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

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

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

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

Zynerba Pharmaceuticals Announces New Two-Year Data from Open Label Extension of the Phase 2 FAB-C Trial in Patients with Fragile X at 2020 American Academy of Neurology (AAN) Science Highlights Virtual Session

– Robust Response Sustained through Two Years of Treatment with Zygel™ in Patients from Phase 2 FAB-C Trial –

– Top Line Results of Pivotal CONNECT-FX Trial Expected Late in the Second Quarter of 2020 –

DEVON, Pa., May 26, 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 availability of a poster describing 116-week (two-year) data from the Phase 2 FAB-C (Treatment of Fragile X Syndrome Anxiety and Behavioral Challenges with CBD) trial of Zygel™ (CBD transdermal gel; ZYN002) in pediatric and adolescent patients with Fragile X syndrome (FXS). The data in the poster show that the statistically significant improvements from baseline that were observed at week 12 were sustained in each subscale score of the Aberrant Behavior Checklist for Fragile X (ABC-CFXS) through two years for patients who participated in the open label extension.

The poster entitled Cannabidiol Transdermal Gel for the Treatment of Fragile X Syndrome: Post Hoc Analysis and Pattern of Efficacy on Domains of the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS) Through 116 Weeks of Treatment is available at the 2020 American Academy of Neurology (AAN) Science Highlights Virtual Session. The Virtual Session is online at http://www.aan.com/2020science. A copy of the poster is also available on the Zynerba corporate website at http://zynerba.com/publications/

“It’s very exciting to see that the observed early benefits of Zygel appear to be sustained for over two years in patients who enrolled in the open label extension of FAB-C; these data suggest the potential for a sustained and measurable benefit for those patients who experience an early response,” said Zynerba’s Chief Medical Officer, Joseph M. Palumbo, MD, FAPA, MACPsych. “It’s also reassuring to see these responses in the context of a strong tolerability profile. We look forward to the results of our pivotal CONNECT-FX study in children and adolescents with FXS late this quarter.”

Open Label Phase 2 FAB-C Trial Background

The 12-week treatment results of the Phase 2 FAB-C trial were initially announced in September 2017. These data were published in the August 2nd, 2019 online edition of Journal of Neurodevelopmental Disorders. (Press release)

Twenty patients aged 6 to 17 years of age with Fragile X as confirmed by molecular documentation of FMR1 full mutation were enrolled in the open label FAB-C study. Zygel was added on to other medications being administered. At the completion of the 12-week study (Period 1), patients could enter an extension study (Period 2).

Thirteen patients who completed the Period 1 rolled into Period 2. One patient who withdrew during Period 2 for reasons unrelated to safety or efficacy had no efficacy data post week 12 and therefore was not included in the analyses. Ten patients exceeded two years of therapy.

Sustained Improvement in Core FXS Behaviors over Two Years of Treatment with Zygel

Statistically significant improvements from baseline were observed at week 12 in all six subscale scores of the ABC-CFXS in Period 1 and these statistically significant improvements were sustained through two years in subjects who entered Period 2. The persistence of effect over the two-year period is as follows.

Mean Percentage of Improvements from Baseline in ABC-CFXS Subscale Scores, Patients Who Entered Period 2

In addition, statistically significant improvements from baseline were observed at week 12 in the total score and all five subscale scores of ADAMS and these statistically significant improvements persisted to two years.

Responder Analysis

Zynerba performed responder analyses for patients achieving at least a 25% and 50% improvement from baseline for each subscale of the ABC-CFXS.

Maximal 25% responder rates for each ABC-CFXS domain at any visit in patients who completed Period 1 ranged from 72.2% to 83.3% and emerged by week 8 for all domains. Most patients who entered Period 2 met criteria for response at weeks 12 (≥66.7%) and 116 (≥80%).

Proportion of Patients with a ≥25% Improvement from Baseline ABC-CFXS Subscales for (A) Patients Who Completed Period 1 and (B) Patients Who Entered Period 2

Maximal 50% responder rates for each ABC-CFXS domain at any visit ranged from 50.0% to 77.8% in patients who completed Period 1 and were observed at week 8 for all domains except stereotypy. Among patients who entered Period 2, 50% responder rates ranged from 50% to 83.3% at week 12.  At week 116, the range of 50.0% responder rates was observed to be descriptively higher, ranging from 60% to 100% across the six ABC-CFXS domains.

Proportion of Patients with a ≥50% Improvement from Baseline ABC-CFXS Subscales for (A) Patients Who Completed Period 1 and (B) Patients Who Entered Period 2

Evidence of Global, Multi-domain, and Sustained Reduction in Behavioral Symptom Burden

Radar charts were created to visualize the proportional effect of Zygel across the six ABC-CFXS subscales. The boundaries of the polygon at screening and endpoint allow visualization of change across all domains cross-sectionally and over time. These radar charts suggest global and sustained reductions in severity with Zygel treatment in patients who entered Period 2.

Tolerability of Zygel over Two Years of Treatment

Zygel was well tolerated in the FAB-C trial over two years. Treatment-emergent adverse events (TEAEs) – any event occurring during a trial period whether unrelated or related to study drug – are common in children and expected over a two-year period. Of the 66 TEAEs reported in 19 patients, all were either mild (85%) or moderate (15%), and 91% were determined to be unrelated to treatment. No treatment-related TEAEs occurred in more than one patient. Only one serious adverse event (constipation) was reported over two years of treatment and was not related to treatment.  

The authors of the poster concluded that:

  • In this post hoc analysis, the majority of patients who completed Period 1 met important criteria for therapeutic response (≥25% or ≥50% improvement from baseline in ABC-CFXS domains) at weeks 4, 8, and 12 of the Phase 2 FAB-C trial; this response was sustained or continued to improve through two years in patients who entered Period 2;
  • Simultaneous visualization of change across all ABC-CFXS domains at baseline and endpoint through radar charts provided additional evidence for global, multi-domain, and sustained reduction in behavioral symptom burden among patients who entered Period 2;
  • Zygel was well tolerated through two years; all AEs were mild or moderate and most were considered unrelated to treatment; and
  • Together, these data may suggest evidence of the clinical efficacy and favorable safety and tolerability of Zygel in children and adolescents with FXS when added to stable standard of care therapies. A double‐blind, placebo‐controlled study of Zygel in FXS called CONNECT-FX is currently in progress and will extend the knowledge gained from this Phase 2 study.

About Fragile X Syndrome (FXS)

Fragile X syndrome is a rare genetic developmental disability that is the leading known cause of both inherited intellectual disability and autism spectrum disorder, affecting 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females. It is the most common inherited intellectual disability in males and a significant cause of intellectual disability in females, and the leading genetic cause of autism spectrum disorder (ASD). FXS is caused by a mutation in the Fragile X Mental Retardation gene (FMR1) located on the X chromosome and leads to dysregulation of the endocannabinoid pathway including the reduction in endogenous cannabinoids (2-AG and anandamide). The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. In the US, there are about 71,000 patients suffering with FXS.

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

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

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

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

Zynerba Pharmaceuticals Announces Presentation of Phase 2 BELIEVE Safety, Efficacy and Quality of Life Data in Developmental and Epileptic Encephalopathies (DEE) at the 2020 American Academy of Neurology (AAN) Science Highlights Virtual Session

Devon, PA, May 26, 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 on the safety, efficacy and quality of life results of the Phase 2 BELIEVE (Open Label Study to Assess the Safety and Efficacy of Zygel™ (ZYN002) Administered as a Transdermal Gel to Children and Adolescents with Developmental and Epileptic Encephalopathy) clinical trial. These data are being presented at the 2020 American Academy of Neurology (AAN) Science Highlights Virtual Session. The Virtual Session is online at http://www.aan.com/2020science. A copy of the posters are also available on the Zynerba corporate website at http://zynerba.com/publications/. The top line results of the 26-week Phase 2 BELIEVE trial were initially announced in September 2019. (Press release)

“These BELIEVE data continue to build on the strong safety and tolerability profile of Zygel that we’ve seen across our clinical trial programs, and provide evidence of its anti-seizure activity in children and adolescents suffering from developmental and epileptic encephalopathies, or DEEs,” said Zynerba’s Chief Medical Officer, Joseph M. Palumbo, MD, FAPA, MACPsych. “These data are particularly exciting because they also suggest its potential to improve behavioral, cognition and mood deficits in these children and adolescents, which may improve the quality of life for these children and their family.”

The first poster entitled Cannabidiol Transdermal Gel in Children and Adolescents with Developmental and Epileptic Encephalopathies: An OpenLabel Clinical Trial further describes the safety and efficacy of Zygel in children and adolescents with developmental and epileptic encephalopathies (DEE) who participated in the Phase 2 BELIEVE trial.

Forty-eight (48) patients with a mean age of 10.5 years were enrolled in BELIEVE and included in the safety analysis. Nearly three-quarters of patients (73%) had a diagnosis other than LGS or Dravet syndrome. Patients with DEE are medically fragile. Clinically important comorbid conditions were present in all patients and included gait and movement disorders (46%), sleep disturbances (40%), chronic respiratory conditions/infections (38%), and PEG/feeding tube (15%). The modified intent-to-treat (mITT) population comprised 46 patients; 33 patients in the mITT population had consciousness-impairing seizures (focal impaired awareness seizures [FIAS]; or convulsive, or tonic-clonic, seizures [TCS] including generalized tonic-clonic seizures [GTCS] and focal to bilateral tonic-clonic seizures [BTCS]) at baseline and constituted the population in which the primary efficacy endpoint was measured.

As described in the poster, the study met its primary efficacy objective: Over the BELIEVE 26-week treatment period, the median percentage reduction from baseline in monthly frequency of FIAS and TCS was 43.5% (primary efficacy endpoint). Reduction from baseline in monthly (28-day) seizure frequency was ≥44% from month two onwards using monthly seizure frequency normalized to 28 days (SF28). Monthly (28-day) reductions from baseline in seizure frequency ranged from 44% to 58% from month two of the treatment period onward. When analyzed by seizure type, the median reductions from baseline at month six for FIAS, GTCS, and BTCS were 45.3%, 59.5%, and 58.7%, respectively.

At six months of treatment in the BELIEVE trial, 62% of patients achieved a ≥35% reduction in FIAS and TCS from baseline, and 55% of patients achieved a ≥50 reduction in FIAS and TCS.

Percent of Patients With 35% and 50% Reduction in FIAS and TCS by Time Point, mITT Population With FIAS and/or TCS at Baseline (n = 33)

Safety

Zygel was well tolerated in this 26 week Phase 2 study. Adverse events (AEs) are common in this medically fragile patient population, and expected in a 26-week trial. All events in the six-month period, whether unrelated or related to study drug, were reported as AEs (e.g.: influenza, infections, scrapes, etc.). As a result and as anticipated, most patients experienced an adverse event during the 26-week BELIEVE trial. No safety signal was identified. The most common treatment-related adverse events occurred in only four patients each: application site dryness, application site pain, and somnolence (all four patients exhibiting somnolence were taking concomitant clobazam). Ten (10) patients reported a serious adverse event (SAE); most were infection-related and unrelated to study drug. Of the 10, two patients experienced an SAE that was determined to be possibly related to treatment (nonconvulsive status epilepticus and lower respiratory tract infection, both of which are common in patients with DEE). All SAEs recorded during the study resolved and did not require dose alteration. There were no clinically significant changes in vital signs, ECGs, or laboratory findings. No drug-related increases in liver function tests (LFTs) were observed.

The authors of the poster concluded that:

  • These data suggest meaningful reductions in FIAS and TCS with Zygel treatment beginning as early as month two and sustained through 26 weeks;
  • Zygel was well tolerated over 26 weeks of treatment in a medically fragile patient population of children and adolescents with DEEs;
  • The positive benefit/risk profile of Zygel in this trial supports further study in patients with DEEs and FIAS and TCS.

The second poster entitled Quality of Life and Qualitative Caregiver Assessments in Children and Adolescents with Developmental and Epileptic Encephalopathies Treated With Cannabidiol Transdermal Gel: An Open-Label Clinical Trial builds on the previously disclosed data suggesting the potential of Zygel to improve the quality of life of patients living with DEE.

The key assessments for Quality of Life (QoL) in the open label BELIEVE trial included the Epilepsy and Learning Disabilities Quality of Life (ELDQOL) scale – modified version, daily “good day/bad day” questionnaire, and qualitative caregiver assessment.

ELDQOL

Statistically significant reductions from baseline in mean ELDQOL-modified subscale scores for seizure severity, behavior, and mood were observed at week 26 (P < 0.01 for all measures).

Good Day/Bad Day Assessment

At month six, the combined proportion of “good day” and “fantastic day” reports increased from 52% at baseline to 70%, and the combined proportion of “terrible day” and “bad day” reports decreased from 12% at baseline to 4%.

Distribution of Good Day/Bad Day Ratings at Baseline and Month Six

Qualitative Caregiver Feedback

The qualitative caregiver assessment was administered to parents/caregivers for 43 patients. Improvement in summary measures of qualitative assessments was observed in most patients for most measures:

  • Any improvement: 84% (n = 36)
  • Improved vitality: 58% (n = 25)
  • Improvement in seizures: 51% (n = 22)
  • Improved cognition/concentration: 47% (n = 20)
  • Improved socially avoidant behaviors: 44% (n = 19)
  • Improvement in irritability: 33% (n = 14)
  • School improvement: 28% (n = 12)
  • Medical improvement: 14% (n = 6)

The most frequent positive qualitative statements were in the domains of (1) behavior, cognition, and mood, and (2) seizures. Some caregivers reported difficulty in applying gel (26%) and mild skin reaction issues (19%).

The authors concluded that treatment with Zygel may be associated with clinically meaningful improvements in social behaviors and cognitive symptoms and increased QoL in children and adolescents with DEEs and their families.

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

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

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

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

Zynerba Pharmaceuticals to Present at the Jefferies Virtual Healthcare Conference

Devon, PA, May 22, 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 Jefferies Virtual Healthcare Conference. The presentation will take place on Tuesday June 2, 2020 at 4:30PM ET. This meeting is being held virtually, and 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 Changes Annual Meeting of Shareholders to Virtual-Only Format in Response to COVID-19 Pandemic

Devon, PA, May 21, 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 due to public health guidance related to the coronavirus (COVID-19) pandemic and for the safety of participants its Annual Meeting has been changed to a virtual format only.

As previously announced, the Annual Meeting will be held on June 10, 2020 at 8:00 a.m. Eastern Time for shareholders of record as of the close of business on April 14, 2020. However, participants will not be able to attend the Annual Meeting in person. Both stockholders of record and street name stockholders will need to register in advance by following the instructions below in order to be able to attend the Annual Meeting via live audio webcast, submit their questions during the meeting and vote their shares electronically at the Annual Meeting.

Instructions for Participating in the Annual Meeting

In order to participate in the 2020 Annual Meeting via live audio webcast, you must register at www.viewproxy.com/zynerbapharm/2020 by 11:59 p.m. Eastern Time on June 7, 2020. If you are a registered holder, you must register using your name, address and phone number as it appears on your Notice of Internet Availability of Proxy Materials or your proxy card (if you received a printed copy of the proxy materials).  A Virtual Control Number will be assigned to you in a confirmation email following your registration.

If you hold your shares beneficially through a bank or broker, you must provide a legal proxy from your bank or broker during registration and you will be assigned a Virtual Control Number in order to vote your shares during the 2020 Annual Meeting. If you are unable to obtain a legal proxy to vote your shares, you will still be able to attend the 2020 Annual Meeting (but will not be able to vote your shares) so long as you demonstrate proof of stock ownership. Further instructions on how to attend the Annual Meeting via the internet, including how to demonstrate proof of stock ownership and how to vote your shares electronically at the Annual Meeting are posted on www.viewproxy.com/zynerbapharm/2020 under Frequently Asked Questions (FAQ).

The Annual Meeting live audio webcast will begin promptly at 8:00 a.m. Eastern Time on June 10, 2020. We encourage you to access the meeting prior to the start time. Online check-in will begin at 7:30 a.m. Eastern Time and you should allow ample time for the check-in procedures. We will have technicians available to assist you with access to the Annual Meeting.  If you encounter difficulties accessing the Annual Meeting live audio webcast during the check-in or meeting time, please email VirtualMeeting@viewproxy.com or call 1-866-612-8937.

Voting Methods

Whether or not shareholders plan to access the Annual Meeting electronically, the Company encourages you to vote in advance of the Annual Meeting by using one of the methods set forth in the proxy materials previously distributed, so that your vote will be counted even if you later decide not to attend the virtual Annual Meeting.  Shareholders who have already voted do not need to take any further voting action unless they wish to change their vote.

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 Reports First Quarter 2020 Financial Results and Operational Highlights

Topline Results from Pivotal CONNECT-FX and Phase 2 BRIGHT Trials Expected in the Second Quarter of 2020

Devon, PA, May 11, 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 first quarter ended March 31, 2020 and provided an overview of recent operational highlights.

“The past few months have been historic due to the outbreak of COVID-19, and we applaud everyone on the front line of this global pandemic, including healthcare workers, first responders, humanitarians, and our industry colleagues who are dedicated to the rapid development of treatments and vaccines,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “In response to the pandemic, Zynerba implemented important initiatives that we believe protect the safety of patients, clinical investigators and their staff, and our Zynerba employees and should allow us to conclude all three of our ongoing clinical trials and report top line results within our stated timelines.”

First Quarter 2020 and Recent Highlights

COVID-19 Preparedness

Implemented Plan to Prioritize the Safety of Patients and Caregivers, Minimize Risk of Supply Disruption, and Enable the Company to Achieve its Milestones

Zynerba and its contract research and manufacturing partners began contingency planning for the COVID-19 outbreak in January 2020 in conjunction with its clinical investigator sites. Helping to ensure the safety of clinicians and participating patients and their families is paramount; as such, the Company made early and actionable adjustments including remote site monitoring, patient visits using telemedicine where needed, direct shipment of study drug supplies to caregivers, and use of local clinical laboratories to collect study related blood samples. The approach is consistent with the U.S. Food and Drug Administration’s (FDA) Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic. At this time, we expect our timelines for delivery of top line results from all of our ongoing trials to not be impacted.

Zygel in Fragile X Syndrome (FXS)

Topline Results Expected from Pivotal CONNECT-FX Trial Late in the Second Quarter of 2020

Two hundred and twelve (212) children and adolescents with genetically-confirmed Fragile X syndrome (FXS) have been 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. Zynerba completed enrollment in February 2020 and 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 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 May 8, 2020, 96% of the 188 patients who have completed the 14-week blinded portion of the CONNECT-FX trial have enrolled in the open label extension trial.

Zygel in Autism Spectrum Disorder (ASD)

Topline Results from Phase 2 BRIGHT Trial of Zygel in ASD Expected in the Second Quarter of 2020

Thirty-seven (37) children and adolescents with moderate-to-severe ASD have been enrolled in the 14-week open label exploratory Phase 2 BRIGHT trial. The clinical trial is designed to evaluate the safety, tolerability and efficacy of Zygel as an add-on to standard-of-care for the treatment of pediatric and adolescent patients with ASD. The Company is utilizing a number of efficacy assessments, including the Aberrant Behavior Checklist, Parent Rated Anxiety Scale – Autism Spectrum Disorder, and Clinical Global Impression – Severity and Improvement, to identify the appropriate endpoint to use in future placebo-controlled trials. Zynerba completed enrollment in this trial in January 2020 and expects to report topline results 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)

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

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

Zygel in Developmental and Epileptic Encephalopathies (DEE)

Outcome of Discussions with FDA on Clinical Pathway for Zygel in DEE Expected in the Second Quarter of 2020

Based on the Phase 2 trial design and positive efficacy and safety results, Zynerba anticipates that it will pursue an indication that includes the 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. Zynerba expects to disclose the outcome of the interactions with the FDA in the second quarter of 2020.

First quarter 2020 Financial Results

As of March 31, 2020, cash and cash equivalents were $60.6 million, compared to $70.1 million as of December 31, 2019. Research and development expenses for the first quarter of 2020 were $6.9 million, including stock-based compensation of $0.5 million. General and administrative expenses for the first quarter of 2020 were $3.9 million, including stock-based compensation expense of $0.8 million. The net loss for the first quarter of 2020 was $12.3 million with basic and diluted net loss per share of $(0.53). Included in the net loss was $1.7M in non-cash foreign currency losses, which are primarily due to the remeasurement of our Australian subsidiary’s assets and liabilities, which are denominated in the local currency to the subsidiary’s functional currency, which is the U.S. dollar.

Financial Outlook

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; the timing and outcome of current and future legal proceedings; and the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS
(unaudited)

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED BALANCE SHEETS

Zynerba Contacts

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

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