ZYNE Zynerba Pharmaceuticals Inc.

3.77
-0.16  -4%
Previous Close 3.93
Open 3.97
52 Week Low 2.55
52 Week High 12.51
Market Cap $110,292,010
Shares 29,255,175
Float 25,923,811
Enterprise Value $39,081,859
Volume 808,967
Av. Daily Volume 1,833,415
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Drug Pipeline

Drug Stage Notes
Zygel ZYN002
22q11.2 Deletion Syndrome
Phase 2
Phase 2
Phase 2 trial delayed due to COVID-19.
Zygel ZYN002
Fragile X syndrome
Phase 2/3
Phase 2/3
Phase 2/3 trial did not meet primary endpoint - June 30, 2020.
Zygel ZYN002 - BRIGHT
Autism Spectrum Disorder (ASD)
Phase 2
Phase 2
Phase 2 data released May 27, 2020. Trial achieved statistically significant and improvements from in all subscales of the Aberrant Behavior Checklist.
ZYN002 BELIEVE 1
Developmental and Epileptic Encephalopathies (DEE)
Phase 2
Phase 2
Phase 2 top-line data released September 18, 2019. 10/46 patients reported a serious adverse event (SAE). Intends to meet with FDA 2Q 2020 to discuss path forward.
ZYN002
Adult Epilepsy Patients with Refractory Focal Seizures
Phase 2
Phase 2
Phase 2b trial initiation postponed until after the completion of childhood neuropsychiatric studies.
ZYN002 - STOP
Osteoarthritis
Phase 2
Phase 2
Phase 2 data released August 14, 2017 - primary endpoint not met. Noted January 2018 that development will be discontinued.
ZYN001
Fibromyalgia
Phase 2
Phase 2
Development to be discontinued - noted January 2018.
ZYN001
Peripheral Neuropathic Pain (PNP)
Phase 2
Phase 2
Development to be discontinued - noted January 2018.

Latest News

  1. DEVON, Pa., Aug. 10, 2020 (GLOBE NEWSWIRE) -- 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 second quarter ended June 30, 2020, and provided an overview of recent operational highlights.

    "We have made solid progress over the past few months towards our core mandate of developing important new therapies for patients suffering from underserved rare and near rare neuropsychiatric disorders," said Armando Anido, Chairman and Chief Executive Officer of Zynerba. "Regarding our pivotal CONNECT-FX data in Fragile X Syndrome, we continue to evaluate the data and believe that…

    DEVON, Pa., Aug. 10, 2020 (GLOBE NEWSWIRE) -- 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 second quarter ended June 30, 2020, and provided an overview of recent operational highlights.

    "We have made solid progress over the past few months towards our core mandate of developing important new therapies for patients suffering from underserved rare and near rare neuropsychiatric disorders," said Armando Anido, Chairman and Chief Executive Officer of Zynerba. "Regarding our pivotal CONNECT-FX data in Fragile X Syndrome, we continue to evaluate the data and believe that we have identified an important and severely impacted patient population that responded well to Zygel™ CBD gel. We also announced positive data from the Phase 2 BRIGHT trial in autism spectrum disorder during the quarter. We expect to meet with the U.S. Food and Drug Administration in the second half of this year to discuss the results from both trials and to clarify the paths forward."

    Second Quarter 2020 and Recent Highlights

    Zygel in Fragile X Syndrome (FXS)

    Reported Topline Results from Pivotal CONNECT-FX Trial; Pre-planned Ad Hoc Analysis Showed Statistically Significant Improvements (p=0.020) in Primary Endpoint in Children and Adolescents with Full Methylation of FMR1 Gene

    Zygel did not achieve statistical significance versus placebo in the primary or secondary endpoints in the full analysis set (n=210). However, a pre-planned ad hoc analysis of the most severely impacted patients in the trial (n=167), as defined by full methylation of the impacted FMR1 gene (FMet), demonstrated that Zygel achieved statistical significance in the primary endpoint of improvement at 12 weeks of treatment in the Social Avoidance subscale of the ABC-CFXS compared to placebo (p=0.020). The median improvement in this subscale after twelve weeks of treatment was 40% for patients on Zygel and 21% for patients on placebo. This group comprised 80% of the patients enrolled in the CONNECT-FX study and approximately 60% of the overall FXS patient population. Zygel was very well tolerated in CONNECT- FX, and the safety profile was consistent with previously released data from other Zygel clinical trials. Zynerba intends to meet with the FDA to discuss a regulatory path forward. (Press release)

    Presented CONNECT-FX Data Showing Statistically Significant Caregiver-Reported Improvements in Most Impactful FXS Behaviors at the 17th NFXF International Conference Research Roundup; Results Support Statistically Significant Results of Pre-planned Ad Hoc Analysis in FMet Patients

    Consistent with guidance from the FDA on capturing the voice of the patient in drug development, the Company collected additional qualitative data on the clinical relevance of various FXS behaviors to caregivers during CONNECT-FX. The results of the Qualitative Caregiver Reported Behavioral Survey indicate that caregivers found anxiety, socially avoidant behaviors (including elopement and isolation seeking), and disruptive behaviors (including aggression and temper tantrums) to be the most challenging. The results of the Caregiver Global Impression – Change survey show a broad shift toward global improvement from baseline to week 12 in FMet patients, with three of the four behavioral domains (social avoidance and isolation, irritable and disruptive behaviors, and social interactions) showing statistically significant improvements in favor of patients on Zygel compared to placebo and the fourth domain (overall behavior) trending toward significance. (Press release)

    Presented New Two-Year Data from the 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

    At the completion of the 12-week Phase 2 FAB-C study (Period 1), patients could enter an open label extension study (Period 2). Statistically significant improvements from baseline were observed at week 12 in all 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. In this 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 trial; this response was sustained or continued to improve through two years in patients who entered Period 2. Zygel was very well tolerated over two years. (Press release)

    Zygel in Autism Spectrum Disorder (ASD)

    Reported Positive Topline Results from Phase 2 BRIGHT Trial of Zygel in ASD; Statistically Significant Improvements from Baseline Observed in All Subscales of the Aberrant Behavior Checklist – Community (ABC-C)

    Thirty-seven children and adolescents with moderate-to-severe ASD were enrolled in the 14-week open label exploratory Phase 2 BRIGHT trial. The clinical trial was 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. All five subscales of the ABC-C showed both statistically significant (p<0.0002) and clinically meaningful improvements at 14 weeks of treatment from baseline. The results of other efficacy assessments reinforce the results demonstrated in the ABC-C, including a mean improvement of 46% at week 14 from baseline as measured by the Parent Reported Anxiety Scale for ASD (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 Clinical Global Impression - Improvement scale (CGI-I). Zygel was very well tolerated. (Press release)

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

    Recruitment into Phase 2 INSPIRE Trial of Zygel in 22q Delayed Due to the Impact COVID-19 in Australia

    Recruitment into the 14-week open label Phase 2 INSPIRE trial in children and adolescents (ages six through 17) with genetically confirmed 22q has been delayed due to the impact of COVID-19 in Australia and resulting travel restrictions. As a result of the uncertainty of the scope, duration and impact of the COVID-19 pandemic in Australia, the Company has withdrawn its guidance on the timing of data from this trial, and will provide updated guidance as soon as possible.

    Zygel in Developmental and Epileptic Encephalopathies (DEE)

    Presented Additional Phase 2 BELIEVE Safety, Efficacy and Quality of Life Data at the 2020 American Academy of Neurology (AAN) Science Highlights Virtual Session

    Over the Phase 2 BELIEVE 26-week treatment period, the median percentage reduction from baseline in monthly frequency of focal impaired awareness seizures (FIAS) and tonic clonic seizures (CS) was 43.5% (primary efficacy endpoint). Monthly (28-day) reductions from baseline in seizure frequency ranged from 44% to 58% from month two of the treatment period onward using monthly seizure frequency normalized to 28 days (SF28). 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. Statistically significant reductions from baseline in mean Epilepsy and Learning Disabilities Quality of Life (ELDQOL)-modified subscale scores for seizure severity, behavior, and mood were observed at week 26 (p<0.01 for all measures). 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%. (Press release)

    Outcome of Discussions with FDA on Clinical Pathway for Zygel in DEE Expected in the Third 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 FIAS and/or TCS, the most common and debilitating seizure types representing 75% to 80% of all seizures. Zynerba expects to announce the results of its ongoing discussions with the FDA on the clinical path forward in DEE in the third quarter of 2020.

    Second Quarter 2020 Financial Results

    As of June 30, 2020, cash and cash equivalents were $77.0 million, compared to $70.1 million as of December 31, 2019. In the second quarter of 2020, the Company sold and issued 5,682,784 shares of its common stock in the open market at a weighted-average selling price of $4.92 per share, for gross proceeds of $27.9 million and net proceeds, after deducting commissions and offering expenses, of $27.2 million under an a Controlled Equity Offering Sales Agreement with Cantor Fitzgerald & Co., Canaccord Genuity, LLC, H.C. Wainwright & Co. LLC and Ladenburg Thalmann & Co. Inc.

    Our Australian subsidiary, Zynerba Pharmaceuticals Pty Ltd, or the Subsidiary, is incorporated in Australia and is eligible to participate in an Australian research and development tax incentive program. As part of this program, the Subsidiary is eligible to receive a cash refund from the Australian Taxation Office, or ATO, for a percentage of the research and development costs expended by the Subsidiary in Australia. In July 2019, the Australian government's Department of Industry, Innovation and Science, or AusIndustry, responded to an Advance Overseas Finding, or AOF, application submitted by Zynerba that AusIndustry would allow certain research and development expenses incurred with respect to our product candidate Zygel outside of Australia to be eligible for the Australian research and development tax incentive program. During the year ended December 31, 2019, we recorded $8.3 million as an incentive and tax receivable and a corresponding credit to research and development expense for amounts expected to be received through the AOF for the period January 1, 2018 through December 31, 2019. As of June 30, 2020, incentive and tax receivables included $8.1 million related to the AOF. The reduction of $0.2 million versus December 31, 2019 was due to unrealized foreign currency losses related to the remeasurement of the Subsidiary's assets and liabilities. In June 2020, the ATO informed us that we may not qualify for the AOF program based on their interpretation of certain eligibility requirements. 

    We evaluate our eligibility under the Australian tax incentive programs as of each balance sheet date based on the most current and relevant data available. While a numeric standard does not exist, accounting practice generally considers an event that has a 75% or greater likelihood of occurrence to be probable. Although we continue to believe that we comply with the relevant conditions of the AOF program that were in place when we received our original approval from AusIndustry, based on this probability standard we have determined it is no longer probable that the AOF credits will be received. As a result, during the three months ended June 30, 2020, we recorded a full reserve against the $8.1 million AOF receivable. Discussions between the Company and the ATO are ongoing with respect to this issue.

    The following table summarizes research and development expenses for the three months ended June 30, 2020 and 2019.

      Three months ended June 30,
      2020 2019
    Research and development expenses (before impact of AOF)  9,242,146  8,223,783
    Amounts reserved against AOF refund  8,107,695  
    Total research and development expenses $17,349,841 $8,223,783

    Excluding the $8.1 million increase in research and development expenses for amounts reserved against the AOF refund, research and development expenses for the second quarter of 2020 were $9.2 million, including stock-based compensation expense of $0.5 million.

    General and administrative expenses for the second quarter of 2020 were $4.5 million, including stock-based compensation expense of $0.8 million.

    The net loss for the second quarter of 2020 was $20.3 million with basic and diluted net loss per share of $(0.78). During the three months ended June 30, 2020, we recognized a $1.5 million non-cash foreign exchange gain, which is 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 (the U.S. dollar).

    Financial Outlook

    Management believes that the current cash and cash equivalents is sufficient to fund operations and capital requirements into the fourth quarter of 2021.

    About Zynerba Pharmaceuticals, Inc.

    Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome, 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 expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company's ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company's clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company's product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration and foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company's ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company's reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company's product candidates the Company's ability to commercialize its product candidates; the size and growth potential of the markets for the Company's product candidates, and the Company's ability to service those markets; the Company's ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company's product candidates; the Company's expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the 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)

     

      Three months ended June 30,  Six months ended June 30,
       2020   2019   2020   2019 
    Operating expenses:        
    Research and development $17,349,841  $8,223,783  $24,232,634  $14,530,495 
    General and administrative  4,492,034   3,287,276   8,408,603   6,446,933 
    Total operating expenses  21,841,875   11,511,059   32,641,237   20,977,428 
    Loss from operations  (21,841,875)  (11,511,059)  (32,641,237)  (20,977,428)
    Other income (expense):        
    Interest income  26,601   439,201   228,285   790,152 
    Foreign exchange gain (loss)  1,482,513   (63,327)  (257,638)  (94,926)
    Total other income (expense)  1,509,114   375,874   (29,353)  695,226 
    Net loss $(20,332,761) $(11,135,185) $(32,670,590) $(20,282,202)
             
    Net loss per share - basic and diluted $(0.78) $(0.50) $(1.32) $(0.98)
             
    Basic and diluted weighted average shares outstanding  26,100,264   22,116,758   24,749,851   20,791,784 
             
    Non-cash stock-based compensation included above:        
    Research and development $534,900  $675,953  $1,045,376  $1,342,132 
    General and administrative  812,533   805,752   1,625,409   1,635,865 
    Total $1,347,433  $1,481,705  $2,670,785  $2,977,997 
     

     

     



    ZYNERBA PHARMACEUTICALS, INC.

    CONSOLIDATED BALANCE SHEETS

      (unaudited)  
      June 30, 2020 December 31, 2019
    Assets    
    Current assets:    
    Cash and cash equivalents $77,006,040  $70,063,242 
    Incentive and tax receivables  6,528,682   14,613,969 
    Prepaid expenses and other current assets  1,804,243   2,378,812 
    Total current assets  85,338,965   87,056,023 
    Property and equipment, net  641,263   362,724 
    Incentive and tax receivables  1,274,382    
    Right-of-use assets  227,529   345,849 
    Total assets $87,482,139  $87,764,596 
    Liabilities and Stockholders' Equity    
    Current liabilities:    
    Accounts payable $3,882,768  $4,740,981 
    Accrued expenses  8,936,501   7,073,506 
    Lease liabilities  237,406   243,677 
    Total current liabilities  13,056,675   12,058,164 
    Lease liabilities, long-term     109,689 
    Total liabilities  13,056,675   12,167,853 
         
    Stockholders' equity:    
    Common stock  29,255   23,211 
    Additional paid-in capital  257,902,423   226,409,156 
    Accumulated deficit  (183,506,214)  (150,835,624)
    Total stockholders' equity  74,425,464   75,596,743 
    Total liabilities and stockholders' equity $87,482,139  $87,764,596 
         

    Zynerba Contacts

    Jim Fickenscher, CFO and VP Corporate Development

    Zynerba Pharmaceuticals

    484.581.7483

    Will Roberts, VP Investor Relations and Corporate Communications

    Zynerba Pharmaceuticals

    484.581.7489

     

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  2. DEVON, Pa., Aug. 06, 2020 (GLOBE NEWSWIRE) -- 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 virtual 40th Annual Canaccord Genuity Growth Conference. The presentation will take place on Wednesday, August 12, 2020 at 4:30PM EDT. 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…

    DEVON, Pa., Aug. 06, 2020 (GLOBE NEWSWIRE) -- 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 virtual 40th Annual Canaccord Genuity Growth Conference. The presentation will take place on Wednesday, August 12, 2020 at 4:30PM EDT. 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

     

    Primary Logo

    View Full Article Hide Full Article
  3. DEVON, Pa., July 22, 2020 (GLOBE NEWSWIRE) -- Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, will present an overview of its Zygel™ (ZYN002) development program in Fragile X syndrome (FXS) and additional caregiver-reported data from its 14-week pivotal CONNECT-FX (Clinical study of Cannabidiol (CBD) in Children and Adolescents with Fragile X) trial during the 17th NFXF International Fragile X Conference Research Roundup. The multi-national, randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of Zygel™ CBD gel as a treatment for behavioral symptoms of Fragile X syndrome (FXS) in…

    DEVON, Pa., July 22, 2020 (GLOBE NEWSWIRE) -- Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, will present an overview of its Zygel™ (ZYN002) development program in Fragile X syndrome (FXS) and additional caregiver-reported data from its 14-week pivotal CONNECT-FX (Clinical study of Cannabidiol (CBD) in Children and Adolescents with Fragile X) trial during the 17th NFXF International Fragile X Conference Research Roundup. The multi-national, randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of Zygel™ CBD gel as a treatment for behavioral symptoms of Fragile X syndrome (FXS) in 212 patients; topline results were announced on June 30, 2020. (Press release).

    The presentation entitled, "Zygel (ZYN002) Development Program in Fragile X Syndrome" will take place at 3:45PM ET today, July 22, 2020. Additional information on the conference and registration are available here: https://fragilex.org/get-involved/international-fragilex-conference/. A copy of today's presentation will be made available prior to the time of presentation on the Zynerba corporate website at http://zynerba.com/publications/.

    "I am very pleased to participate in today's Fragile X Research Roundup on Fragile X Awareness Day," said Joseph M. Palumbo, MD, FAPA, MACPsych, Chief Medical Officer of Zynerba. "We believe that the caregiver data that we are presenting today further support the statistically significant improvement we achieved in the primary endpoint of social avoidance in patients with full methylation of their FMR1 gene. We look forward to discussing these and other data with the U.S. Food and Drug Administration as soon as possible regarding a potential regulatory path forward."

    Qualitative Caregiver Reported Behavioral Survey

    Consistent with guidance from the FDA on capturing the voice of the patient in drug development, the Company collected qualitative data on the importance of various FXS behaviors to caregivers entering the trial. Utilizing the Qualitative Caregiver Reported Behavioral Survey, caregivers were asked to describe their most important behavioral challenges at baseline. The results of the survey indicate that caregivers found anxiety, socially avoidant behaviors (including elopement and isolation seeking), and disruptive behaviors (including aggression and temper tantrums) to be the most challenging.

    Figure 1. Results of Qualitative Caregiver Reported Behavioral Survey is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/67243db8-e2cb-48f4-9ba9-71f82b6355c8

    Caregiver Global Impression - Change from Baseline to Week 12

    Using the Caregiver Global Impression - Change survey, caregivers were asked to complete a questionnaire rating how their child's behavior changed with respect to social avoidance and isolation, irritable and disruptive behaviors, social interactions, and the child's overall behavior at the end of the 12 week treatment period compared to the beginning of the trial, utilizing a seven point scale from ‘much worse' to ‘much better'. The results of this survey show a broad shift toward global improvement from baseline to week 12 for patients with full methylation of their FMR1 gene (FMet patients), with three of the four behavioral domains showing a statistically significant change in favor of patients on Zygel and the fourth domain trending toward significance.

    Figure 2. Results of Caregiver Impression - Change: Full Methylation Group is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/87e1db62-97e8-4dc6-9655-db036a073f20

    These statistically significant Caregiver Global Impression - Change data in socially avoidant behavior support the statistically significant improvement observed in the CONNECT-FX primary endpoint of social avoidance in FMet patients who received Zygel compared to placebo (p=0.020).

    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). 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 people suffering with FXS, approximately 60% of whom have full methylation of the FMR1 gene.

    FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including important effects on the endocannabinoid system, and most critically, codes for a protein called FMRP. This protein helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat. In most neurotypical people, the FMR1 gene correctly codes for the FMRP protein. In neurotypical individuals, there are CGG repeats, but these repeats only occur between 5 and 40 times. As a result, FMRP is manufactured at levels that enable control over behaviors like social avoidance and anxiety. In people with full mutation of the Fragile X gene, the CGG segment is repeated more than 200 times and in most cases causes the FMR1 gene to not function. However, the methylation of the FMR1 gene also plays a role in determining functionality of the gene. At greater than 90% methylation, which is considered "full methylation", the FMR1 gene is silenced, therefore, no FMRP is produced, and the systems and processes that are expected to be affected by FMRP become dysregulated.

    People with genetically confirmed full mutation Fragile X and full methylation of their FMR1 gene are generally the most severely impacted by the disorder.

    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

     

    Media contact

    Molly Devlin

    Evoke KYNE

    215.928.2199

    Primary Logo

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  4. - Study Did Not Achieve Statistical Significance in Primary or Key Secondary Endpoints in Full Analysis Set -

    - Achieved Statistical Significance on Primary Endpoint (p=0.020) in Pre-Planned Ad Hoc Analysis of Patients with Full Methylation of the FMR1 Gene Comprising 80% of the Study Population -

    - Zynerba to host conference call and webcast today, June 30, 2020 at 8:30 am ET -

    DEVON, Pa., June 30, 2020 (GLOBE NEWSWIRE) -- Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced top line results from the 14-week pivotal CONNECT-FX (Clinical study of Cannabidiol (CBD) in Children and Adolescents with…

    - Study Did Not Achieve Statistical Significance in Primary or Key Secondary Endpoints in Full Analysis Set -

    - Achieved Statistical Significance on Primary Endpoint (p=0.020) in Pre-Planned Ad Hoc Analysis of Patients with Full Methylation of the FMR1 Gene Comprising 80% of the Study Population -

    - Zynerba to host conference call and webcast today, June 30, 2020 at 8:30 am ET -

    DEVON, Pa., June 30, 2020 (GLOBE NEWSWIRE) -- Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced top line results from the 14-week pivotal CONNECT-FX (Clinical study of Cannabidiol (CBD) in Children and Adolescents with Fragile X) trial. The multi-national, randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of Zygel™ CBD gel as a treatment in for behavioral symptoms of Fragile X syndrome (FXS) in 212 patients.

    Zygel did not achieve statistical significance versus placebo in the primary endpoint of improvement in the Social Avoidance subscale of the Aberrant Behavior Checklist – Community FXS (ABC-CFXS). Zygel also did not demonstrate statistical significance versus placebo in the three key secondary endpoints, which were the change from baseline to the end of the treatment period in the Irritability subscale score of the ABC-CFXS, the Socially Unresponsive/Lethargic subscale score of the ABC-CFXS and Improvement in Clinical Global Impression (CGI-I).

    A pre-planned ad hoc analysis of the most severely impacted patients in the trial, as defined by patients having at least 90% methylation ("full methylation") of the impacted FMR1 gene, demonstrated that patients receiving Zygel achieved statistical significance in the primary endpoint of improvement at 12 weeks of treatment in the Social Avoidance subscale of the ABC-CFXS compared to placebo (p=0.020). This group comprised 80% of the patients enrolled in the CONNECT-FX study. The Company believes that full methylation occurs in approximately 60% of the overall FXS patient population. Based on this analysis, Zynerba intends to meet with the FDA regarding a regulatory path forward for Zygel.

    "This study identified a key population of patients who appear to benefit from treatment of their behavioral symptoms of FXS with Zygel," said Randi J. Hagerman, MD, an investigator in the clinical trial and Medical Director and Endowed Chair in Fragile X Research at UC Davis MIND Institute and Distinguished Professor at the Department of Pediatrics at UC Davis School of Medicine. "Zygel has the potential to be an important therapeutic option for the most severely impacted patients with Fragile X."

    "The results from CONNECT-FX identified a significant patient population who responded well to Zygel and may provide us with a pathway towards licensure," said Armando Anido, Zynerba's Chairman and Chief Executive Officer. "We intend to discuss the results of the study with the FDA as soon as possible. On behalf of the entire Zynerba team, I want to sincerely thank the patients, families and investigators who participated in this study as well as the National Fragile X Foundation, the FRAXA Research Foundation, and the Fragile X Association of Australia for their assistance in this study."

    CONNECT-FX Patient Disposition

    Two hundred and forty-five (245) patients with Fragile X syndrome, confirmed with the full mutation of the FMR1 gene, were enrolled at 21 clinical sites in the United States, Australia, and New Zealand. Unknown to the patients and their caregivers, all patients were given placebo during the first two weeks (called a "placebo run-in" which is often used in neuropsychiatric clinical trials), and as a result 33 patients were not randomized. The remaining 212 patients were included in the Intent-to-Treat (ITT) population (Zygel: n=110; placebo: n=102) and were randomized to receive either trial drug or placebo for an additional 12 weeks. One patient did not receive study medication so 211 patients are included in the safety analysis (Zygel: n=109; placebo: n=102.) One patient did not have a post-baseline efficacy measure, resulting in 210 patients in the full analysis set (Zygel: n=109; placebo: n=101).

    Baseline Demographics

    Select baseline demographics for the ITT population are as follows:

     PlaceboZygelTotal
    n102110212
    Age (years)9.89.69.7
    Sex – Males   
    n7881159
    %76%74%75%
    Weight – kg   
    Median34.336.835.7
    Range – Min, Max15.6, 104.714.6, 8714.6, 104.7
    >35 kg, %48.0%55.5%51.9%
    Baseline psychoactive medications, %66%57%62%

    Primary and Key Secondary Endpoints - Full Analysis Set

    The results of CONNECT-FX in the full analysis population for the primary and key secondary endpoints are summarized below.

     Placebo

    N=101
    Zygel

    N=109
       
    EndpointBaseline MeanWeek 12

    Mean

    Change
    Baseline

    Mean
    Week 12

    Mean

    Change
    Treatment

    Difference*
    Odds

    Ratio
    Treatment

    P-Value
    ABC-CFXS Social Avoidance Subscale7.24-2.297.12-2.68-0.39 NS
    ABC-CFXS Irritability Subscale27.65-4.1428.49-5.88-1.74 NS
    ABC-CFXS Socially Unresponsive / Lethargy Subscale12.82-3.1413.42-3.50-0.36 NS
    CGI-I at week 12 (Much and Very Much Improved)-15.9%-20.2% 1.33NS

    NS = Not statistically significant

    *A negative treatment difference demonstrates that Zygel patients improved versus placebo

    Pre-Planned Ad Hoc Analysis of Patients with Full Methylation of the FMR1 Gene

    The Company performed a pre-planned ad hoc analysis of the ITT population (n= 212) to evaluate the effect of Zygel versus placebo according to severity of baseline disease as defined by patients having full methylation of the impacted FMR1 gene. Patients with genetically confirmed full mutation Fragile X and full methylation of their impacted FMR1 gene are generally the most severely impacted by the disorder. Within the CONNECT-FX trial, this was corroborated with patients in the analysis at baseline having higher anxiety, lower IQ, lower adaptive function, and more severe autism as compared to patients without a fully methylated FMR1 gene. One hundred and sixty nine (169) patients met the criterion of full methylation of the FMR1 gene. One patient was not treated and one did not have a post-baseline efficacy measure, resulting in 167 patients (Zygel: n=91; placebo: n=76).

    Baseline demographics for patients with full methylation of the FMR1 gene are shown below.

     PlaceboZygelTotal
    n7792169
    Age (years)9.69.29.4
    Sex – Males   
    n5465119
    %70%71%70%
    Weight – kg   
    Median33.935.735.0
    Range – Min, Max15.6, 104.714.6, 87.014.6, 104.7
    >35 kg, %45.5%53.3%49.7%
    Baseline psychoactive medications, %65%54%59%

    Primary and Key Secondary Endpoints - Patients with Full Methylation of the FMR1 Gene

    The results of CONNECT-FX in the analysis set of patients with full methylation of the FMR1 gene across the primary and key secondary endpoints are summarized below.

     Placebo

    N=76
    Zygel

    N=91
       
    EndpointBaseline MeanWeek 12

    Mean

    Change
    Baseline

    Mean
    Week 12

    Mean

    Change
    Treatment

    Difference**
    Odds

    Ratio
    Treatment

    P-Value
    ABC-CFXS Social Avoidance Subscale7.18-1.997.12-2.99-1.0 0.020*
    ABC-CFXS Irritability Subscale28.00-4.1329.36-6.43-2.30 0.091
    ABC-CFXS Socially Unresponsive / Lethargy Subscale13.17-2.7413.30-3.91-1.17 0.135
    CGI-I at Week 12 (Any Improvement)-35.7%-51.1% 1.880.056

    *Statistically significant vs. placebo

    **A negative treatment difference demonstrates that Zygel patients improved versus placebo

    The median improvement in the Social Avoidance subscale of the ABC-CFXS after twelve weeks of treatment was 40.0% for patients on Zygel and 21.1% for patients on placebo.

    The interaction test of heterogeneity for the Social Avoidance subscale was statistically significant (p=0.002), which means that the difference in treatment effects between the subgroups was statistically significant.

    Safety Data

    Zygel was very well tolerated in CONNECT- FX, and the safety profile was consistent with previously released data from other Zygel clinical trials. No safety signal was identified. Approximately half (54%) of the 211 patients included in the safety population experienced a treatment emergent adverse event (any event, whether unrelated or related to study drug), all of which were mild or moderate. The frequency of treatment emergent adverse events was similar across treatment groups (58% of patients on Zygel, 50% of patients on placebo). There were no serious or severe adverse events reported during the study. There were seven total psychiatric disorder TEAEs, five of which were in the placebo group.

    Only 15 (7%) patients experienced a treatment-related adverse event (20 events total); 11 patients on Zygel experienced 14 treatment-related TEAEs, while four patients on placebo experienced six treatment-related TEAEs. The most common treatment-related TEAE was application site pain (Zygel: 6.4%; placebo: 1.0%).

    Laboratory values for chemistry and hematology were comparable between the placebo and Zygel treatment groups, and there were no clinically relevant abnormalities in either group. Specifically, there were no clinically significant liver function tests.

    Upcoming Corporate Milestones

    • Fragile X syndrome: Meet with the FDA to discuss CONNECT-FX results as soon as possible.
    • Developmental and epileptic encephalopathies (DEE): The results of discussions with FDA on the positive Phase 2 BELIEVE results and the clinical path forward are expected in 3Q2020.
    • Autism spectrum disorder (ASD): Zynerba intends to meet with FDA to discuss the positive Phase 2 BRIGHT trial results and clinical path forward in 2H2020.
    • 22q11.2 deletion syndrome (22q): As a result of COVID-19 travel restrictions in Australia, top line Phase 2 data from the INSPIRE trial are now expected in 4Q2020.

    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 9953448. To access the live webcast or the replay, visit the investor page of the Company's website at http://ir.zynerba.com/. The webcast will be recorded and available on the Company's website for 30 days.

    About Fragile X Syndrome (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). 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 people suffering with FXS, approximately 60% of whom have full methylation of the FMR1 gene.

    FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including important effects on the endocannabinoid system, and most critically, codes for a protein called FMRP. This protein helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat. In most neurotypical people, the FMR1 gene correctly codes for the FMRP protein. In neurotypical individuals, there are CGG repeats, but these repeats only occur between 5 and 40 times. As a result, FMRP is manufactured at levels that enable control over behaviors like social avoidance and anxiety. In people with full mutation of the Fragile X gene, the CGG segment is repeated more than 200 times and in most cases causes the FMR1 gene to not function. However, the methylation of the FMR1 gene also plays a role in determining functionality of the gene. At greater than 90% methylation, which is considered "full methylation", the FMR1 gene is silenced, therefore, no FMRP is produced, and the systems and processes that are expected to be affected by FMRP become dysregulated.

    People with genetically confirmed full mutation Fragile X and full methylation of their FMR1 gene are generally the most severely impacted by the disorder.

    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.  

    Statistical Analysis Method

    Inferential statistics for the primary endpoint are based on a linear mixed model for repeated measures (MMRM) including categorical effects for gender, region, treatment and week, treatment-by-week interaction, baseline score, and baseline score-by-week interaction. Inference for the primary endpoint in the subgroups defined by FMR1 status are also based on the primary model, and include the appropriate terms for subgroup interactions.

    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

     

    Media contact

    Molly Devlin

    Evoke KYNE

    215.928.2199

    Primary Logo

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  5. - 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 (GLOBE NEWSWIRE) -- 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…

    - 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 (GLOBE NEWSWIRE) -- 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.

    An infographic accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/b30a11af-12db-4428-9a7d-5b857a5ed25f

    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%).

    An infographic accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/1f21f88b-08af-47f8-b7da-af5223a2c0bf

    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.

    An infographic accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/a90b7fe1-1a26-4a3d-a12e-145546369a66

    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
     

    Media contact
    Molly Devlin
    Evoke KYNE
    215.928.2199

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