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Item 8.01 Other Events
On December 17, 2020, Zynerba Pharmaceuticals, Inc. (the “Company”) issued a press release announcing regulatory updates on Zygel in Fragile X syndrome. A copy of this press release is attached hereto as Exhibit 99.1 and incorporated herein by reference.
Attached as Exhibit 99.2 is a presentation that the Company will post on its website on December 17, 2020 and may use from time to time in presentations or discussions with investors, analysts or other parties.
Item 9.01 Financial Statements and Exhibits
The following exhibit is being filed herewith:
|99.1||Press Release, dated December 17, 2020.|
|99.2||Zynerba Pharmaceuticals, Inc. Presentation|
|104||The cover page from this Current Report on Form 8-K, formatted in Inline XBRL|
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Date: December 17, 2020
|ZYNERBA PHARMACEUTICALS, INC.|
|By:||/s/ Suzanne Hanlon|
|Name: Suzanne Hanlon|
|Title: Secretary, Vice President and General Counsel|
Zynerba Pharmaceuticals Provides Regulatory Update on Zygel™ in Fragile X Syndrome
- Single Trial to be Conducted in Patients with Fragile X Syndrome to Confirm Positive Results Seen in the Population of Responders in the CONNECT-FX Trial -
- Conference Call and Webcast Today, December 17, 2020 at 8:30 am ET -
DEVON, Pa., December 17, 2020 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today provided an update on its meeting with the U.S. Food and Drug Administration (FDA) regarding its Fragile X syndrome (FXS) program. The Company plans to conduct a double-blind, placebo-controlled pivotal trial in patients with FXS who have a highly methylated FMR1 gene to confirm the positive results observed in this population of responders in the CONNECT-FX trial. In the first half of 2021, Zynerba will review the trial design and protocol for the new trial through a Type C meeting with the FDA and expects to initiate the pivotal trial before the end of 2021. Zynerba believes that positive results from this confirmatory trial would be sufficient to support the submission of a New Drug Application (NDA) for Zygel™ in FXS.
“We believe that Zygel has the potential to meaningfully relieve the behavioral symptoms of the most impacted individuals with Fragile X syndrome. We are committed to bringing this important therapy to patients and their families within the Fragile X community,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We are thankful for our ongoing constructive dialogue with the FDA on our path forward to NDA submission. Completing the development of Zygel in FXS and preparing for a successful launch will be the primary focus of the Company.”
“The results reported in the analysis of children with a highly methylated FMR1 gene are a source of considerable hope for the patients and their families who are impacted by Fragile X syndrome,” said Linda Sorensen, Executive Director of the National Fragile X Foundation (NFXF). “Zynerba has been an important partner to the families of children with Fragile X. We thank them for their continued dedication and commitment to bringing an FDA-approved treatment to our families and look forward to helping with the recruitment of patients for this study.”
The Company’s development plan for Zygel in other indications includes the following:
|·||Developmental and epileptic encephalopathies (DEE): Evaluation of potential target indications is ongoing, and Zynerba now expects to finalize target syndrome selection in 2021 in one or more DEE syndromes.|
|·||22q11.2 deletion syndrome (22q): Zynerba expects to resume recruitment for the 14-week open label Phase 2 INSPIRE trial in children and adolescents with genetically confirmed 22q once COVID-19-related restrictions in Australia are eased. After recruitment has resumed, the Company will be able to provide a timeframe for completion of this trial.|
|·||Autism spectrum disorder (ASD): In the first half of 2021, Zynerba intends to discuss data supporting the potential efficacy of Zygel in ASD, including the results of the Phase 2 BRIGHT trial in children and adolescents with moderate-to-severe ASD with the FDA to determine the regulatory path forward.|
Financial Impact on Cash
The Company expects that its cash runway will extend into the beginning of 2023 as a result of these changes to its development plans.
Conference call information
Zynerba management will host a live conference call and webcast today at 8:30 am Eastern Time to discuss the recent FDA meeting and the regulatory pathway for Zygel in FXS. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 4088027. 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 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 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 planned clinical trial evaluating Zygel™ in patients with a highly methylated FMR1 gene may not confirm the results of the CONNECT-FX trial or may not be determined to be sufficient to support an NDA submission; 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.
William Roberts, Vice President, Investor Relations and Corporate Communications
Corporate Overview December 2020
Forward - Looking Statements 2 © 2020 Zynerba Pharmaceuticals, Inc. All rights reserved. Zynerba and Zygel are trademarks of Zynerba Pharmaceuticals, Inc. All other trademarks and registered trademarks are property of their respective owners. trademarks are property of their respective owners. THE STATEMENTS IN THIS PRESENTATION MAY INCLUDE FORWARD - LOOKING STATEMENTS WITHIN THE MEANING OF THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995. THESE STATEMENTS, AMONG OTHER THINGS RELATE TO THE FUTURE OPERATIONS, OPPORTUNITIES OR FINANCIAL PERFORMANCE OF ZYNERBA PHARMACEUTICALS, INC. 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, 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 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; AND THE COMPANY’S EXPECTATIONS REGARDING ITS ABILITY TO OBTAIN AND ADEQUATELY MAINTAIN SUFFICIENT INTELLECTUAL PROPERTY PROTECTION FOR ITS PRODUCT CANDIDATES. THESE AND OTHER RISKS ARE DESCRIBED IN OUR FILINGS WITH THE SECURITIES AND EXCHANGE COMMISSION, AVAILABLE AT WWW.SEC.GOV. ANY FORWARD - LOOKING STATEMENTS THAT THE COMPANY MAKES IN THIS PRESENTATION SPEAK ONLY AS OF THE DATE OF THIS PRESENTATION. 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 PRESENTATION .
Zynerba Pharmaceuticals (NASDAQ: ZYNE) 3 A Rare/Near - Rare Neuropsychiatric Company • Deep pipeline targeting high unmet medical needs; translating into multi - billion dollar market opportunity with Zygel™ (Cannabidiol Gel) • Focused on completing development of Zygel in Fragile X Syndrome (FXS) • Pre - planned ad hoc analyses of CONNECT - FX data identified patient population who appear to benefit from Zygel • As a result of meeting with FDA in 4Q2020, Zynerba plans to conduct a trial in patients with a highly methylated FMR1 gene to confirm positive results seen in CONNECT - FX responders • Continuing to pursue three additional neuropsychiatric indications: • 22q11.2 deletion syndrome (22q) – Phase 2 ongoing • Autism spectrum disorder (ASD) – Phase 2 complete • Developmental and epileptic encephalopathies (DEE) – Phase 2 complete • Experienced team with development and commercial expertise in transdermal delivery, orphan diseases, neurology, and psychiatry • Cash runway expected to be sufficient to fund operations into 2023
Deep Clinical Pipeline & Near - term Milestones 4 Zygel Cannabidiol Gel *Orphan Drug and Fast Track designation **Orphan Drug designation Expected Milestones Review trial design and protocol with FDA in 1H21; initiate confirmatory pivotal trial before the end of 2021 Discuss Phase 2 results and regulatory path forward with FDA in 1H2021 Completion of enrollment once COVID - 19 restrictions in Australia are eased Finalize target syndrome selection in 2021
Neuropsych Indications Differentiated Formulation delivers Cannabidiol through the epidermis and into the circulatory system Zygel (ZYN002) Cannabidiol Gel 5 Unique Mechanism of Action First & only patent - protected (2038), permeation - enhanced, pharmaceutically - produced cannabidiol gel Transdermal Cannabidiol modulates multiple receptors and mediates numerous pathways, including the endocannabinoid pathway Potential utility in rare / near - rare neuropsychiatric conditions
6 • Rare genetic developmental disability • Leading known cause of both inherited intellectual disability and ASD • No approved drugs indicated for FXS • Symptoms linked to deficiencies in the endocannabinoid system (ECS) • Mutation impacts FMR1 gene and causes ECS dysregulation, causing core cognitive, social, and behavioral symptoms of FXS • Easily identified mutation manifests as multiple CGG repeats in FMR1 (full mutation = >200 repeats) • U.S. patents provide IP protection to 2038 • FMR1 gene codes for production of FMRP* which is vital to synapse development • Methylation of FMR1 also plays a role in determining functionality of the gene • When methylation of FMR1 silences the gene, no FMRP is produced: Systems and processes affected by FMRP become dysregulated • These patients are generally the most severely impacted by the disorder: lower IQ, more impacted behaviors • ~60% of patients are believed to fall into this category Fragile X Syndrome (FXS) *FMR Protein; RNA - binding protein that helps regulate synaptic development and plasticity Role of FMR1 Methylation FXS FXS is routinely diagnosed by assessing (1) CGG repeats and (2) methylation status ~40K U.S. patients ≥90% FMR1 methylation ~70K U.S. patients with full mutation FXS
CONNECT - FX Trial Design 7 C linical study O f Ca NN abidiol in Childr E n and Adoles C en T s with F ragile X (CONNECT - FX) Zygel (n=110; 92*) 250 mg daily 500 mg daily (weight - based dose) Placebo (n=102; 77*) Mirrored Zygel administration Two week placebo period, followed by 12 weeks of treatment Three through 17 years of age Open label extension (OLE) DBPC: Complete 24 months: Ongoing Patients randomized (1:1) to receive either Zygel or placebo * Patients with ≥90% FMR1 methylation (167 total ~ 80% of trial population) included in pre - planned ad hoc analyses
CONNECT - FX 8 • Primary endpoint: • Change from baseline to end of treatment in ABC - C FXS Social Avoidance subscale • Key secondary endpoints: • Change from baseline to end of the treatment in • ABC - C FXS Irritability subscale score • ABC - C FXS Socially Unresponsive/Lethargic subscale score • Improvement in Clinical Global Impression (CGI - I) at end of treatment, anchored to FXS behaviors • Aligned with FDA’s ‘Voice of the Patient’ Guidance • Captured qualitative data on clinical relevance of FXS behaviors Endpoints and Data Collected
9 9 CONNECT - FX Results: ≥90% FMR1 Methylation Consistent Improvements Observed with Zygel vs. Placebo Caregiver reported behavioral change Clinician reported improvements in behavior Clinically meaningful improvements in behavior Primary endpoint Caregiver Global Impression of Change Social interaction ( p =0.002*) Irritable/Disruptive Behaviors ( p =0.028*) Social Avoidance/Isolation ( p =0.038*) Overall behavior ( p =0.052) Clinically meaningful improvement on drug Significantly more pts achieved a clinically meaningful change in Social Avoidance ( p =0.031*) and Irritability ( p =0.036*) with Zygel Clinical Global Impression of Improvement (anchored)** Trend toward statistical significance ( p =0.056) ABC - C FXS Social Avoidance subscale 40% median percent improvement in socially avoidant behaviors ( p =0.020*) * Statistically significant ** Not specific to Social Avoidance Full data available in June 30, 2020; July 22, 2020; and October 15, 2020 press releases
CONNECT - FX: Safety 10 • Zygel was very well tolerated • No serious or severe adverse events reported during the trial • All treatment - emergent adverse events (TEAEs; any event, whether unrelated or related to study drug) were mild or moderate • Most common treatment - related TEAE: application site pain • Zygel: 6.4%; placebo: 1.0% • Seven total psychiatric disorder TEAEs; 5 were in placebo group • Laboratory values for chemistry and hematology comparable between placebo and Zygel groups; no clinically relevant abnormalities in either group • No clinically significant changes to liver function tests
The Path Forward For Zygel in FXS 11 • Zynerba plans to conduct a single double blind, placebo controlled pivotal trial in patients with a highly methylated FMR1 gene to confirm results seen in CONNECT - FX responders • If results are positive, we believe this trial will be sufficient to support an NDA submission • Primary endpoint will be the Social Avoidance subscale of the ABC - C FXS • Trial design and protocol development ongoing for planned confirmatory trial in CONNECT - FX responder population • Type C meeting with FDA expected in 1H21 to review trial design and protocol • Initiation of confirmatory trial is expected before the end of 2021 and timing will be clarified after Type C meeting Next Steps Regulatory Update
12 • Near - rare disorder • Symptoms include irritability; anxiety, restricted, repetitive patterns of behavior; impairments in social communication; deficits in verbal and non - verbal communication; deficits in developing, understanding and maintaining relationships • Most diagnosed after age 4; can be diagnosed as early as age 2 ௗ • Significant unmet medical need • Accelerating rate of diagnosis but only two FDA approved products; both atypical antipsychotics • Neither address the key symptoms of social impairment and anxiety • Results from clinical trials of Zygel suggest spectrum of activity against core behaviors • Newer studies suggest ASD is linked to disruption of the ECS • Altered anandamide signaling may contribute to ASD - related social and communication impairments • ECS system modulates many cellular functions and molecular pathways altered in ASD • Cannabidiol may modulate the EC system and improve certain autism - related behaviors • Evidence suggests that cannabidiol may improve social avoidance and anxiety Autism Spectrum Disorder (ASD) Rationale for Developing Zygel in ASD ASD Recent U.S. patents provide IP protection to 2038 ~1M U.S. children and adolescents with ASD
BRIGHT Phase 2 Trial in ASD 13 Open - La B el Tole R ab I lity and Efficacy Study of ZYN002 Administered as a Transdermal G el to C H ildren and Adolescen T s with Autism Spectrum Disorder 37 pts with moderate - to - severe ASD enrolled Three through 17 years of age Screening Zygel 14 Weeks Weight based dosing: 14 weeks: COMPLETE 250 mg to 500 mg daily • Aberrant Behavior Checklist (ABC - C) • Parent Rated Anxiety Scale – Autism Spectrum Disorder (PRAS - ASD) • Autism Parenting Stress Index • Autism Impact Measure (AIM) 24 Weeks Open label extension • Clinical Global Impression – Improvement (CGI - I) and Severity (CGI - S) • Qualitative Caregiver Reported Behavioral Problems Survey Efficacy assessments (primary efficacy assessment = week 14 vs baseline)
14 14 Results of BRIGHT Phase 2 Trial Autism symptom frequency and impact Parental stress Qualitative caregiver assessments Severity of anxiety Primary efficacy objective ABC - C subscales % improvement Irritability: 39.1% ( p <0.0001*) Inappropriate Speech: 42.5% ( p =0.0002*) Stereotypy: 39.1% ( p <0.0001*) Social Withdrawal: 36.4% ( p <0.0001*) Hyperactivity: 35.6% ( p <0.0001*) Qualitative Caregiver Behavioral Problems Survey % Improvements Behavioral: 69% improved Social: 63% improved Emotional: 72% improved Autism Parenting Stress Index Mean improvement of 38.9% ( p<0.0001 *) Parent Rated Anxiety Scale for ASD (PRAS - ASD) Mean improvement of 46% ( p <0.0001*) * Statistically significant Autism Impact Measure (AIM) % improvement Atypical behavior: 34.1% ( p <0.001*) Communication: 19.7% ( p <0.001*) Peer interaction: 19.8% ( p <0.001*) Repetitive behavior: 32.1% ( p <0.0001*) Social reciprocity: 10.7% ( p =0.0053*) Statistically Significant Results at Week 14 Compared to Baseline Full data available in May 26, 2020 and October 15, 2020 press releases
• Well tolerated; consistent with previously released data • Fewer than half of patients experienced an adverse event (AE); most were mild and transient • Only 14% of patients experienced a treatment - related AE • All application site - related • No severe or serious AEs reported during the trial 15 Well Tolerated Safety Profile in BRIGHT Trial in ASD
Next Steps in ASD Program 16 • In 1H2021, Zynerba intends to discuss data supporting the potential efficacy of Zygel in ASD, including the results of the Phase 2 BRIGHT trial, with the FDA to determine the regulatory path forward • Present additional data at future medical meetings
17 • Rare disorder; most common contiguous gene deletion syndrome • Midline condition with abnormalities affecting palate, face, heart and other organs; surgically corrected in infancy • Neuropsychiatric illnesses (anxiety disorders, ASD) and learning disabilities common • 22q associated with increased anxiety, withdrawn behavior and social interaction problems • Early onset of neuropsychiatric symptoms disrupts development and quality of life, and heightens risk of later psychotic disorders • 25 - fold increased risk of developing schizophrenia • No drugs currently approved to treat 22q • Overlapping target symptoms in FXS and ASD have been shown to respond to Zygel in trials to date • Cannabidiol may treat neuropsychiatric symptoms due to activity as: • Modulator of endocannabinoid system • Agonist at serotonin 1A receptors • Antagonist at GPR55 receptors • Phase 2 trial underway in pediatric and adolescent patients with 22q • Enrollment delayed due to COVID - 19 restrictions in Australia; topline results timeline to be announced following lifting of restrictions 22q11.2 Deletion Syndrome (22q) Rationale for Developing Zygel in 22q 22q Orphan Drug designation for treatment of 22q ~81K U.S. patients with 22q
INSPIRE Phase 2 Trial in 22q 18 Target: 20 patients Six through 17 years of age Screening Zygel 14 Weeks Weight based dosing: 14 Weeks 250 mg to 500 mg daily Efficacy assessments (week 14 vs baseline) include: • Aberrant Behavior Checklist - Community (ABC - C) • Anxiety, Depression and Mood Scale (ADAMS) • Qualitative Caregiver Reported Behavioral Problem Survey • Clinical Global Impression – Severity and Improvement Assessing the I mpact of Zygel (Tra ns dermal Cannabidiol Gel) on P ediatr i c Behavio r al and E motional Symptoms of 22q11.2 Deletion Syndrome 24 Weeks Open label extension
19 • Group of rare / ultra rare childhood - onset epilepsies with impaired or regressed developmental progress • Cognitive impairment, psychiatric problems, and behavioral disturbances are phenotypic • Medically fragile population • Comorbidities include cerebral palsy, chronic respiratory infections, gait disturbances, movement disorders, scoliosis, and feeding problems • Includes wheelchair bound individuals, feeding tubes • Most common and debilitating seizure types: • Focal impaired - awareness (FIAS) – complex partial • Focal to bilateral tonic - clonic and generalized tonic - clonic (TCS) – convulsive seizures (CS) • Strong positive data observed in open label BELIEVE trial • Due to the heterogeneity of DEE patients, FDA suggests pursuing individual syndromes rather than considering DEE as a single condition • Evaluation of potential target indication(s) is ongoing • Expect to finalize target syndrome selection in 2021 in one or more DEE syndromes Developmental and Epileptic Encephalopathies (DEE) Developing Zygel in DEE DEE
BELIEVE Phase 2 Trial in DEE 20 Open La B el Study to Assess the Safety and E fficacy of ZYN002 Administered as a Transderma L Gel to Ch I ldren and Adol E scents with De V elopmental and E pileptic Encephalopathy 48 patients enrolled Three through 17 years of age Screening Maintenance 22 Weeks Titration 4 Weeks Open label extension Weight based dosing: Six months: COMPLETE Six months Zygel 250 mg to 1000 mg daily
21 21 Results of BELIEVE Phase 2 Trial Clinically Meaningful Improvements in FIAS / TCS and QoL vs. Baseline ≥35% and ≥50% responders Reductions in seizures in patients with ASD Improved Sleep Qualitative assessments Primary efficacy objective Mean % Reductions in Seizures Month 3 (n=33): 44% Month 6 (n=29): 51% Month 9 (n=18): 60% Month 12 (n=18): 73% ELDQOL Statistically significant reductions in subscale scores for seizure severity, behavior, and mood ( p <0.01) Mean % Reductions in Seizures: Comorbid ASD Month 3 (n=33): 45% Month 6 (n=29): 59% Month 9 (n=18): 67% Month 12 (n=18): 74% % of patients with ≥35% and ≥50% Reductions in FIAS and TCS ≥35% reductions Month 3: 58% Month 6: 62% Month 12: 89% Sleep Disturbance Scale for Children (SDSC) % Improvement Statistically significant improvements observed in Total Score: 36%; p =0.012 Disorders of initiating/maintaining sleep: 22%; p =0.006 Disorders of arousal/nightmares: 100%; p =0.031 Sleep wake transition disorder: 31%; p =0.030 ≥50% reductions Month 3: 46% Month 6: 55% Month 12: 83% Full data available in September 18, 2019 and December 4, 2020 press releases Caregiver Feedback Verbatim feedback included improved vitality, concentration and cognition, and school improvement
22 • Tolerability profile consistent with the safety database for Zygel • Most treatment - emergent adverse events (TEAEs) (any event, whether unrelated or related to study drug) were mild or moderate • Two SAEs deemed possibly drug - related (LRTI and status epilepticus) • No drug - related clinically significant changes in vital signs, ECGs, or laboratory findings BELIEVE Safety Zygel Well Tolerated over 12 months: No Safety Signal Identified
Financial Strength 23 • Clean balance sheet • No debt, 29.4 M shares outstanding (as of November 5, 2020) • Cash and cash equivalent position of $64.3M as of September 30, 2020 • Cash runway expected to be sufficient to fund operations and capital requirements into 2023
Deep Clinical Pipeline & Near - term Milestones 24 Zygel Cannabidiol Gel *Orphan Drug and Fast Track designation **Orphan Drug designation Expected Milestones Review trial design and protocol with FDA in 1H21; initiate confirmatory pivotal trial before the end of 2021 Discuss Phase 2 results and regulatory path forward with FDA in 1H2021 Completion of enrollment once COVID - 19 restrictions in Australia are eased Finalize target syndrome selection in 2021
Corporate Overview December 2020