SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 OR 15 (d)
of the Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): January 4, 2022
ZYNERBA PHARMACEUTICALS, INC.
(Exact Name of Issuer as Specified in Charter)
(State or Other Jurisdiction of
Incorporation or Organization)
80 W. Lancaster Avenue, Suite 300
Devon, PA 19333
(Address of Principal Executive Offices)
(Registrant’s Telephone Number, Including Area Code)
Check the appropriate box below if the Form 8–K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
|¨||Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)|
|¨||Soliciting material pursuant to Rule 14a–12 under the Exchange Act (17 CFR 240.14a–12)|
|¨||Pre–commencement communications pursuant to Rule 14d–2(b) under the Exchange Act (17 CFR 240.14d–2(b))|
|¨||Pre–commencement communications pursuant to Rule 13e–4(c) under the Exchange Act (17 CFR 240.13e–4(c))|
Securities registered pursuant to Section 12(b) of the Act:
|Title of each class||Trading Symbol(s)||Name of each exchange on which registered|
|Common Stock, $0.001 par value per share||ZYNE||The Nasdaq Global Market|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ¨
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
|Item 8.01||Other Events|
On January 4, 2022, Zynerba Pharmaceuticals, Inc. (the “Company”) issued a press release announcing clinical development updates for Fragile X syndrome, autism spectrum disorder, 22q11.2 deletion syndrome and developmental and epileptic encephalopathies. 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 January 4, 2022 and may use from time to time in presentations or discussions with investors, analysts or other parties.
|Item 9.01||Financial Statements and Exhibits|
|99.1||Press Release, dated January 4, 2022|
|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: January 4, 2022
|ZYNERBA PHARMACEUTICALS, INC.|
|By:||/s/ Suzanne Hanlon|
|Name: Suzanne Hanlon|
|Title: Secretary, Vice President and General Counsel|
Zynerba Pharmaceuticals Announces Clinical Development Updates for FXS, ASD, 22q and DEE
– Company plans to focus development of Zygel in FXS, ASD and 22Q –
– Company plans to initiate Phase 3 trial with Zygel™ in ASD in the second half of 2022 –
– Zynerba to hold conference call tomorrow, January 5 2022 at 9:00 a.m. ET –
DEVON, Pa., January 4, 2022 – Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today provided program updates for Fragile X syndrome (FXS), autism spectrum disorder (ASD), 22q11.2 deletion syndrome (22q) and developmental and epileptic encephalopathies (DEE). In addition to the continued clinical development of Zygel in FXS, the Company plans to focus on the development of Zygel in ASD and 22q. Based on Company research and strategic prioritization, the decision has been made to not move forward in DEE at this time.
“Committing to a Phase 3 development program for patients with autism spectrum disorder is a key step in the advancement of a new treatment option for patients who have high unmet medical needs and limited FDA approved treatment options,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “Data from our ASD clinical development program to date are compelling and, with a clear regulatory path toward potential approval, we are excited to move forward with this program.”
Anido added, “In addition, we are making good progress towards completing enrollment in the INSPIRE trial for patients with 22q11.2 deletion syndrome and expect to have topline results mid-year 2022. Putting resources behind a second indication beyond FXS and completing the INSPIRE trial is consistent with our mission of being a leader in rare and near-rare neuropsychiatric disorders, including FXS, ASD and 22q.”
Zygel in Fragile X Syndrome (FXS)
|§||The Company continues to expect topline results from RECONNECT, a confirmatory pivotal Phase 3 trial of Zygel in patients with FXS, in the second half of 2023.|
|§||The Company received written scientific advice from the European Medicines Agency (EMA) providing clarity and guidance on the clinical and regulatory requirements for the submission of a marketing authorization application (MAA) in the European Union (EU) for Zygel for the treatment of behavioral symptoms associated with FXS. Based on the EMA’s scientific advice, the Company believes that the successful completion of the current development program for Zygel in FXS will satisfy the requirements of an MAA in the EU.|
|§||Presented data at the BRAIN Foundation Synchrony 2021 Symposium describing how Zygel may provide therapeutic benefit in FXS through its effects on the endocannabinoid system. The presentation included results from the Phase 3 CONNECT-FX trial demonstrating that Zygel was superior to placebo in multiple analyses in the groups of patients with either ≥90% methylation or complete methylation (100%) of their FMR1 gene. Data also showed that in the Company’s ongoing open label extension study, Zygel continued to be well-tolerated, without reports of clinically significant changes in vital signs, ECGs or laboratories (including liver function) with a median length of treatment of 21 months. (Presentation)|
Zygel in Autism Spectrum Disorder (ASD)
|§||The Company plans to advance its program in ASD with two Phase 3 trials, the first of which is expected to start in the second half of 2022. The Company is finalizing the Phase 3 study protocol and will submit an Investigational New Drug application to the U.S. Food and Drug Administration (FDA) prior to commencing the pivotal program.|
|§||Previous discussions with the FDA included agreement on utilizing the irritability subscale of the Aberrant Behavior Checklist – Community (ABC-C) as the primary endpoint to support an indication for the treatment of irritability in ASD. This is the same primary endpoint utilized in the pivotal trials for the two existing FDA approved treatments for ASD.|
|§||In the Company’s exploratory, open-label Phase 2 BRIGHT trial in 37 children and adolescents 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, including the irritability subscale which showed a 39.1% improvement (p<0.0001). Furthermore, as previously reported, the 18 patients who continued through 38 weeks of treatment in the extension portion of the BRIGHT trial saw a 56.1% improvement in the ABC-C irritability subscale compared to baseline (p<0.0001).|
|§||In the United States, new estimates published in the U.S. Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report confirm an increasing trend in the prevalence of ASD, with approximately one in 44 eight year old children (or approximately 1.4 million children in total, if extrapolated to include children ages 3 to 17 years) identified with ASD. This increasing prevalence underscores the significant unmet medical need, as well as opportunity, to develop effective and well-tolerated treatment alternatives for these patients, especially considering that there are currently only two FDA approved treatments available for patients with ASD, each of which are antipsychotics.|
Zygel in 22q11.2 Deletion Syndrome (22q)
|§||The Company continues to screen and enroll patients for the 14-week open-label Phase 2 INSPIRE trial, and expects topline data mid-year 2022.|
|§||In the fourth quarter of 2021, the Company initiated an additional clinical site in the United States to assist completion of enrollment.|
|§||The Company plans to move forward in 22q as an orphan indication pending results from the ongoing Phase 2 INSPIRE trial in children and adolescents with genetically confirmed 22q, and subsequent discussion with the FDA on the regulatory path forward.|
Zygel in Developmental and Epileptic Encephalopathies (DEE)
|§||Feedback received from the FDA indicated that selecting a specific DEE syndrome will be required for a pediatric indication in epilepsy rather than evaluating improvements in certain seizure types across all DEEs. During 2021, the Company evaluated individual syndromes and conducted a feasibility study. Based on Company research and strategic prioritization, the decision has been made to maintain focus on other important neuropsychiatric behavioral conditions and not to pursue further development in DEE at this time.|
As a result of the pipeline update and anticipated additional clinical studies in ASD, management now believes the Company’s $75.6 million of cash and cash equivalents as of September 30, 2021 are sufficient to fund operations and capital requirements into the second half of 2023.
Conference Call Information
Zynerba management will host a live conference call and webcast tomorrow, January 5, 2022, at 9:00 a.m. Eastern Time to discuss updates to its clinical development plans. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 4181504. 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 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, and 22q11.2 deletion syndrome. 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.
Corporate Overview January 2022
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 THE COMPANY’S ONGOING OR PLANNED CLINICAL TRIALS IN FXS, ASD OR 22Q, OR IN ANY ADDITIONAL TRIALS, AND MAY NOT OTHERWISE SUPPORT FURTHER DEVELOPMENT IN A SPECIFIED INDICATION OR AT ALL; THE COMPANY’S PLANNED RECONNECT TRIAL MAY NOT BE DETERMINED TO BE SUFFICIENT TO SUPPORT A SUBMISSION FOR REGULATORY APPROVAL, INCLUDING AN NDA OR MAA; 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 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 Ʀ (Cannabidiol Gel) • Two Phase 3 clinical development programs ongoing/planned • Confirmatory RECONNECT pivotal trial in Fragile X syndrome (FXS) initiated September 2021, with topline results expected 2H 2023 • Plan to initiate pivotal Phase 3 program in autism spectrum disorder (ASD) 2H 2022 • Phase 2 study ongoing in 22q11.2 deletion syndrome (22q) with topline results expected mid - year 2022 • Experienced team with development and commercial expertise in transdermal delivery, orphan diseases, neurology, and psychiatry • Cash runway expected to be sufficient to fund operations and capital requirements into 2H 2023
Deep Clinical Pipeline & Near - term Milestones 4 Zygel Cannabidiol Gel *Orphan Drug and Fast Track designation **Orphan Drug designation Expected Milestones Topline results expected 2H 2023 Initiate Phase 3 program 2H 2022 Topline results expected mid - year 2022 Indication Preclinical Phase 1 Phase 2 Fragile X Syndrome (FXS)* Pivotal BRIGHT: Topline data released Autism Spectrum Disorder (ASD) INSPIRE: Ongoing RECONNECT: Pivotal confirmatory trial initiated 22q Deletion Syndrome (22q)**
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 • ~60% of patients are believed to fall into the completely methylated 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 with complete 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; 72 *) 250 mg daily 500 mg daily (weight - based dose) Placebo (n=102; 65 *) Mirrored Zygel administration 14 weeks Three through 17 years of age Open label extension (OLE) DBPC: Complete 48 months: Ongoing Patients randomized (1:1) to receive either Zygel or placebo * Patients with complete methylation of their FMR1 gene (137 total ~ 65% of trial population)
8 8 CONNECT - FX Results: Complete 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 Any Improvement Zygel vs placebo Social interaction 63% vs 37% ( p =0.005*) Irritable/Disruptive Behaviors 54% vs 33% ( p =0.027*) Social Avoidance/Isolation 58% vs 46% ( p =0.195) Overall behavior 61% vs 46% ( p =0.100) Clinically meaningful improvement on drug Significantly more pts achieved a clinically meaningful change Zygel vs placebo Social Avoidance (≥ 3 points) 56% vs 37% ( p =0.030*) Irritability (≥ 9 points) 37% vs 26% ( p =0.232) Clinical Global Impression of Improvement (anchored)** Any Improvement Zygel vs placebo 50% vs 36% ( p =0.128) ABC - C FXS Social Avoidance subscale 40% median percent improvement in socially avoidant behaviors ( p =0.027*) * Statistically significant ** Not specific to Social Avoidance Ad hoc analysis of 136 patients with complete methylation in efficacy population
CONNECT - FX: Safety 9 • 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
Confirmatory Pivotal Phase 3 10 R andomiz e d, Double - Blind, Pla c ebo - C on trolled, Multiple - Ce n ter, Effica c y and Safe t y Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome Zygel ( n~100 ; 80*) 250 mg daily ( ≤ 30kg) 500 mg daily (> 30kg ) 750 mg daily (> 50kg ) (weight - based dose) Placebo ( n~100 ; 80*) Mirrors Zygel administration 18 weeks Three through 17 years of age Open label extension (OLE) DBPC: Initiated 24 months: Planned Patients randomized (1:1) to receive either Zygel or placebo * Patients with complete methylation of FMR1 gene Trial Design
Primary endpoint • Change from baseline to end of treatment in ABC - C FXS Social Avoidance subscale in patients who have complete (100%) methylation of the FMR1 gene Secondary endpoints • Change from baseline to end of treatment in: • ABC - C FXS Irritability subscale in patients who have complete methylation • ABC - C FXS Social Avoidance subscale among all randomized patients (complete and partial methylation) • Percent of patients: • Any improvement on the Caregiver Global Impression of Change ( CaGI - C) for Social Interactions among patients with complete methylation • Rated as improved on the Clinical Global Impression - Improvement (CGI - I) scale among patients with complete methylation 11 Trial Design
Key study design elements • 18 week trial design will allow us to evaluate improvement in behavioral symptoms over time • Added a third dosing group of 750 mg for individuals >50 kg to maintain appropriate dosing levels for patients • Made trial more patient and family friendly than CONNECT – FX trial – virtual visits, fewer assessments administered, reduced frequency of lab and ECG tests, provided each family an electronic tablet for recording of assessments and skin diaries • Successful completion of current development program for Zygel in FXS expected to satisfy requirements of submitting a New Drug Application in the U.S. and a marketing authorization application in European Union 12 Trial Design
13 • 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 U.S. patents provide IP protection to 2038 ~1.4M U.S. children and adolescents with ASD
BRIGHT Phase 2 Trial in ASD 14 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)
15 15 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
16 *Lower values reflect improvement in each ABC - C subscale. Mean Scores and Percent Improvement Through Week 38* 31.6 7.4 12.7 27.6 36.1 14.3 4.0 6.2 14.0 19.5 13.3 3.8 4.8 10.9 16.8 0 10 20 30 40 Irritability Inappropriate Speech Stereotypy Social Withdrawal Hyperactivity Baseline Week 14 Week 38 ABC - C Subscale Score 61.2% ( P <0.0001) 59.6% ( P <0.0001) 53.4% ( P <0.0001) 56.1% ( P <0.0001) 50.5% ( P< 0.0001) n=18 BRIGHT Phase 2 Trial in ASD Statistically Significant Improvements from Baseline In All ABC - C Subscale Scores Sustained Through Week 38 1 1 18 of 27 patients that completed week 14 demonstrated ≥35% improvement in the ABC - C at week 14 and were allowed to continue treatment for additional 24 weeks.
• Well tolerated and consistent with previously released data at week 14 and week 38, compared to baseline • Approximately half the patients experienced a treatment - emergent adverse event (TEAE; any event, whether unrelated or related to study drug): 49% through week 14 and 54% at week 38 • Most were mild and transient • Only 14% and 19% of patients experienced a treatment - related AE at week 14 and week 38, respectively • All application site - related at week 14 • Most application site - related and 1 each of sleep disorder, increased appetite and frequent urination at week 38 • No severe or serious AEs reported during the 38 - week trial 17 Well Tolerated Safety Profile in BRIGHT Trial in ASD
Next Steps in ASD Program 18 • Discussions with FDA included agreement on utilizing the irritability subscale of the Aberrant Behavior Checklist – Community (ABC - C) as the primary endpoint to support an indication for the treatment of irritability in ASD • Same primary endpoint utilized in pivotal trials for existing FDA approved ASD treatments • Submit Investigational New Drug application specific to ASD • Finalize clinical protocol and recruit investigators to participate • Initiate pivotal Phase 3 program – first trial expected to start 2H 2022
19 • 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 INSPIRE trial underway in pediatric and adolescent patients with 22q • Two sites participating in Australia • Additional clinical site initiated in U.S. during 4Q 2021 to assist completion of enrollment 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 20 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
Next Steps in 22q Program 21 • Topline results from INSPIRE Phase 2 trial in children and adolescents with genetically confirmed 22q expected mid - year 2022 • The Company plans to move forward in 22q as an orphan indication pending results from the ongoing INSPIRE trial and subsequent discussion with the FDA on the regulatory path forward
Financial Strength 22 • Clean balance sheet • No debt, 41.2M shares outstanding (as of November 11, 2021) • Cash and cash equivalent position of $ 75.6M as of September 30, 2021 • Cash runway expected to be sufficient to fund operations and capital requirements into the second half of 2023
Deep Clinical Pipeline & Near - term Milestones 23 Zygel Cannabidiol Gel *Orphan Drug and Fast Track designation **Orphan Drug designation Expected Milestones Topline results expected 2H 2023 Initiate Phase 3 program 2H 2022 Topline results expected mid - year 2022 Indication Preclinical Phase 1 Phase 2 Fragile X Syndrome (FXS)* Pivotal BRIGHT: Topline data released Autism Spectrum Disorder (ASD) INSPIRE: Ongoing RECONNECT: Pivotal confirmatory trial initiated 22q Deletion Syndrome (22q)**
Corporate Overview January 2022