UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

 

FORM 8–K

 

 

 

CURRENT REPORT

Pursuant to Section 13 OR 15 (d)

of the Securities Exchange Act of 1934

 

Date of Report (Date of Earliest Event Reported): March 10, 2020

 

 

 

ZYNERBA PHARMACEUTICALS, INC.

(Exact Name of Issuer as Specified in Charter)

 

 

 

Delaware   001-37526   26-0389433
(State or Other Jurisdiction of
Incorporation or Organization)
  (Commission
File Number)
  (I.R.S. Employer
Identification No.)

 

80 W. Lancaster Avenue, Suite 300

Devon, PA 19333

(Address of Principal Executive Offices)

 

(484) 581-7505

(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 x

 

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. x

 

 

 

 

 

Item 2.02      Results of Operations and Financial Condition

 

On March 10, 2020, Zynerba Pharmaceuticals, Inc. issued a press release announcing its financial results and operational highlights for the fourth quarter and year ended December 31, 2019. A copy of this press release is furnished as Exhibit 99.1 hereto.

 

The information furnished pursuant to this Item 2.02, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and shall not be deemed to be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

 

Item 8.01      Regulation FD Disclosure

 

Attached as Exhibit 99.2 is a presentation, including certain financial information that the Company will post on its website on March 10, 2020 and may use from time to time in presentations or discussions with investors, analysts and other parties.

 

Item 9.01      Financial Statements and Exhibits

 

The following exhibits are being filed herewith:

 

(d) Exhibits

 

Exhibit
No.
  Document
     
99.1   Press Release, dated March 10, 2020.
99.2   Zynerba Pharmaceuticals, Inc. Presentation.

 

 

 

SIGNATURE

 

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: March 10, 2020

 

  ZYNERBA PHARMACEUTICALS, INC.
   
  By: /s/ Suzanne Hanlon
    Name: Suzanne Hanlon
    Title: Secretary, Vice President and General Counsel

 

 

 

 

Exhibit 99.1

 

 

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

 

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

 

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

 

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

 

Fourth Quarter 2019 and Recent Highlights

 

Zygel in Fragile X Syndrome (FXS)

 

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

Enrollment is complete with 212 patients randomized into CONNECT-FX, a pivotal, multi-national, randomized, double blind, placebo-controlled trial evaluating the efficacy and safety of Zygel in treating common behavioral symptoms of FXS. The primary endpoint is the change from baseline to the end of the treatment period in the Aberrant Behavior Checklist-Community FXS Specific (ABC-CFXS) Social Avoidance subscale. Key secondary endpoints are the change from baseline to the end of the treatment period in the ABC-CFXS Irritability subscale score and the ABC-CFXS Socially Unresponsive/Lethargic subscale score, and Clinical Global Impression - Improvement (CGI-I) at the end of the treatment period. The Company expects to report topline results late in the second quarter of 2020. If the results are positive, Zynerba intends to request a meeting with the FDA to determine the acceptability of the data as a basis for a New Drug Application (NDA) and to seek advice on preparation of the marketing authorization. The Company expects to submit its NDA for Zygel in FXS to the U.S. Food and Drug Administration (FDA) in the second half of 2020, with potential approval by mid-year 2021. (Press release)

 

 

 

 

 

Robust Enrollment Continues into Open Label Extension Study

 

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

 

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

 

The U.S. Patent and Trademark Office issued U.S. Patent No. 10,471,022 titled “Treatment of Fragile X Syndrome with Cannabidiol” which includes claims directed to a method of treating Fragile X syndrome, comprising transdermally administering 250 mg or 500 mg of CBD daily via a gel or cream. This new patent expires in 2038 and is part of an expanding intellectual property portfolio covering Zygel. (Press release)

 

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

 

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

 

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

 

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

 

Zygel in Autism Spectrum Disorder (ASD)

 

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

 

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Enrollment is complete in the Phase 2 BRIGHT trial assessing the safety, tolerability and efficacy of Zygel for the treatment of pediatric and adolescent patients with ASD. The 14-week trial is evaluating the efficacy and safety of Zygel in 37 children and adolescents (ages four through 17) with moderate-to-severe ASD. The efficacy assessments include the Aberrant Behavior Checklist, Parent Rated Anxiety Scale – Autism Spectrum Disorder, Autism Impact Measure, and Clinical Global Impression – Severity and Improvement. The mean age of the 37 patients enrolled in the BRIGHT trial is 9.2 years. Ninety-two (92) percent of the enrolled patients are male, accurately reflecting the overall prevalence and gender ratio of moderate-to-severe ASD in the United States and in other studies. Zynerba expects to report topline results from this study in the second quarter of 2020. (Press release)

 

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

 

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

 

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

 

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

 

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

 

Phase 2 Open Label Trial of Zygel in 22q Ongoing; Data Now Expected in the Third Quarter of 2020

 

The Company is conducting the 14-week Phase 2 INSPIRE trial to evaluate the safety, tolerability and efficacy of Zygel in approximately 20 children and adolescents (ages six through 17) with genetically-confirmed 22q. The efficacy assessments include the Aberrant Behavior Checklist-Community (ABC-C), the Anxiety, Depression and Mood Scale (ADAMS), the Qualitative Caregiver Reported Behavioral Problem Survey, and Clinical Global Impression – Severity and Improvement. Zynerba now expects to report topline results from this study in the third quarter of 2020.

 

Zygel in Developmental and Epileptic Encephalopathies (DEE)

 

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

 

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

 

Corporate

 

Enhanced Senior Management Team

 

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

 

Fourth quarter and full year 2019 Financial Results

 

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

 

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

 

Financial Outlook

 

The Company’s cash and cash equivalents as of December 31, 2019 was $70.1 million. Management believes that the cash runway is sufficient to fund operations and capital requirements beyond the expected NDA submission and potential approval of Zygel in FXS and into the second half of 2021.

 

4

 

 

 

About Zynerba Pharmaceuticals, Inc.

 

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

 

Cautionary Note on Forward-Looking Statements

 

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

 

5

 

 

 

 

 

ZYNERBA PHARMACEUTICALS, INC.

CONSOLIDATED STATEMENTS OF OPERATIONS

 

    (unaudited)              
    Three months ended December 31,     Year ended December 31,  
    2019     2018     2019     2018  
Revenue   $     $ 86,000     $     $ 86,000  
Operating expenses:                                
Research and development     7,457,953       4,876,162       20,384,049       27,245,043  
General and administrative     3,958,211       3,256,044       13,935,761       13,238,787  
Total operating expenses     11,416,164       8,132,206       34,319,810       40,483,830  
Loss from operations     (11,416,164 )     (8,046,206 )     (34,319,810 )     (40,397,830 )
Other income (expense):                                
Interest income     295,140       321,621       1,522,138       961,323  
Foreign exchange gain (loss)     406,033       (65,658 )     (145,911 )     (474,668 )
Total other income     701,173       255,963       1,376,227       486,655  
Net loss   $ (10,714,991 )   $ (7,790,243 )   $ (32,943,583 )   $ (39,911,175 )
                                 
Net loss per share - basic and diluted   $ (0.46 )   $ (0.44 )   $ (1.50 )   $ (2.61 )
                                 
Basic and diluted weighted average shares outstanding     23,191,428       17,616,373       22,000,203       15,308,886  
                                 
Non-cash stock-based compensation included above:                                
Research and development   $ 456,420     $ 819,715     $ 2,371,998     $ 3,087,498  
General and administrative     751,253       778,915       3,189,897       3,538,245  
Total   $ 1,207,673     $ 1,598,630     $ 5,561,895     $ 6,625,743  

 

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ZYNERBA PHARMACEUTICALS, INC.

CONSOLIDATED BALANCE SHEETS

 

    December 31, 2019     December 31, 2018  
Assets                
Current assets:                
Cash and cash equivalents   $ 70,063,242     $ 59,763,773  
Incentive and tax receivables     14,613,969       3,444,620  
Prepaid expenses and other current assets     2,378,812       3,747,087  
Total current assets     87,056,023       66,955,480  
Property and equipment, net     362,724       371,963  
Right-of-use assets     345,849        
Total assets   $ 87,764,596     $ 67,327,443  
Liabilities and Stockholders' Equity                
Current liabilities:                
Accounts payable   $ 4,740,981     $ 4,461,567  
Accrued expenses     7,073,506       5,264,215  
Lease liabilities     243,677        
Total current liabilities     12,058,164       9,725,782  
Lease liabilities, long-term     109,689        
Total liabilities     12,167,853       9,725,782  
                 
Stockholders' equity:                
Common stock     23,211       17,627  
Additional paid-in capital     226,409,156       175,476,075  
Accumulated deficit     (150,835,624 )     (117,892,041 )
Total stockholders' equity     75,596,743       57,601,661  
Total liabilities and stockholders' equity   $ 87,764,596     $ 67,327,443  

 

Zynerba Contacts

 

Jim Fickenscher, CFO and VP Corporate Development

Zynerba Pharmaceuticals

484.581.7483

fickenscherj@zynerba.com

 

Will Roberts, VP Investor Relations and Corporate Communications

Zynerba Pharmaceuticals

484.581.7489

robertsw@zynerba.com

 

  7  

 

Exhibit 99.2

 

Corporate Overview March 10, 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 focused on high unmet medical needs; translating into multi - billion dollar market opportunity with Zygel ™(CBD gel) • Four clinical shots on goal: FXS, DEE, ASD, 22q • Enrollment complete in pivotal CONNECT - FX FXS trial and in Phase 2 BRIGHT ASD study • Topline data expected from both trials in 2Q2020 • Experienced team • Proven development and commercialization track record in transdermal delivery, orphan diseases, neurology, psychiatry • Well capitalized • Cash runway expected into the second half of 2021 - beyond the expected NDA filing and potential approval in FXS • Multiple expected near term milestones

 

Deep Clinical Pipeline 4 *Orphan Drug Designation Zygel Cannabidiol Gel Expected Milestones Topline pivotal data in late 2Q2020 Topline Phase 2 data in 2Q2020 Topline Phase 2 data in 3Q2 020 Meet with FDA in 1H2020 to discuss clinical path forward

 

Neuropsych Indications Differentiated F ormulation delivers CBD through the epidermis and into the circulatory system Zygel (ZYN002) Cannabidiol (CBD) Gel 5 Unique MOA First & only patent - protected, permeation - enhanced, pharmaceutically - produced CBD gel Transdermal CBD modulates multiple receptors and mediates numerous pathways, including the endocannabinoid pathway Potential utility in rare / near - rare neuropsychiatric conditions FDA Fast Track and Orphan Drug designations in FXS

 

Fragile X Syndrome (FXS) 6

 

Fragile X Syndrome (FXS) Overview 7 • Rare genetic developmental disability • L eading known cause of both inherited intellectual disability and autism spectrum disorder • Symptoms linked to deficiencies in the endocannabinoid (EC) system • System of neurotransmitters regulating emotional responses, behavioral reactivity to context, social interaction • FMR1 mutation causes dysregulation of the EC system • Results in core cognitive, social, and behavioral symptoms of FXS • CBD may modulate EC system • Increases availability of endocannabinoids (anandamide, 2 - AG) by inhibiting metabolism • Affects ~71K people in U.S. • No approved drugs indicated for FXS

 

Day 1 to Week 6 Week 7 to 12 Up to 24 months FAB - C Open Label Phase 2 Trial Design 8 Treatment of F ragile X Syndrome A nxiety and B ehavioral C hallenges with CBD Titration Maintenance Screening Open label extension D osing initiated at 50 mg Zygel daily; may be titrated up to 250 mg Zygel daily D oses of Zygel: 50 mg, 100 mg, or 250 mg daily 20 patients enrolled • Patients continue on maintenance dose • Physician can titrate up or down Period 1: COMPLETE Period 2

 

Data From Three Month FAB - C Phase 2 Trial 9 0 10 20 30 40 50 60 70 Social Avoidance Irritability Socially Unresponsive / Lethargic Inappropriate Speech Stereotypy Hyperactivity Month 3 (n=18) Baseline: 18.2 Baseline: 14.5 Baseline: 8.7 Baseline: 5.1 Baseline: 7.9 Baseline: 6.1 41.8% 52.9% 54.9% 32.4% 59.5% 42.6% P=0.0005 P=0.0096 P=0.0034 P=0.0018 P=0.0006 P=0.0237 Mean % Improvement from Baseline Month Three: ABC - C FXS Mean Score Percent Improvement in Behavioral Symptoms of FXS Data reported at the American Psychiatric Association (APA) meeting, May 2019

 

Third Party Data* Suggest PBO Rate of 10 to 18 Percent 10 0 10 20 30 40 50 60 Zygel 0 10 20 30 40 50 Zygel 0 10 20 30 40 50 60 Zygel 0 10 20 30 40 50 Zygel 0 10 20 30 40 50 60 Zygel 0 10 20 30 40 Zygel Socially Unresponsive / Lethargic Does not pay attention Inappropriate Speech Repeats words / phrases Stereotypy Repetitive movements Hyperactivity Disrupts group activities Social Avoidance Seeks isolation Irritability Temper tantrums 0 10 20 30 40 50 60 Ganaxolone Placebo 0 10 20 30 40 50 60 Ganaxolone Placebo 0 10 20 30 40 50 Ganaxolone Placebo 0 10 20 30 40 50 60 Ganaxolone Placebo 0 10 20 30 40 Ganaxolone Placebo Baseline: 18.2 Baseline: 18.9 Baseline: 14.5 Baseline: 13.9 Baseline: 8.7 Baseline: 6.6 Baseline: 5.1 Baseline: 3.5 Baseline: 7.9 Baseline: 7.4 Baseline: 6.1 Baseline: 6.0 3.1 19.6 13.9 6.9 7.1 6.3 41.8% 17.9% 16.9% 32.4% 11.5% 18.7% 52.9% 17.4% 15.2% 54.9% 9.7% 31.4% 59.5% 9.9% 23.0% 42.6% 15.9% 15.0% * Ligsay , A., Van Dijck , A., Nguyen, D. V., Lozano, R., Chen, Y., Bickel, E. S., et al. (2017). A randomized double - blind, placebo - controlled trial of ganaxolone in children and adolescents with fragile x syndrome. Journal of Neurodevelopmental Disorders, 9:26. 0 10 20 30 40 50 Ganaxolone Placebo Baseline: 18.9 FAB - C ABC - C FXS Subscales

 

Three Month FAB - C Data vs. 12 Months of Treatment 11 0 10 20 30 40 50 60 70 80 90 Social Avoidance Irritability Socially Unresponsive Hyperactivity Stereotypy Inappropriate Speech Month 3 (n=12) Month 12 (n=9) 57.9* 51.1* 65.7* 36.7* 60.8* 56.5* *P ≤ 0.05 Mean % Improvement from Baseline 77.2* 59.2* 72.2* 40.4* 64.9* 56.5* Improvements in Patients Completing 12 Months Data reported at the American Psychiatric Association (APA) meeting, May 2019 Sustained Improvements in FXS Behavioral Symptoms Through 12 Months of Treatment

 

FAB - C Open Label Phase 2 Trial 12 • Well tolerated, consistent with previously reported data; no SAEs • No clinically meaningful trends in vital signs, ECG, or clinical safety labs including LFTs; no THC detected in plasma • Discontinuations • Two siblings discontinued in Period 1 • One for worsening of pre - existing eczema (not considered Tx - related ) • One due to administrative reasons • Three patients discontinued in Period 2 (administrative reasons; non - compliance) • Little to no redness at application site • One patient developed moderate application site rash (resolved, did not recur); remains in the study • TEAEs mild or moderate • Most common: Gastroenteritis (14%), URTI (12%) • All resolved during study period Zygel Safety Summary Through 12 Months

 

FAB - C Open Label Phase 2 Trial 13 Estimating the Health State Utility (HUI) Score for FXS and Potential Benefit of Treatment with Zygel Mean ABC - UI Score at Each Timepoint during Treatment with Zygel (*P<0.01) Data reported at the American Society for Experimental Neurotherapeutics (ASENT) 2020 Meeting 1 Kerr C et al. Qual Life Res .2015;24(2 ):305 - 314 • An HUI specific to FXS - the ABC - UI - was derived from the ABC - C FXS to measure the health - related quality of life ( HRQoL ) benefit of treatments for FXS 1 • HUI, measured on a scale of 0 to 1, are used in clinical and economic analyses of therapies with potential impact on HRQoL • Analysis evaluated the potential benefit of Zygel on the ABC - UI in FXS through post hoc analysis of data from FAB - C • Patient - level data from FAB - C were mapped to the ABC - UI algorithm to generate a utility index score for each patient • Mean ABC - UI for FXS patients estimated to be 0.57 at baseline • Reflects important impact of FXS on HRQoL despite children and adolescents being maintained on standard of care for FXS • Suggests impact similar or worse than other debilitating pediatric conditions • Compared to baseline, patients receiving Zygel experienced significant (P < 0.01) and sustained improvement in their mean ABC - UI from week 4 to 12

 

CONNECT - FX: A Pivotal Trial In FXS 14 C linical study O f Ca NN abidiol (CBD) in Childr E n and Adoles C en T s with F ragile X (CONNECT - FX) Zygel 250 mg daily 500 mg daily (weight - based dose) Placebo Mirrors Zygel administration Patients randomized (1:1) to receive either Zygel or placebo Treatment Target: 204 patients; 212 enrolled Three through 17 years of age Screening Open label extension 14 weeks 12 months Enrollment Complete; Topline Data Expected in Late 2Q2020

 

CONNECT - FX: A Pivotal Trial In FXS 15 • 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 • Capturing qualitative data on clinical relevance of FXS behaviors • New data presented at ISCTM (February 2020) and ASENT (March 2020) further validate core FXS behaviors from the perspective of caregivers • Top line results expected in late 2Q2020

 

CONNECT - FX Demographics 16 Patients n Randomization: Enrollment complete 212 Number of male patients 159 (75%) Mean age at randomization in study 9.7 years Completed 14 - week Tx period (as of 3/9/2020) 163 Percent of completed patients enrolling in CONNECT - FX OLE 97%

 

Baseline Behavior Severity: CONNECT - FX vs Ph2 FAB - C 17 Prospective inclusion criteria expected to provide a more severely impacted population which we believe should enhance ability to demonstrate a strong signal of activity and minimize response variability Note : Higher baseline scores denote more severe behaviors ABC - C FXS Subscale CONNECT - FX baseline score Phase 2 FAB - C baseline score Social Avoidance (12 point scale) 7.2 5.1 Irritability (54 point scale) 28.1 18.2 Socially Unresponsive / Lethargic (39 point scale) 13.2 8.7 Hyperactivity (30 point scale) 18.4 14.5 Stereotypy (18 point scale) 9.4 7.9 Inappropriate Speech (12 point scale) 6.9 6.1

 

CONNECT - FX 18 • W ith positive results in pivotal trial, Zynerba intends to request a meeting with the FDA to : • Determine acceptability of data as basis for NDA filing by YE 2020 • Seek advice on marketing authorization preparation • Potential approval by mid - year 2021 • Zynerba believes the indication may be the treatment of behavioral symptoms associated with FXS

 

19 • Presented data at SSBP* showing constellation of shared socio - behavioral symptoms in ASD, FXS, and 22q11.2DS • These include anxiety leading to: • Isolation and social avoidant behaviors • Irritability • Attention deficits • Poor communication Improvements in Behavior May Provide a Read - Through to Other Zygel Studies * Common Behavioral Features of Autism, Fragile X Syndrome, and 22q11.2 Deletion Syndrome , SSBP, 2019 ASD FXS 22q11.2DS Anxiety Social avoidance Seeks isolation Lack of interaction Attention deficits Poor attention Common behavioral Features of ASD, FXS, and 22q11.2DS* *Common Behavioral Features of Autism, Fragile X Syndrome , and 22q11.2 Deletion Syndrome , Society for the Study of Behavioural Phenotypes (SSBP), 2019

 

20 Autism Spectrum Disorder (ASD) in pediatric patients

 

ASD in Pediatrics Overview 21 • Near - rare disorder affecting ~ 1MM pediatric and adolescent pts • DSM - 5 diagnosis • Includes Autistic disorder, Asperger’s syndrome, and Pervasive Development Disorder - not otherwise specified (PDD - NOS) • Symptoms include • 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 • A ccelerating rate of diagnosis but only two FDA approved products • Both atypical antipsychotics have s ignificant side effect profile • Neither approved to address the key symptoms of social impairment and anxiety

 

Developing Zygel in ASD 22 • Newer studies suggest ASD is linked to disruption in the EC system • Altered anandamide signaling may contribute to ASD - related social and communication impairments • EC system modulates many cellular functions and molecular pathways altered in ASD: imbalanced GABAergic, glutamatergic transmission, oxidative stress, immune dysregulation and altered energy metabolism • Clinical and anecdotal data show improvement in social avoidance and anxiety in children with CBD • CBD may modulate the EC system and improve certain autism - related behaviors • Two recent US patents directed to methods of treating ASD by transdermally administering synthetic or purified cannabidiol , respectively, provide IP protection to 2038 • Enrollment complete in Phase 2 study in pediatric and adolescent patients with ASD • Top line results expected in 2Q2020

 

BRIGHT Phase 2 Trial in ASD 23 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 Target: 36 patients; 37 enrolled Four through 17 years of age Screening Zygel 14 Weeks Weight based dosing: 14 Weeks 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) • Clinical Global Impression – Severity (CGI - S) and Improvement (CGI - I ) Enrollment Complete ; Topline Data Expected in 2Q2020 24 Weeks Open label extension • Qualitative Caregiver Reported Behavioral Problems Survey • Autism Diagnostic Observation Schedule® (ADOS - 2): Baseline only • Children's Sleep Habits Questionnaire (CSHQ): Baseline and EOS (week 38) only E fficacy assessments (primary efficacy assessment = week 14 vs baseline ) :

 

Baseline Patient Demographics Demographic BRIGHT Patients N = 37 Age, years Mean (range ) 9.2 (3 - 16) Sex, n (%) Male Female 34 (91.9) 3 (8.1) Race, % White Aboriginal Asian Other 75.7 5.4 8.1 10.8 BRIGHT Trial Patient Demographics

 

25 Baseline Disease Characteristics ABC - C Irritability Subscale score (0 - 45) n Mean (range) 37 30.0 (18 - 43) ADOS® - 2 comparison score n Mean (range) <5 (mild ASD), n (%) 5 - 7 (moderate ASD), n (%) 8 - 10 (severe ASD), n (%) 36 7.5 (4 - 10) 2 (5.6) 19 (52.8) 15 (41.7) DSM - 5 severity level Level 1 (mild), n (%) Level 2 (moderate), n (%) Level 3 (severe), n (%) 3 (8.1) 15 (40.5) 19 (51.4) PRAS - ASD score ( 0 - 75; >52 suggests possible clinical anxiety) n Mean (range) >52, n (%) 37 40.9 (21 - 68) 9 (24.3) ADOS - 2: 94 % of patients have moderate to severe symptoms of ASD at baseline DSM - 5: 92% of patients have moderate to severe symptoms of ASD at baseline PRAS - ASD: 24 % of the enrolled patients had scores >52, indicating possible clinical anxiety BRIGHT Disease Characteristics Confirm a Moderate - to - Severe Population ABC - C Irritability subscale: Score of 30 provides confirmation of severity

 

22q11.2 Deletion Syndrome ( 22q) 26

 

22q Overview 27 • Most common contiguous gene deletion syndrome • Rare disorder: ~81K patients in US • Midline condition with abnormalities affecting palate, face, heart and other organs; surgically corrected in infancy • Neuropsychiatric illnesses (anxiety disorders, ASD) and learning disabilities common and impactful • 22q associated with increased anxiety, withdrawn behavior and social interaction problems • Early onset of neuropsychiatric symptoms disrupts development and QOL, and heightens risk of later psychotic disorders • 25 - fold increased risk of developing schizophrenia vs. 1% lifetime risk in general population

 

22q Patient Management 28 • Two primary stages of 22q patient management: • During infancy, doctors address acute physical concerns, such as anomalies of heart and palate, with surgery • Once the physical concerns are stabilized, focus shifts to managing neuropsychiatric symptoms, such as anxiety and autistic behaviors • No approved drugs indicated for 22q

 

Developing Zygel in 22q 29 • CBD may treat neuropsychiatric symptoms in 22q due to activity as: • Modulator of endocannabinoid system • Agonist at serotonin 1A receptors • Antagonist at GPR55 receptors • Early control of anxiety may delay the development of psychosis • Phase 2 study underway in pediatric and adolescent patients with 22q • Top line results now expected in 3Q2020

 

INSPIRE Phase 2 Trial in 22q 30 Target: 20 patients Six through 17 years of age Screening Zygel 14 Weeks Weight based dosing: 14 Weeks 250 mg to 500 mg daily E fficacy 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 CBD Gel) on P ediatr i c Behavio r al and E motional Symptoms of 22q11.2 Deletion Syndrome Enrollment Ongoing; Topline Data Expected in 2 3 Q2020 24 Weeks Open label extension

 

DEE Developmental and Epileptic Encephalopathies 31

 

DEE Patients are Medically Fragile 32 • G roup 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 • Many wheelchair bound with feeding tubes • Most common and debilitating seizure types in DEEs are: • Focal impaired - awareness seizures (FIAS) – formerly known as complex partial • Focal to bilateral tonic - clonic and generalized tonic - clonic seizures – commonly known as convulsive seizures (CS)

 

BELIEVE 1 Phase 2 Trial in DEE 33 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 Six months Zygel 250 mg to 1000 mg daily Completed; Reported Positive Topline Results on 9/18/19

 

34 BELIEVE 1: Clinically Meaningful Seizure Reductions from Baseline and Sustained through Six Months in DEE 0 10 20 30 40 50 60 70 Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Median Percent Reduction from Baseline, FIAS and CS N=33 N=33 N=33 N=32 N=32 N=29 16 44 44 47 58 51 0 10 20 30 40 50 60 70 Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 ≥50% Responder Rate, FIAS and CS N=33 N=33 N=33 N=32 N=32 N=29 30 42 46 47 63 55 Median Percent Reduction % of Pts with ≥50% Median Seizure Reduction % % % % % % % % % % % % % %

 

35 • All events in six month period, whether unrelated or related to study, drug are reported as adverse events (AEs) (e.g.: influenza, runny nose, ingrown toenail, scrapes, etc.) • AEs common in this medically fragile population, and expected in a six - month trial • As a result, most patients experienced an AE • Most were mild and transient • Only one patient discontinued due to an AE (application site reaction) • Low rate of serious adverse events (SAE ) • Only two SAEs deemed possibly drug - related (LRTI and status epilepticus) • No drug - related hepatic, gastrointestinal, or lethargy - related SAEs • Tolerability profile consistent with the safety database for Zygel • May compare favorably to tolerability profiles of reported safety data from oral CBD solution 1 and other currently available AEDs 2 BELIEVE 1 Safety Well Tolerated in this Six Month Trial 1 Devinsky - Lancet Neurol 2016 2 Moavero – Expert Opin D rug Saf , 2018

 

36 • Parents and caregivers provided qualitative assessment on their child’s overall experiences with Zygel • Improvements were seen in seizure intensity and duration , and socio - behavioral and cognitive impairments • Improvements in >25% of children: • 58 % reported improved vitality (e.g. alertness / awareness, energy) • 51% reported improvement in seizures • 47% reported improved cognition and concentration • 44% reported improved socially avoidant behaviors • 28% reported that their child attended school on time / more often • Improvements in socio - behavioral and cognitive impairments provide additional confidence in design of FXS, ASD and 22q11.2DS (22q) studies BELIEVE 1: Qualitative Assessments of Behavioral and Cognitive Improvements

 

37 • Efficacy results: • Clinically meaningful reductions in seizures beginning in month two and sustained through six months • Suggest improvements on important behavioral symptoms • Safety results: • Zygel was well tolerated • Consistent with previously reported Zygel studies • May compare favorably to tolerability profiles of reported safety data from oral CBD solution 1 and other currently available AEDs 2 • Zynerba approach to FDA approval will likely focus on most common and disabling seizure types in DEE, rather than patient syndromes Compelling Results Suggest a Pathway to Pivotal Trials Anticipate Meeting with FDA in 1H2020 1 Devinsky - Lancet Neurol 2016 2 Moavero – Expert Opin D rug Saf , 2018

 

38 Syndromes and encephalopathies Dravet LGS West Early myoclonioc epilepsy Hypoxic - ischemic e nceph . S eizure type Focal Impaired Awareness Bilateral Tonic Clonic Generalized Tonic Clonic Focal aware Absence Convulsive Other Seizure types Consciousness impairing seizures Doose Ohtahara Landau - Kleffner Other Syndromes CDKL5 enceph . Planned Approach to FDA All DEE Patients with Consciousness Impairing Seizures Zynerba Planned Approach

 

Financial Strength 39 • Clean balance sheet • No debt, 23.6M shares outstanding (as of March 4, 2020) • Cash and cash equivalent position of $70.1M as of December 31, 2019 • Cash runway expected to be sufficient to fund operations and capital requirements into the second half of 2021 • Beyond the expected NDA submission and potential approval in FXS

 

Expected Clinical Milestones in 2020 40 FXS DEE Report pivotal CONNECT - FX topline results ASD 22q 1Q 2020 2Q 2020 Report Ph. 2 BRIGHT topline results Report Ph. 2 INSPIRE topline results 3Q 2020 4Q 2020 Meet with FDA to Discuss DEE pivotal program NDA submission

 

Corporate Overview March 10, 2020