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): January 13, 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 8.01 Other Events

 

On January 13, 2020, Zynerba Pharmaceuticals, Inc. (the “Company”) issued a press release announcing the achievement of its enrollment target for the Company’s Phase 2 BRIGHT (An Open-Label Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Autism Spectrum Disorder) trial of Zygel for the treatment of pediatric and adolescent patients with autism spectrum disorder. A copy of this press release is attached hereto as Exhibit 99.1 and incorporated herein by reference.

 

On January 13, 2020 the Company also issued a press release announcing that enrollment is nearing completion in the Company’s pivotal CONNECT-FX (Clinical study of Cannabidiol (CBD) in Children and Adolescents with Fragile X) trial of Zygel in children and adolescents with Fragile X syndrome and providing updates regarding its product pipeline. A copy of this press release is attached hereto as Exhibit 99.2 and incorporated herein by reference.

 

On January 13, 2020, the Company posted on its website a slide presentation, which is attached as Exhibit 99.3 to this Current Report on Form 8-K and is incorporated herein by reference. Representatives of the Company will use the presentation in various meetings with investors, analysts and other parties from time to time.

 

Item 9.01 Financial Statements and Exhibits

 

The following exhibits are being filed herewith:

 

(d) Exhibits

 

Exhibit
No.
  Document
99.1   Press Release, dated January 13, 2020
99.2   Press Release, dated January 13, 2020
99.3   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: January 13, 2020

 

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

 

 

 

Exhibit 99.1

 

 

Zynerba Pharmaceuticals Announces Achievement of Enrollment Target in Phase 2 Trial of Zygel™ in Autism Spectrum Disorder

 

- Topline Results from BRIGHT Study Expected in the Second Quarter of 2020 -

 

DEVON, Pa., January 13, 2020 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced the achievement of its enrollment target for the 14-week Phase 2 BRIGHT (An Open-Label Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Autism Spectrum Disorder) trial of Zygel™ for the treatment of pediatric and adolescent patients with autism spectrum disorder (ASD). The Company expects to announce topline results from this study in the second quarter of 2020.

 

“We are committed to developing new treatment options to improve outcomes in patients suffering from a variety of neuropsychiatric conditions including autism spectrum disorder and achieving our enrollment target in the BRIGHT trial is an especially meaningful step toward this goal,” said Joseph M. Palumbo, MD, FAPA, MACPsych, Chief Medical Officer of Zynerba. “We would like to thank everyone involved in this study to date, particularly the participating patients and their caregivers, as well as the investigators. We look forward to announcing topline results from this study in the second quarter of 2020.”

 

The 14-week exploratory Phase 2 BRIGHT trial has enrolled 36 patients with ASD at a single clinical site in Australia. The trial is designed to evaluate the efficacy and safety of Zygel in children and adolescents (ages four through 17) with ASD as confirmed by DSM-5 diagnostic criteria for ASD. Enrolled patients are receiving weight-based initial doses of 250 mg daily or 500 mg daily of Zygel. The efficacy assessments include the Aberrant Behavior Checklist (ABC), Parent Rated Anxiety Scale – Autism Spectrum Disorder (PRAS-ASD), Autism Impact Measure (AIM), the Children’s Sleep Habit Questionnaire (CSHQ), and Clinical Global Impression – Severity and Improvement (CGI-S, CGI-I). After completing dosing in the 14-week period, participants may enroll in a six-month extension trial.

 

Using the Autism Diagnostic Observation Schedule (ADOS-2) which is administered at baseline by a qualified clinician, 94% of enrolled patients had moderate-to-severe symptoms of ASD at baseline. The mean baseline ABC-C Irritability subscale score of 30.0 further supports the severity of the enrolled patient population. Thirty-three (92%) are male. The mean age of these patients is 9.3 years.

 

About Autism Spectrum Disorder (ASD)

 

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

 

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About Zygel™

 

Zygel (cannabidiol [CBD] gel) is the first and only pharmaceutically-manufactured CBD formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that Fragile X syndrome (FXS) and other neuropsychiatric conditions including ASD may be associated with a disruption in the endocannabinoid (EC) system. Clinical and anecdotal data suggest that CBD may modulate the EC system and improve certain core social and behavioral autism-related symptoms, including social avoidance and anxiety.

 

Zygel is being studied in clinical trials in a number of rare and near-rare neuropsychiatric conditions. Target enrollment has been achieved in the Phase 2 BRIGHT trial of Zygel in ASD, with topline data anticipated in the second quarter of 2020. Enrollment is ongoing in CONNECT-FX, a multi-national, randomized, double blind, placebo-controlled pivotal clinical trial of Zygel in Fragile X syndrome (https://www.connectfxtrial.com/) and in the Phase 2 INSPIRE trial in 22q11.2 deletion syndrome. Zynerba also expects to meet with the U.S. Food and Drug Administration in the first half of 2020 to discuss the recently announced positive topline safety and efficacy data from its Phase 2 BELIEVE 1 clinical trial in patients with developmental and epileptic encephalopathies, and the clinical path forward.

 

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.  

 

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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. For example, there can be no guarantee that the Company will obtain approval for Zygel from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if Zygel is approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. 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 FDA 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; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

 

Zynerba Contact

 

William Roberts, Vice President, Investor Relations and Corporate Communications

Zynerba Pharmaceuticals

484.581.7489

robertsw@zynerba.com

 

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Exhibit 99.2

 

 

 

Zynerba Pharmaceuticals Announces that Enrollment is Nearing Completion in Pivotal CONNECT-FX Trial in Fragile X Syndrome

 

– Company Confirms Expectation of Topline Results in the Second Quarter of 2020 –

 

DEVON, Pa., January 13, 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 the pivotal CONNECT-FX (Clinical study of Cannabidiol (CBD) in Children and Adolescents with Fragile X) trial of Zygel™ in children and adolescents with Fragile X syndrome (FXS) in advance of this week’s investor meetings in San Francisco.

 

Enrollment is nearing completion in 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 in three through 17-year old patients with FXS. As of January 10, 2020, 178 patients of the 204 targeted for enrollment in the trial have been randomized into the trial. There are also 15 patients who have been screened but not yet randomized. The Company anticipates that screening for the trial will close near the end of January.

 

“We have made great progress throughout our pipeline in recent months,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We are nearing completion of enrollment in our pivotal CONNECT-FX study in patients with Fragile X syndrome, and we expect to report results from this trial late in the second quarter of 2020. We believe that the prospective inclusion criteria have enabled us to execute on a rigorous clinical trial of Zygel in a more severely impacted population of children and adolescents than included in our Phase 2 FAB-C study, which should enhance the study’s ability to demonstrate a strong signal of activity and minimize response variability. With key milestones expected from each of our clinical programs in the first half of this year, 2020 has the potential to be a compelling and exciting year.”

 

Baseline Data for Patients Randomized Through January 10, 2020

 

The primary endpoint for this trial 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 include 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 the Clinical Global Impression – Improvement scale (CGI-I) anchored to FXS behaviors evaluated at end of the treatment period. 

 

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As intended and prospectively designed, the trial has enrolled a more severely affected population than that enrolled in the previously completed Phase 2 FAB-C trial as measured by baseline behavioral symptoms, enabling the study to potentially demonstrate the anticipated full range of efficacy of Zygel in several behavioral domains. The ABC-CFXS mean baseline scores for patients randomized through January 10, 2020 in the CONNECT FX trial in comparison to the FAB-C trial are as follows (higher baseline scores denote more severe behaviors):

 

· Social Avoidance subscale (primary endpoint): 7.2 in CONNECT-FX vs 5.1 in FAB-C;

 

· Irritability subscale (key secondary endpoint): 28.1 in CONNECT-FX vs 18.2 in FAB-C;

 

· Socially Unresponsive/Lethargic subscale (key secondary endpoint): 13.2 in CONNECT-FX vs 8.7 in FAB-C;

 

· Hyperactivity subscale: 18.5 in CONNECT-FX vs 14.5 in FAB-C;

 

· Stereotypy subscale: 9.4 in CONNECT-FX vs 7.9 in FAB-C; and

 

· Inappropriate Speech subscale: 6.9 in CONNECT-FX vs 6.1 in FAB-C.

 

During screening, caregivers of patients in the trial are 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 in CONNECT-FX. To date, 96% of the 141 patients who have completed CONNECT-FX have enrolled in the open label extension trial.

 

Of the 178 patients randomized as of January 10, 2020, 135 (76%) are male and the mean age in the study is 9.6 years.

 

The Company expects to disclose topline results of this study late in the second quarter of 2020. If the results are positive, the Company expects to meet with the U.S. Food and Drug Administration (FDA) to determine acceptability of the data as a basis to submit its New Drug Application (NDA) for Zygel in FXS in the second half of 2020, with potential approval by mid-year 2021.

 

Other Corporate Updates

 

· As announced in a separate press release earlier this morning, the Company has achieved its enrollment target of 36 patients in the Phase 2 BRIGHT trial of Zygel for the treatment of pediatric and adolescent patients with autism spectrum disorder (ASD). Topline results are expected in the second quarter of 2020;

 

· Zynerba remains on track to report top line results from the Phase 2 INSPIRE study of Zygel in 22q11.2 deletion syndrome (22q) in the second quarter of 2020;

 

· The Company expects to meet with the FDA in the first half of 2020 to discuss the clinical path forward for Zygel in the treatment of developmental and epileptic encephalopathies (DEE);

 

· As of September 30, 2019 Zynerba had $77.5 million in cash and cash equivalent, which it believes is sufficient to fund its operations and capital requirements into the second half of 2021.

 

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About Zygel™

 

Zygel (CBD gel) is the first and only pharmaceutically-manufactured CBD formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that Fragile X syndrome (FXS) and other neuropsychiatric conditions including ASD may be associated with a disruption in the endocannabinoid (EC) system. Clinical and anecdotal data suggest that CBD may modulate the EC system and improve certain core social and behavioral autism-related symptoms, including social avoidance and anxiety.

 

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.  

 

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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. For example, there can be no guarantee that the Company will obtain approval for Zygel from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if Zygel is approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. 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 FDA 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; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

 

Zynerba Contact

 

William Roberts, Vice President, Investor Relations and Corporate Communications

Zynerba Pharmaceuticals

484.581.7489

robertsw@zynerba.com

 

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Exhibit 99.3

 

Corporate Overview January 2020

 

 

Forward - Looking Statements 2 © 20 20 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 • Approaching enrollment target in pivotal CONNECT - FX FXS trial • Achieved target enrollment in Phase 2 BRIGHT ASD study • 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 2Q2020 Topline Phase 2 data in 2Q2020 Topline Phase 2 data in 2Q2020 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 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

 

 

CONNECT - FX: A Pivotal Trial In FXS 13 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 Three through 17 years of age Screening Open label extension 14 weeks 12 months Enrollment Nearing Completion; Topline Data Expected in 2Q2020

 

 

CONNECT - FX: A Pivotal Trial In FXS 14 • 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 CGI - I (anchored to FXS behaviors) at end of treatment • Aligned with FDA’s ‘Voice of the Patient’ Guidance • Capturing qualitative data on clinical relevance of FXS behaviors • New data presented at SSBP (September 2019) further validate core FXS behaviors from the perspective of caregivers • Top line results expected in 2Q2020

 

 

CONNECT - FX Enrollment Status and Demographics 15 Patients n* Randomized (target =204) 178 Screened but not yet randomized 15 Completed 14 - week Tx period 141 Percent of completed patients enrolling in CONNECT - FX OLE 96% *As of January 10, 2020 Screening Expected to Complete by End of January 2020 Demographic data in 178 enrolled pts Number of male patients 135 (76%) Mean age in study 9.6 years

 

 

Baseline Behavior Severity: CONNECT - FX vs Ph2 FAB - C 16 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) 18.5 14.5 Stereotypy (18 point scale) 9.4 7.9 Inappropriate Speech (12 point scale) 6.9 6.1

 

 

CONNECT - FX 17 • 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

 

 

18 • 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

 

 

19 Autism Spectrum Disorder (ASD) in pediatric patients

 

 

ASD in Pediatrics Overview 20 • 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 21 • 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 • Recent US patent directed to methods of treating ASD with synthetic cannabidiol provides IP protection to 2038 • Target enrollment achieved in Phase 2 study in pediatric and adolescent patients with ASD • Top line results expected in 2Q2020

 

 

BRIGHT Phase 2 Trial in ASD 22 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 Four through 17 years of age Screening Zygel 14 Weeks Weight based dosing: 14 Weeks 250 mg to 500 mg daily Follow up assessments Week 16 / 17 E fficacy assessments (week 14 vs baseline) include: • Aberrant Behavior Checklist • Parent Rated Anxiety Scale – Autism Spectrum Disorder • Autism Impact Measure • Clinical Global Impression – Severity and Improvement Target Enrollment Achieved; Topline Data Expected in 2Q2020

 

 

BRIGHT Trial Patient Demographics 23 36 patients enrolled in the BRIGHT trial: • 94% of patients have moderate to severe symptoms of ASD at baseline as measured by the Autism Diagnostic Observation Schedule (ADOS - 2) • Mean baseline ABC - C Irritability subscale: 30.0 • 33 (92%) are male • Mean age: 9.3 years

 

 

22q11.2 Deletion Syndrome ( 22q) 24

 

 

22q Overview 25 • 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 26 • 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 27 • 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 expected in 2Q 2020

 

 

INSPIRE Phase 2 Trial in 22q 28 Target: 20 patients Six through 17 years of age Screening Zygel 14 Weeks Weight based dosing: 14 Weeks 250 mg to 500 mg daily Follow up assessments Week 16 / 17 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 2Q2020

 

 

DEE Developmental and Epileptic Encephalopathies 29

 

 

DEE Patients are Medically Fragile 30 • 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 31 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

 

 

32 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 % % % % % % % % % % % % % %

 

 

33 • 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

 

 

34 • 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

 

 

35 • 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

 

 

36 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 37 • Clean balance sheet • No debt, 23.2M shares outstanding (as of November 1, 2019) • Cash and cash equivalent position of $77.5M as of September 30, 2019 • Cash 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 38 FXS DEE Report pivotal CONNECT - FX topline results ASD 22q 1Q 2Q Report Ph. 2 BRIGHT topline results Report Ph. 2 INSPIRE topline results 3Q 4Q Meet with FDA to discuss DEE pivotal program NDA submission

 

 

Corporate Overview January 2020