Category: Recent News

Zygel™ (ZYN002) achieved statistically significant and clinically meaningful improvements from baseline in multiple efficacy assessments and was generally well-tolerated through 38 weeks of treatment in INSPIRE, a Phase 2 trial with Zygel in children and adolescents with 22q11.2 deletion syndrome (22q)

Devon, PA, September 14, 2023 – Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, announces an oral presentation at The Society for the Study of Behavioural Phenotypes (SSBP) 25^th International Research Symposium, being held virtually September 14-15, 2023. Helen (Honey) Heussler, MBBS FRACP, DM, Associate Professor, Faculty of Medicine, Child Health Research Centre, University of Queensland, Australia, will present data from the open-label Phase 2 INSPIRE trial. A copy of the presentation will be available on the Zynerba corporate website at www.zynerba.com/publications.

The presentation titled, “An Open-label Trial Assessing Short- and Long-term Tolerability and Efficacy of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE),” includes data demonstrating that through 38-weeks of treatment, statistically significant improvements (p<0.05) were seen in children and adolescents treated with Zygel in the Pediatric Anxiety Rating Scale (PARS-R), all five scales of the Anxiety, Depression and Mood Scale (ADAMS), and all five subscales of the Aberrant Behavior Checklist – Community (ABC-C). These results are consistent with the previously reported 14-week treatment data suggesting a positive risk-benefit profile for Zygel in improving anxiety-related and other behavioral symptoms in children and adolescents with 22q when added to standard of care. In addition, caregivers for patients in the study reported improvement in the most impactful self-identified behavioral, emotional or social problems during the 38-week treatment period. Zygel was shown to be generally well tolerated, and the safety profile was consistent with previously released data from other Zygel clinical trials. Three patients reported treatment related adverse events which were all mild in severity and application site related. One patient discontinued treatment due to adverse events not related to Zygel.

“Anxiety and behavioral symptoms have significant impact on the lives of individuals with 22q, and these findings are encouraging and warrant further study of Zygel in a controlled trial to confirm these results,” said Professor Heussler.

About Zygel

Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide consistent drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS) and 22q11.2 deletion syndrome (22q). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

 

About Zynerba Pharmaceuticals, Inc.

Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

 

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation, banking stability or global instability, including political instability, may disrupt our business operations or our financial condition. 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 Contacts

Peter Vozzo

ICR Westwicke

Office: 443.213.0505

Cell: 443.377.4767

Peter.Vozzo@Westwicke.com

 

 

 

Innovative potential new therapeutic option for rare/orphan neuropsychiatric disorders with high unmet medical needs

Lead asset in pivotal Phase 3 trial for Fragile X syndrome and has completed Phase 2 proof-of-concept study in 22q11.2 deletion syndrome

Conference call and webcast to be held today at 8:30 AM ET

Plymouth Meeting, PA, and Devon, Pa, August 14, 2023 — Harmony Biosciences Holdings, Inc. (“Harmony”) (Nasdaq: HRMY), a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases, today announced a definitive agreement to acquire Zynerba Pharmaceuticals, Inc. (“Zynerba”) (Nasdaq: ZYNE), a leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, including Fragile X syndrome (FXS).

Under the terms of the definitive agreement, Harmony will commence a tender offer to acquire all outstanding shares of Zynerba for a purchase price of $1.1059 per share in cash, or $60 million in the aggregate, plus one non-tradeable contingent value right (CVR) per share, representing the right to receive potential additional payments of up to $140 million in the aggregate, subject to the achievement of certain clinical, regulatory and sales milestones, as described in more detail below.

“This is an important step in Harmony’s strategy to build a diversified portfolio of innovative assets to address unmet medical needs and drive our long-term growth. This acquisition affords us the opportunity to advance the development and delivery of a potentially transformative treatment for the symptoms of Fragile X syndrome and other rare neuropsychiatric disorders,” said Jeffrey M. Dayno, M.D., President and Chief Executive Officer at Harmony Biosciences. “In addition to the strength of our core business in narcolepsy and our current life cycle management programs, led by idiopathic hypersomnia, we are excited to continue to diversify our portfolio beyond sleep/wake by adding Zynerba’s clinical development programs to our pipeline. The team at Zynerba has been dedicated to these programs and we are confident that our combined efforts could have a profound impact on individuals living with rare neuropsychiatric disorders and their families.”

“Harmony’s development and commercial expertise, technologies, people and focus on rare neurological diseases are an excellent strategic fit with Zynerba,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “I am very proud of Zynerba’s accomplishments with Zygel™ to date. With Harmony’s scale, resources and proven commercial excellence, they are well positioned to potentially bring to market the first pharmaceutical product indicated for the treatment of behavioral symptoms of Fragile X syndrome and to maximize the value of Zygel.”

Zynerba’s lead asset, Zygel, is the first and only pharmaceutically manufactured, synthetic cannabidiol, a non-euphoric cannabinoid, formulated as a patent-protected permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. Zygel is manufactured through a synthetic process in a cGMP facility and is not extracted from the cannabis plant. Therefore, it is devoid of THC, which is what causes the euphoric effect of cannabis, and has the potential to be a nonscheduled product if approved. Zygel is currently being evaluated in a pivotal Phase 3 clinical trial for patients living with FXS, known as the RECONNECT Trial. Additionally, Zygel showed positive signals in an open label Phase 2 trial in patients living with 22q11.2 deletion syndrome (22q), called the INSPIRE Trial.

Cannabidiol, the active ingredient in Zygel, has been granted orphan drug designation by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of FXS and for the treatment of 22q. Additionally, Zygel has received FDA Fast Track designation for the treatment of behavioral symptoms in patients with FXS.

FXS is a rare genetic disorder that affects approximately 80,000 people in the U.S., causing intellectual disabilities and behavioral challenges. Despite considerable progress in medical science, there remains a significant unmet medical need in treating patients living with this debilitating disorder. There are currently no FDA approved therapies to treat FXS.

It is estimated that there are approximately 80,000 people living with 22q in the U.S. Patients with 22q are affected by symptoms related to many organ systems including neuropsychiatric symptoms such as anxiety and behavioral difficulties. There are currently no FDA-approved therapies to treat 22q.

Transaction Details

Under the terms of the definitive agreement, which was unanimously approved by the boards of directors of Harmony and Zynerba, Harmony will commence a tender offer to acquire all outstanding shares of Zynerba for a purchase price of $1.1059 in cash per share, or $60 million in the aggregate payable at closing of the transaction plus one non-tradeable CVR representing the right to receive potential additional payments of up to $140 million or approximately $2.5444 in additional cash per share, for a total potential consideration of up to $200 million in cash. The CVR is payable subject to certain terms and conditions upon achievement of the following milestones:

Clinical Milestones

• Completion of FXS Phase 3 clinical trial: $15 million in the aggregate or approximately $0.2747 per share
• Positive data readout from FXS Phase 3 clinical trial:

$30 million in the aggregate or approximately $ 0.5494 per share if completed on or before December 31, 2024

$20 million in the aggregate or approximately $ 0.3663 per share if completed on or before June 30, 2025

$10 million in the aggregate or approximately $ 0.1831 per share if completed after June 30, 2025

Regulatory Milestones

• FDA approval in FXS: $35 million in the aggregate or approximately $0.6389 per share
• FDA approval in Second Indication: $15 million in the aggregate or approximately $0.2707 per share

Net Sales Milestones

• Achievement of $250 million in aggregate Net Sales: $15 million in the aggregate or approximately $0.2702 per share
• Achievement of $500 million in aggregate Net Sales: $30 million in the aggregate or approximately $0.5405 per share

Each CVR is subject to the achievement of the milestone conditions described above, and there can be no assurance whether any such milestones will be achieved or when any payments will be made with respect to any CVR.

Harmony will fund the transaction from its existing cash on hand. As of June 30, 2023, Harmony had cash, cash equivalents and investment securities of $429.6 million. Zynerba’s existing cash and cash equivalent balance was approximately $36.0 million as of June 30, 2023.

The transaction is expected to close by the fourth quarter of 2023, subject to customary closing conditions, including that the holders of at least a majority of the outstanding shares of Zynerba’s common stock tender such shares to Harmony in connection with the tender offer. Following the successful closing of the tender offer, Harmony will acquire any shares of Zynerba it does not already own through a second-step merger at the same per share offer price as paid in the tender offer. Zynerba’s board of directors unanimously recommends that Zynerba’s stockholders tender their shares in the tender offer.

Advisors

For Harmony, Hogan Lovells US LLP is acting as legal counsel. For Zynerba, MTS Health Partners, L.P. is acting as financial advisor and Goodwin Procter LLP is acting as legal counsel.

Conference Call Today at 8:30 AM ET

At 8:30 AM ET Harmony will host a live webcast to review this proposed acquisition. The live and replay webcast of the call will be available on the investor relations page of our website at https://ir.harmonybiosciences.com/. To participate in the live call by phone, dial (800) 245-3047 (domestic) or +1 (203) 518-9765 (international), and reference passcode HRMY0814.

About Harmony Biosciences

At Harmony Biosciences, we specialize in developing and delivering treatments for rare neurological diseases that others often overlook. We believe that where empathy and innovation meet, a better life can begin for people living with neurological diseases. Established by Paragon Biosciences, LLC, in 2017 and headquartered in Plymouth Meeting, PA, our team of experts from a wide variety of disciplines and experiences is driven by our shared conviction that innovative science translates into therapeutic possibilities for our patients, who are at the heart of everything we do. For more information, please visit www.harmonybiosciences.com.

About Zynerba Pharmaceuticals, Inc.

Zynerba Pharmaceuticals is the leader in innovative pharmaceutically produced, synthetic transdermal cannabidiol therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com.

About Fragile X Syndrome

Fragile X syndrome (FXS) is a rare genetic disorder that is the leading known cause of both inherited intellectual disability and autism spectrum disorder, affecting 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females. The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. There are approximately 80,000 people in the U.S. and approximately 121,000 people in the European Union and UK living with FXS. There is a significant unmet medical need in patients living with FXS as there are currently no FDA approved treatments for this disorder.

FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including the endocannabinoid system, and most critically, codes for a protein called FMRP. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat, resulting in deficiency or lack of FMRP. FMRP helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. In people with full mutation of the FMR1 gene, the CGG segment is repeated more than 200 times, and in most cases causes the gene to not function. Methylation of the FMR1 gene also plays a role in determining functionality of the gene. In approximately 60% of patients with FXS, who have complete methylation of the FMR1 gene, no FMRP is produced, resulting in dysregulation of the systems modulated by FMRP.

About 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome (22q) is a disorder caused by a small missing piece of the 22^nd chromosome. The deletion occurs near the middle of the chromosome at a location designated q11.2. It is considered a mid-line condition, with physical symptoms including characteristic palate abnormalities, heart defects, immune dysfunction, and esophageal / GI issues, as well as debilitating neuropsychiatric and behavioral symptoms, including anxiety, social withdrawal, ADHD, cognitive impairment and autism spectrum disorder. It is estimated that 22q occurs in one in 4,000 live births, suggesting that there are approximately 80,000 people living with 22q in the U.S. and 129,000 in the European Union and the UK. Patients with 22q deletion syndrome are managed by multidisciplinary care providers, and there are currently no FDA approved treatments for this disorder.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements. These forward-looking statements, including as they relate to Harmony and Zynerba, the anticipated occurrence, manner and timing of the proposed transaction, the future development of their technologies and product candidates, including the development of and market opportunities for Zynerba’s technology and product candidates, the future value (if any) of the contingent value rights, Harmony’s strategy, and the anticipated synergies and benefits from the proposed transaction, are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Potential risks, uncertainties and other factors to be considered include, among others, that Zynerba stockholders may not tender a sufficient number of shares in the tender offer; the length of time necessary to consummate the proposed transaction may be longer than anticipated, or it may not be consummated at all; problems may arise in successfully integrating the business and technologies of Harmony and Zynerba, and Harmony may not realize the expected benefits of the proposed transaction; the proposed transaction may involve unexpected costs; the businesses may suffer as a result of uncertainty surrounding the proposed transaction, including difficulties in maintaining relationships with third parties or retaining key employees; and even if the transaction is consummated no contingent consideration may become payable. For further discussion of these and other risks and uncertainties, see Harmony’s and Zynerba’s most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission (the “SEC”), including under the headings “Risk Factors.” You are cautioned to not place undue reliance on forward-looking statements, which speak only as of the date of this document. Except as required by law, neither Harmony nor Zynerba is under any duty to update any of the information in this document.

Additional Information about the Acquisition and Where to Find It:

In connection with the proposed acquisition, Harmony will commence a tender offer for the outstanding shares of Zynerba. The tender offer has not yet commenced. This document is for informational purposes only and is neither an offer to purchase nor a solicitation of an offer to sell shares of Zynerba, nor is it a substitute for the tender offer materials that Harmony and Xylophone Acquisition Corp (“Purchaser”) will file with the SEC upon commencement of the tender offer. At the time the tender offer is commenced, Harmony and Purchaser will file tender offer materials on Schedule TO, and Zynerba will file a Solicitation/Recommendation Statement on Schedule 14D-9 with the SEC with respect to the tender offer. Holders of shares of Zynerba common stock are urged to read the tender offer materials (including an Offer to Purchase, a related Letter of Transmittal and certain other tender offer documents) and the Solicitation/Recommendation Statement when they become available (as each may be amended or supplemented from time to time) because they will contain important information that holders of shares of Zynerba common stock should consider before making any decision regarding tendering their shares. The Offer to Purchase, the related Letter of Transmittal and certain other tender offer documents, as well as the Solicitation/Recommendation Statement, will be made available to all holders of shares of Zynerba at no expense to them. The tender offer materials and the Solicitation/Recommendation Statement will be made available for free at the SEC’s website at www.sec.gov. In addition, these materials will be available at no charge on the Enhanced SEC Filings section of the Investor Relations page of Zynerba’s website at https://www.zynerba.com/ and by directing a request to the information agent for the tender offer, whose information will be set forth in the Offer to Purchase.

 

Harmony Biosciences Contacts:

Investor:

Luis Sanay, CFA

445-235-8386
lsanay@harmonybiosciences.com

 

Media:

Cate McCanless

202-641-6086

cmccanless@harmonybiosciences.com

 

Zynerba Pharmaceuticals Contact:

Peter Vozzo

ICR Westwicke

443-213-0505

Peter.Vozzo@westwicke.com

 

Annual Meeting to Reconvene on August 25, 2023 at 9:00 a.m. EDT

Devon, PA, August 8, 2023 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE) (the “Company”), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that the new date for the adjourned 2023 Annual Meeting of Stockholders (“Annual Meeting”) is August 25, 2023 at 9:00 a.m. EDT in order to provide stockholders additional time to consider and vote on Proposal 2 to amend the Sixth Amended and Restated Certificate of Incorporation of the Company to effect a reverse stock split of the Company’s outstanding shares of common stock by a ratio of any whole number between 1-for-2 and 1-for-50, at any time prior to November 1, 2023, the implementation and timing of which shall be subject to the discretion of the Board of Directors of the Company. The August 25, 2023 meeting date replaces the previously announced August 11, 2023 date for the reconvened meeting and will be a “virtual” meeting of stockholders. The record date for the adjourned Annual Meeting continues to be April 17, 2023.

A stockholder may use one of the following simple methods to vote:

Vote by Internet at www.voteproxy.com until 11:59 PM EDT on August 24, 2023 using the control number appearing on the proxy card.

Vote by telephone by calling the toll-free telephone number 1-800-776-9437 until 11:59 PM EDT on August 24, 2023 using their control number appearing on the proxy card.

Vote by mail by marking, dating and signing the proxy card, and returning it in the postage-paid envelope provided to American Stock Transfer & Trust Company, LLC.

Vote at the virtual Annual Meeting by joining the meeting at https://web.lumiagm.com/236626312 (password: zyne2023) using the control number included on the proxy card.

Proxies previously submitted with respect to Proposal 2 will be voted at the reconvened Annual Meeting unless properly revoked; stockholders who have previously submitted their proxy or otherwise voted with respect to Proposal 2 and who do not want to change their vote need not take any action.

Details of the reverse stock split are included in the Company’s Proxy Statement for the Annual Meeting. The primary objective of implementing a reverse split is to satisfy the minimum bid price requirement for continued listing on the Nasdaq Capital Market. The Company’s Board believes that effecting the reverse split would increase the price of our common stock which would, among other things, help the Company to meet certain continued listing requirements of the Nasdaq Capital Market, appeal to a broader range of investors to generate interest in the Company, and improve perception of the Company’s common stock as an investment security.

If stockholders have any questions or need assistance with processing their vote, please contact the Company’s proxy solicitor, MacKenzie Partners, Inc. (email: proxy@mackenziepartners.com, or toll free: 1-800-322-2885).

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. 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 Contacts
Peter Vozzo
ICR Westwicke
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

Annual Meeting to Reconvene on August 11, 2023 at 9:00 a.m. EDT

Devon, PA, July 25, 2023 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE) (the “Company”), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that the new date for the adjourned 2023 Annual Meeting of Stockholders (“Annual Meeting”) is August 11, 2023 at 9:00 a.m. EDT in order to provide stockholders additional time to consider and vote on Proposal 2 to amend the Sixth Amended and Restated Certificate of Incorporation of the Company to effect a reverse stock split of the Company’s outstanding shares of common stock by a ratio of any whole number between 1-for-2 and 1-for-50, at any time prior to November 1, 2023, the implementation and timing of which shall be subject to the discretion of the Board of Directors of the Company. The August 11, 2023 meeting date replaces the previously announced July 27, 2023 date for the reconvened meeting and will be a “virtual” meeting of stockholders. The record date for the adjourned Annual Meeting continues to be April 17, 2023.

A stockholder may use one of the following simple methods to vote:

Vote by Internet at www.voteproxy.com until 11:59 PM EDT on August 10, 2023 using the control number appearing on the proxy card.

Vote by telephone by calling the toll-free telephone number 1-800-776-9437 until 11:59 PM EDT on August 10, 2023 using their control number appearing on the proxy card.

Vote by mail by marking, dating and signing the proxy card, and returning it in the postage-paid envelope provided to American Stock Transfer & Trust Company, LLC.

Vote at the virtual Annual Meeting by joining the meeting at https://web.lumiagm.com/236626312 (password: zyne2023) using the control number included on the proxy card.

Proxies previously submitted with respect to Proposal 2 will be voted at the reconvened Annual Meeting unless properly revoked; stockholders who have previously submitted their proxy or otherwise voted with respect to Proposal 2 and who do not want to change their vote need not take any action.

Details of the reverse stock split are included in the Company’s Proxy Statement for the Annual Meeting. The primary objective of implementing a reverse split is to satisfy the minimum bid price requirement for continued listing on the Nasdaq Capital Market. The Company’s Board believes that effecting the reverse split would increase the price of our common stock which would, among other things, help the Company to meet certain continued listing requirements of the Nasdaq Capital Market, appeal to a broader range of investors to generate interest in the Company, and improve perception of the Company’s common stock as an investment security.

If stockholders have any questions or need assistance with processing their vote, please contact the Company’s proxy solicitor, MacKenzie Partners, Inc. (email: proxy@mackenziepartners.com, or toll free: 1-800-322-2885).

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.
  
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. 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 Contacts
Peter Vozzo
ICR Westwicke
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

 

Annual Meeting Reconvened and Adjourned Without Conducting Business

Meeting to Reconvene on July 27, 2023 at 9:00 am EDT

Devon, PA June 28, 2023 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE) (the “Company”), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that the adjourned 2023 Annual Meeting of Stockholders (“Annual Meeting”) was reconvened and then adjourned, without conducting any business, in order to provide stockholders additional time to consider and vote on Proposal 2 to amend the Sixth Amended and Restated Certificate of Incorporation of the Company to effect a reverse stock split of the Company’s outstanding shares of common stock by a ratio of any whole number between 1-for-2 and 1-for-50, at any time prior to November 1, 2023, the implementation and timing of which shall be subject to the discretion of the Board of Directors of the Company.

The Company believes there is significant support for Proposal 2. At the time of the reconvened Annual Meeting approximately 46.9% of the outstanding shares entitled to vote had voted in favor of Proposal 2; however, because Proposal 2 must be approved by a majority of the outstanding shares entitled to vote, it has not yet received a sufficient number of votes in its favor. The Company’s Board of Directors continues to believe that Proposal 2 is advisable and that it is in the best interests of the Company’s stockholders to consider and act upon Proposal 2.

The Annual Meeting will be reconvened on July 27, 2023 at 9:00 am EDT, and will be a “virtual” meeting of stockholders. The record date for the adjourned Annual Meeting continues to be April 17, 2023. A stockholder may use one of the following simple methods to vote:

Vote by Internet at www.voteproxy.com until 11:59 PM EDT on July 26, 2023 using the control number appearing on the proxy card.

Vote by telephone by calling the toll-free telephone number 1-800-776-9437 until 11:59 PM EDT on July 26, 2023 using their control number appearing on the proxy card.

Vote by mail by marking, dating and signing the proxy card, and returning it in the postage-paid envelope provided to American Stock Transfer & Trust Company, LLC.

Vote at the virtual Annual Meeting by joining the meeting at https://web.lumiagm.com/236626312 (password: zyne2023) using the control number included on the proxy card.

Proxies previously submitted with respect to Proposal 2 will be voted at the reconvened Annual Meeting unless properly revoked; stockholders who have previously submitted their proxy or otherwise voted with respect to Proposal 2 and who do not want to change their vote need not take any action.

Details of the reverse stock split are included in the Company’s Proxy Statement for the Annual Meeting. The primary objective of implementing a reverse split is to satisfy the minimum bid price requirement for continued listing on the Nasdaq Capital Market. The Company’s Board believes that effecting the reverse split would increase the price of our common stock which would, among other things, help the Company to meet certain continued listing requirements of the Nasdaq Capital Market, appeal to a broader range of investors to generate interest in the Company, and improve perception of the Company’s common stock as an investment security.

If stockholders have any questions or need assistance with processing their vote, please contact the Company’s proxy solicitor, MacKenzie Partners, Inc. (email: proxy@mackenziepartners.com, or toll free: 1-800-322-2885).

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. 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 Contacts
Peter Vozzo
ICR Westwicke
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

Devon, PA, June 20, 2023 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that Armando Anido, Chairman and Chief Executive Officer of Zynerba, will present at the H.C. Wainwright 4th Annual Neuropsychiatry Virtual Conference being held June 26, 2023.

Investors interested in arranging a virtual meeting with the Company’s management during the conference should contact the H.C. Wainwright conference coordinator. A webcast of the presentation will be available on-demand here and under the Events & Webcasts tab of the Investors section of the Zynerba website at www.zynerba.com beginning June 26, 2023 at 7:00 a.m. ET. An archived replay will be available on the Company’s website following the event for 60 days.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the Company’s ability to regain compliance with the requirements for continued listing on the Nasdaq Capital Market, including the risk of not obtaining stockholder approval for a potential reverse stock split; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation, banking stability or global instability, including political instability, may disrupt our business operations or our financial condition. 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 Contacts
|Peter Vozzo
ICR Westwicke
Office: 443.213.0505
Peter.Vozzo@Westwicke.com

Meeting adjourned with respect to Proposal 2, Reverse Stock Split; Company encourages additional stockholders of record to vote before reconvened meeting on June 28, 2023

All other proposals approved

Devon, PA, June 13, 2023 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE) (the “Company”), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced that it has adjourned its 2023 Annual Meeting of Stockholders (“Annual Meeting”) solely with respect to Proposal 2 set forth in its Definitive Proxy Statement (“Proxy Statement”) filed with the Securities and Exchange Commission on April 21, 2023. All other proposals on the Proxy Statement were approved by stockholders during the Annual Meeting held earlier today.

Proposal 2 is a proposal to amend the Sixth Amended and Restated Certificate of Incorporation of the Company to effect a reverse stock split of the Company’s outstanding shares of common stock by a ratio of any whole number between 1-for-2 and 1-for-50, at any time prior to November 1, 2023, the implementation and timing of which shall be subject to the discretion of the Board of Directors of the Company. The Company has adjourned the Annual Meeting with respect to Proposal 2 to provide its stockholders additional time to vote on the proposal. Proposal 2 requires that a majority of the outstanding shares entitled to vote must vote “For” the proposal in order to pass. Based on the preliminary vote totals, 45.02% of the outstanding shares entitled to vote have voted For Proposal 2.

The Annual Meeting will resume with respect to Proposal 2 at 9:00 AM EDT on June 28, 2023. The reconvened Annual Meeting will also be a “virtual” meeting of stockholders. The record date for the Annual Meeting continues to be April 17, 2023. A stockholder may use one of the following simple methods to vote:

• Vote by Internet at www.voteproxy.com until 11:59 PM EDT on June 27, 2023 using the control number appearing on the proxy card.
• Vote by telephone by calling the toll-free telephone number 1-800-776-9437 until 11:59 PM EDT on June 27, 2023 using their control number appearing on the proxy card.
• Vote by mail by marking, dating and signing the proxy card, and returning it in the postage-paid envelope provided to American Stock Transfer & Trust Company, LLC.
• Vote at the virtual Annual Meeting by joining the meeting at https://web.lumiagm.com/236626312 (password: zyne2023) using the control number included on the proxy card.

Proxies previously submitted with respect to Proposal 2 will be voted at the reconvened Annual Meeting unless properly revoked; stockholders who have previously submitted their proxy or otherwise voted with respect to Proposal 2 and who do not want to change their vote need not take any action.

Details of the reverse stock split are included in the Company’s Proxy Statement for the Annual Meeting. The primary objective of implementing a reverse split is to satisfy the minimum bid price requirement for continued listing on the Nasdaq Capital Market. The Company’s Board believes that effecting the reverse split would increase the price of our common stock which would, among other things, help the Company to:

• Meet certain continued listing requirements of the Nasdaq Capital Market;
• Appeal to a broader range of investors to generate interest in the Company; and
• Improve perception of the Company’s common stock as an investment security.

If stockholders have any questions or need assistance with processing their vote, please contact the Company’s proxy solicitor, MacKenzie Partners, Inc. (email: proxy@mackenziepartners.com, or toll free: 1-800-322-2885).  

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. 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 Contacts
Peter Vozzo
ICR Westwicke
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com

Devon, PA, May 23, 2023 — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today announced an oral podium presentation and poster presentations at the American Society of Clinical Psychopharmacology Annual Meeting (ASCP 2023), being held May 30 – June 2, 2023, in Miami, Fla. Copies of the presentations will be made available on the Zynerba corporate website following the presentations at http://zynerba.com/publications/.

Oral Podium Presentation Details

Title:	An Open-Label Trial Assessing Short- And Long-Term Tolerability and Efficacy of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE) and Long-Term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome (ZYN2-CL-017)
Date:	Tuesday, May 30, 2023
Session:	Pharmaceutical Pipeline Session
Time:	3:20 p.m. – 3:30 p.m. ET
Location:	Salon 3 – The Loews Miami Beach

Poster Presentation Details

Title:	An Open-Label Trial Assessing Short- and Long-Term Tolerability and Efficacy of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE) [W49]
Title:	Long-term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome (ZYN2-CL-017) [W50]
Session:	Poster Session I
Date:	Wednesday, May 31, 2023
Time:	11:15 a.m. – 1:00 p.m. ET
Location:	Salon 4 – The Loews Miami Beach

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the Company’s ability to regain compliance with the requirements for continued listing on the Nasdaq Capital Market, including the risk of not obtaining stockholder approval for a potential reverse stock split; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation, banking stability or global instability, including political instability, may disrupt our business operations or our financial condition. 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 Contacts
Peter Vozzo
ICR Westwicke
Office: 443.213.0505
Peter.Vozzo@Westwicke.com

Enrollment continues in RECONNECT, a confirmatory pivotal Phase 3 trial of Zygel™ in patients with Fragile X syndrome; topline results expected first-half 2024

$44.4 million in cash and cash equivalents at March 31, 2023; Cash runway to mid-year 2024

Proposal for a reverse stock split is on the agenda for June 13, 2023 annual meeting of stockholders to satisfy the minimum bid price requirement for continued listing on the Nasdaq Capital Market

Devon, PA, May 15, 2023 —  Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, today reported financial results for the first quarter ended March 31, 2023, and provided an overview of recent operational highlights and a pipeline update.

“The first quarter of 2023 was a period of continued focus and execution on our two lead programs with Zygel,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “During the quarter we continued to enroll patients in our confirmatory pivotal Phase 3 RECONNECT trial as we are committed to bringing the first pharmaceutical product indicated for the treatment of behavioral symptoms of Fragile X syndrome to market. In addition, we expect continued dialogue with the U.S. Food and Drug Administration (FDA) in 2023 regarding an acceptable trial design for our Phase 3 program in patients with 22q deletion syndrome, with the goal of finalizing a trial design by the end of 2023.”

Operational Highlights and Pipeline Update

Zygel in Fragile X Syndrome (FXS)

• The Company expects topline results from RECONNECT, a confirmatory pivotal Phase 3 trial of Zygel in patients with FXS, in the first half of 2024. The Company believes that the results from RECONNECT, if positive, will be sufficient to support the submission of a New Drug Application (NDA) in the U.S. and a Marketing Authorization Application (MAA) in Europe for Zygel in patients with FXS.
• The Company presented data at the 55^th Gatlinburg Conference in April 2023 demonstrating that in the ongoing long-term safety and efficacy trial of Zygel in children and adolescents with FXS, Zygel was well-tolerated with long-term administration with up to 45 months of exposure. Patients with complete methylation, who match the primary efficacy population in the ongoing confirmatory trial, RECONNECT, achieved and maintained clinically meaningful changes in Social Avoidance over 24 months, further supporting this design enhancement for RECONNECT. (Press Release)

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

• As previously disclosed, based on the positive Phase 2 INSPIRE trial data announced in June 2022 (Press Release), the Company held an initial meeting with the FDA in the fourth quarter of 2022 to obtain feedback on the Phase 2 data and regulatory pathway for Zygel in patients with 22q. The Company expects to continue its productive dialogue with the FDA on this topic and arrive at an acceptable trial design by the end of 2023. The Company currently plans to initiate a Phase 3 program in children and adolescents with 22q following topline results from RECONNECT.
• The Company presented data at the 55^th Gatlinburg Conference in April 2023 that showed through 38-weeks of treatment, statistically significant improvements were seen in children and adolescents treated with Zygel in the Pediatric Anxiety Rating Scale (PARS-R), all five scales of the Anxiety, Depression and Mood Scale (ADAMS), and all five subscales of the Aberrant Behavior Checklist – Community (ABC-C). These results are consistent with the previously reported 14-week treatment data suggesting a positive risk-benefit profile for Zygel in improving anxiety-related and other behavioral symptoms in children and adolescents with 22q when added to standard of care. (Press Release).

Corporate – Reverse Stock Split

• Zynerba intends to seek approval of a reverse stock split at its Annual Meeting of Stockholders in June (Annual Meeting), which it would effect any time prior to November 1, 2023. Details of the reverse stock split are included in the Company’s Proxy Statement for the Annual Meeting. The primary objective of implementing a reverse split is to satisfy the minimum bid price requirement for continued listing on the Nasdaq Capital Market. The Company’s Board believes that effecting the reverse split would increase the price of our common stock which would, among other things, help the Company to:
  • Meet certain continued listing requirements of the Nasdaq Capital Market;
  • Appeal to a broader range of investors to generate interest in the Company; and
  • Improve perception of the Company’s common stock as an investment security.

Stockholders of record are encouraged to review the proxy materials filed with the SEC before voting. If stockholders have any questions or need assistance with processing their vote, please contact MacKenzie Partners, Inc. (email: proxy@mackenziepartners.com, or call toll free: 1-800-322-2885), Zynerba’s proxy solicitor.

First Quarter 2023 Financial Results
Research and development expenses were $7.1 million for the first quarter of 2023, including stock-based compensation of $0.4 million. General and administrative expenses were $3.4 million in the first quarter of 2023, including stock-based compensation expense of $0.4 million. Net loss for the first quarter of 2023 was $10.1 million, with basic and diluted loss per share of $(0.21).

Financial Outlook
As of March 31, 2023, cash and cash equivalents were $44.4 million, compared to $50.6 million as of December 31, 2022.

On May 11, 2021, the Company entered into a Controlled Equity Offering^SM Sales Agreement (2021 Sales Agreement), with Cantor Fitzgerald & Co., Canaccord Genuity, LLC, H.C. Wainwright & Co. LLC and Ladenburg Thalmann & Co. Inc., as sales agents, pursuant to which the Company may sell, from time to time, up to $75.0 million of its common stock. We are currently subject to General Instruction I.B.6 of Form S-3, and the amount of funds we can raise through primary public offerings of securities in any twelve-month period using our existing registration statement on Form S-3 is limited to one-third of the aggregate market value of the voting and non-voting common equity held by non-affiliates. We will be subject by this limit until such time as our public float exceeds $75.0 million. In the first quarter of 2023, the Company sold and issued 1,179,077 shares of its common stock under the 2021 Sales Agreement in the open market resulting in gross proceeds of $0.7 million and net proceeds of $0.6 million, after deducting commissions and offering expenses.

On July 21, 2022, the Company entered into a Purchase Agreement (2022 Purchase Agreement) and registration rights agreement for up to $20.0 million with Lincoln Park Capital Fund, LLC (LPC), a Chicago-based institutional investor. In the first quarter of 2023, the Company sold and issued 2,100,000 shares of its common stock under the 2022 Purchase Agreement resulting in gross and net proceeds of $1.1 million. From April 1, 2023 through May 11, 2023, the Company sold and issued 150,000 shares of common stock under the Purchase Agreement resulting in gross and net proceeds of $0.1 million.

Management believes that the Company’s cash and cash equivalents are sufficient to fund operations and capital requirements to mid-year 2024. Top-line results from the Company’s confirmatory pivotal Phase 3 RECONNECT trial of Zygel in patients with FXS are expected in the first half of 2024.

About Zygel
Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide consistent drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS) and 22q11.2 deletion syndrome (22q). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the Company’s ability to regain compliance with the requirements for continued listing on the Nasdaq Capital Market, including the risk of not obtaining stockholder approval for a potential reverse stock split; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation, banking stability or global instability, including political instability, may disrupt our business operations or our financial condition. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS
		(unaudited)
		Three months ended March 31,
			2023				2022
Operating expenses:
Research and development		$	7,078,081			$	5,146,605
General and administrative			3,393,094				3,757,310
Total operating expenses			10,471,175				8,903,915
Loss from operations			(10,471,175	)			(8,903,915	)
Other income (expense):
Interest income			447,315				96,044
Foreign exchange (loss) gain			(89,983	)			317,252
Total other income (expense)			357,332				413,296
Net loss		$	(10,113,843	)		$	(8,490,619	)
Net loss per share – basic and diluted		$	(0.21	)		$	(0.21	)
Basic and diluted weighted average shares outstanding			48,430,567				40,304,484
Non-cash stock-based compensation included above:
Research and development		$	373,626			$	529,496
General and administrative			448,360				630,986
Total		$	821,986			$	1,160,482

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED BALANCE SHEETS
		(unaudited)
		March 31, 2023				December 31, 2022
Assets
Current assets:
Cash and cash equivalents		$	44,400,344			$	50,640,993
Incentive and tax receivables			1,174,817				1,225,383
Prepaid expenses and other current assets			2,001,086				2,908,731
Total current assets			47,576,247				54,775,107
Property and equipment, net			473,270				409,572
Incentive and tax receivables			309,190				—
Right-of-use assets			277,826				336,215
Total assets		$	48,636,533			$	55,520,894
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable		$	2,142,216			$	1,942,830
Accrued expenses			7,251,414				7,014,882
Lease liabilities			216,385				214,901
Total current liabilities			9,610,015				9,172,613
Lease liabilities, long-term			59,967				119,524
Total liabilities			9,669,982				9,292,137
Stockholders’ equity:
Common stock			53,503				47,896
Additional paid-in capital			323,544,176				320,698,146
Accumulated deficit			(284,631,128	)			(274,517,285	)
Total stockholders’ equity			38,966,551				46,228,757
Total liabilities and stockholders’ equity		$	48,636,533			$	55,520,894

Zynerba Contacts
Jim Fickenscher, CFO and VP Corporate Development
Zynerba Pharmaceuticals
484.581.7483
fickenscherj@zynerba.com

Peter Vozzo
ICR Westwicke
443.213.0505
Peter.Vozzo@Westwicke.com

Zygel continued to be well-tolerated with long-term administration and maintained clinically meaningful improvements in children and adolescents with Fragile X syndrome

Zygel achieved statistically significant and clinically meaningful improvements from baseline in multiple efficacy assessments and was generally well-tolerated through 38 weeks of treatment in INSPIRE, a Phase 2 trial with Zygel in children and adolescents with 22q

DEVON, Pa., April 12, 2023 (GLOBE NEWSWIRE) — Zynerba Pharmaceuticals, Inc. (Nasdaq: ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders, is presenting two posters at the 55^th Gatlinburg Conference, being held April 10-13, 2023, in Kansas City, Mo. Copies of the posters are available on the Zynerba corporate website at www.zynerba.com/publications.

“New interim results from the open-label extension trial continue to support the long-term safety and sustained effectiveness of Zygel in children and adolescents with Fragile X syndrome (FXS), with the greatest improvements seen in those with complete methylation of their FMR1 gene, the population for the primary efficacy analysis in our pivotal RECONNECT trial,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “In addition, we believe data from the Phase 2 INSPIRE trial suggest the potential of Zygel as a treatment of anxiety and other behavioral symptoms in children and adolescents with 22q.”

The presentation titled, “Long-term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in Children and Adolescents with Fragile X Syndrome (ZYN2-CL-017),” includes data demonstrating that in the ongoing long-term safety and efficacy trial of Zygel in children and adolescents with FXS, Zygel was well-tolerated with long-term administration with up to 45 months of exposure. Patients with complete methylation, who match the primary efficacy population in the ongoing confirmatory trial, RECONNECT, achieved and maintained clinically meaningful changes in Social Avoidance over 24 months, further supporting this design enhancement for RECONNECT.

The poster titled, “An Open-Label Tolerability and Efficacy Study of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE),” shows that through 38-weeks of treatment, statistically significant improvements were seen in children and adolescents treated with Zygel in the Pediatric Anxiety Rating Scale (PARS-R), all five scales of the Anxiety, Depression and Mood Scale (ADAMS), and all five subscales of the Aberrant Behavior Checklist – Community (ABC-C). These results are consistent with the previously reported 14-week treatment data suggesting a positive risk-benefit profile for Zygel in improving anxiety-related and other behavioral symptoms in children and adolescents with 22q when added to standard of care.

About RECONNECT
RECONNECT is a Phase 3 trial of Zygel in patients with FXS ages 3 through 22 years. The trial was designed based upon learnings from the initial Phase 3 trial, CONNECT-FX, which demonstrated potential effectiveness of Zygel in patients with 100% methylation of their FMR1 gene. RECONNECT is actively enrolling participants 3 through 22 years of age. More information about the trial, including how to be contacted regarding potential participation, is available at www.fragilexhelp.com.

About Zygel
Zygel is the first and only pharmaceutically-manufactured cannabidiol formulated as a patent-protected permeation-enhanced clear gel, designed to provide consistent drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that cannabidiol may modulate the endocannabinoid system and improve certain behavioral symptoms associated with neuropsychiatric conditions. Zygel is an investigational drug product in development for the potential treatment of behavioral symptoms associated with Fragile X syndrome (FXS) and 22q11.2 deletion syndrome (22q). The Company has received orphan drug designation for cannabidiol, the active ingredient in Zygel, from the FDA and the European Commission in the treatment of FXS and the treatment of 22q. Additionally, Zygel has been designated a Fast Track development program for treatment of behavioral symptoms of FXS.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals is the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for orphan neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X syndrome and 22q11.2 deletion syndrome. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements, incentive and other tax credit eligibility, collectability and timing, and availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the U.S. Food and Drug Administration, the European Medicines Agency and other foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates; the extent to which health epidemics and other outbreaks of communicable diseases, including COVID-19, could disrupt our operations or adversely affect our business and financial conditions; and the extent to which inflation or global instability, including political instability, may disrupt our business operations or our financial condition. 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 Contacts
Peter Vozzo
ICR Westwicke
Office: 443.213.0505
Cell: 443.377.4767
Peter.Vozzo@Westwicke.com