Zynerba Pharmaceuticals, Inc. provided program updates for Fragile X syndrome (FXS), autism spectrum disorder (ASD), 22q11.2 deletion syndrome (22q) and developmental and epileptic encephalopathies (DEE). In addition to the continued clinical development of Zygel in FXS, the Company plans to focus on the development of Zygel in ASD and 22q. Based on Company research and strategic prioritization, the decision has been made to not move forward in DEE at this time.

The Company continues to expect topline results from RECONNECT, a confirmatory pivotal Phase 3 trial of Zygel in patients with FXS, in the second half of 2023. The Company received written scientific advice from the European Medicines Agency (EMA) providing clarity and guidance on the clinical and regulatory requirements for the submission of a marketing authorization application (MAA) in the European Union (EU) for Zygel for the treatment of behavioral symptoms associated with FXS. Based on the EMA's scientific advice, the Company believes that the successful completion of the current development program for Zygel in FXS will satisfy the requirements of an MAA in the EU.

Presented data at the BRAIN Foundation Synchrony 2021 Symposium describing how Zygel may provide therapeutic benefit in FXS through its effects on the endocannabinoid system. The presentation included results from the Phase 3 CONNECT-FX trial demonstrating that Zygel was superior to placebo in multiple analyses in the groups of patients with either =90% methylation or complete methylation (100%) of their FMR1 gene. Data also showed that in the Company's ongoing open label extension study, Zygel continued to be well-tolerated, without reports of clinically significant changes in vital signs, ECGs or laboratories (including liver function) with a median length of treatment of 21 months.

The Company plans to advance its program in ASD with two Phase 3 trials, the first of which is expected to start in the second half of 2022. The Company is finalizing the Phase 3 study protocol and will submit an Investigational New Drug application to the U.S. Food and Drug Administration (FDA) prior to commencing the pivotal program. Previous discussions with the FDA included agreement on utilizing the irritability subscale of the Aberrant Behavior Checklist – Community (ABC-C) as the primary endpoint to support an indication for the treatment of irritability in ASD.

This is the same primary endpoint utilized in the pivotal trials for the two existing FDA approved treatments for ASD.