Zygel (cannabidiol gel) / Paragon Biosciences - LARVOL DELTA

ZYN2-CL-017: Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS (clinicaltrials.gov) - P2/3 | N=476 | Active, not recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Aug 2027 ➔ Jun 2026 | Trial primary completion date: Aug 2027 ➔ Jun 2026

Enrollment closed • Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders

Phase 2, open-label INSPIRE trial to assess the tolerability and effectiveness of transdermal cannabidiol gel in children and adolescents with 22q11.2 deletion syndrome (ZYN2-CL-031). (PubMed, J Neurodev Disord) - No abstract available

Journal • P2 data • Immunology • Mood Disorders • Primary Immunodeficiency • Psychiatry

Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE) (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Harmony Biosciences Management, Inc. | Phase classification: P1/2 ➔ P2

Phase classification • Immunology • Primary Immunodeficiency

ZYN2-CL-017: Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Zynerba Pharmaceuticals, Inc.

New P2/3 trial • Fragile X Syndrome • Genetic Disorders

ZYN2-CL-017: Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS (clinicaltrials.gov) - P2/3 | N=450 | Enrolling by invitation | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: May 2027 ➔ Aug 2027 | Trial primary completion date: May 2027 ➔ Aug 2027

Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders

ZYN2-CL-017: Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS (clinicaltrials.gov) - P2/3 | N=450 | Enrolling by invitation | Sponsor: Zynerba Pharmaceuticals, Inc. | N=300 ➔ 450

Enrollment change • Fragile X Syndrome • Genetic Disorders

ZYN2-CL-017: Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS (clinicaltrials.gov) - P2/3 | N=300 | Enrolling by invitation | Sponsor: Zynerba Pharmaceuticals, Inc. | Recruiting ➔ Enrolling by invitation

Enrollment status • Fragile X Syndrome • Genetic Disorders

ZYN2-CL-017: Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: Sep 2020 ➔ Feb 2022 | Trial primary completion date: Sep 2019 ➔ Feb 2022

Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders

Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates (clinicaltrials.gov) - P1 | N=29 | Completed | Sponsor: Harmony Biosciences Management, Inc. | Recruiting ➔ Completed

Trial completion

RECONNECT: Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (clinicaltrials.gov) - P3 | N=215 | Completed | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: May 2025 ➔ Aug 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders • FMR1

Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study. (PubMed, J Neurodev Disord) - P2/3 | "Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS."

Clinical • Journal • Dermatology • Fragile X Syndrome • Genetic Disorders • Pain

Efficacy and Safety of Topical 5% Cannabidiol Plus Myrcene for the Treatment of Vestibulodynia: A Multi-Centric Randomized Controlled Trial. (PubMed, Biomedicines) - " This was a randomized double-blind trial involving patients who applied a 5% cannabidiol gel with myrcene or a placebo to their vulvar vestibule for 60 days, assessing changes in dyspareunia, pain, and vestibular cotton swab test scores on a 0-10-point VAS scale...It desensitizes transient vanilloid receptor potential channels subtype 1, which are found in peripheral C-fiber nociceptors and mast cells. The results also suggest that myrcene, a terpene found in cannabis, can inhibit peripheral sensitization exerted by cannabidiol."

Journal • Neuralgia • Pain • Women's Health

Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Harmony Biosciences Management, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Effect of an Experimental Cannabidiol Gel on Tooth Sensitivity (clinicaltrials.gov) - P1 | N=75 | Not yet recruiting | Sponsor: Universidade Federal do Para

New P1 trial

RECONNECT: Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (clinicaltrials.gov) - P3 | N=250 | Active, not recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Fragile X Syndrome • Genetic Disorders • FMR1

Drug Interaction Study of ZYN002 Transdermal Gel and Probe Substrates (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: Harmony Biosciences Management, Inc.

New P1 trial

Long-term Safety and Effectiveness of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Irritability-Related Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome: Update to Open-Label Extension Study (ZYN2-CL-017) (S31.007). (PubMed, Neurology) - P2/3 | "Dr. Nomikos has received personal compensation for serving as an employee of Harmony Biosciences."

Clinical • Journal • Behavior Disorders • Fragile X Syndrome • Genetic Disorders • Pain

Long-term Safety and Effectiveness of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Irritability-Related Behavioral Symptoms in Children and Adolescents with Fragile X Syndrome: Update to Open-Label Extension Study (ZYN2-CL-017) (AAN 2025) - P2/3 | "ZYN002 has a favorable safety profile and is generally well tolerated. Secondary results support further study of ZYN002 in patients with FXS."

Clinical • Behavior Disorders • Fragile X Syndrome • Genetic Disorders • Pain

Harmony Biosciences Reports Strong 2024 Financial Results and Reiterates 2025 Net Revenue Guidance; Highlights 2025 Catalysts in Sleep/Wake and Fragile X Syndrome Development Programs (Businesswire) - "Topline data readout from Phase 3 registrational trial of ZYN002 in FXS (RECONNECT study) in Q3 2025 with potential PDUFA date in 2026; Phase 3 registrational trial in 22q11.2 deletion syndrome (22q) to initiate in 2025...EPX-100 (clemizole hydrochloride}....Topline data readout from Phase 3 registrational trial in Dravet syndrome (ARGUS Study) anticipated in 2026; Topline data for Phase 3 registrational trial in patients with Lennox-Gastaut syndrome (LIGHTHOUSE study) anticipated in 2026."

New P3 trial • P3 data: top line • Epilepsy • Fragile X Syndrome

Long-Term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Irritability-Related Behavioral Symptoms in Children, Adolescents, and Young Adults With Fragile X Syndrome: Update to Open-Label Extension Study (AACAP 2024) - P2/3 | "Consistent with previous analyses of the OLE data, ZYN002 has been generally well tolerated and results have continued to support its effectiveness in improving behavioral symptoms of FXS.DBD, ND, PTA"

Clinical • Behavior Disorders • Fragile X Syndrome • Genetic Disorders • Pain

2024 Update to the Long-term Safety and Sustained Efficacy of ZYN002 Cannabidiol Transdermal Gel in the Treatment of Behavioral Symptoms in Children, Adolescents, and Young Adults with Fragile X Syndrome (ZYN2-CL-017) (NFXF-FXC 2024) - "The results being presented are from the open-label extension (OLE) trial ZYN2-CL-017. The data collected through 31-January-2024 will assess both safety and efficacy in patients entering the OLE from the CONNECT-FX, FAB-C, and RECONNECT trials with forthcoming results and conclusions."

Clinical • Fragile X Syndrome • Genetic Disorders

RECONNECT: Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (clinicaltrials.gov) - P3 | N=204 | Recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: Mar 2024 ➔ May 2025 | Trial primary completion date: Mar 2024 ➔ May 2025

Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders • FMR1

HARMONY BIOSCIENCES TO PRESENT RESULTS FROM BEHAVIORAL STUDY IN 22Q11.2 DELETION SYNDROME AT AMERICAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY ANNUAL MEETING (PRNewswire) - "Harmony Biosciences Holdings, Inc...will present caregiver-reported impacts of 22q11.2 deletion syndrome (22q) and data from the Phase 2 INSPIRE trial at the American College of Neuropsychopharmacology Annual Meeting from December 3-6, 2023."

P2 data • CNS Disorders • Genetic Disorders

RECONNECT: Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (clinicaltrials.gov) - P3 | N=204 | Recruiting | Sponsor: Zynerba Pharmaceuticals, Inc. | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Sep 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Fragile X Syndrome • Genetic Disorders • FMR1

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) (AACAP 2023) - "In patients with complete FMR1 methylation, ZYN002 led to sustained improvement in SA. The results from this trial continue to support the effectiveness of ZYN002 in patients with complete FMR1 methylation."

Clinical • Fragile X Syndrome • Genetic Disorders • Pain • FMR1