BRIDGEWATER, N.J., March 30, 2023 (GLOBE NEWSWIRE) — VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced positive first-in-human pharmacokinetic and hematology data from its Phase 1a single and multiple ascending dose trial for its investigational novel BET inhibitor, VYN201. In February 2023, the Company announced positive preliminary safety and tolerability data from the trial.
The Phase 1a portion of the trial included comprehensive pharmacokinetic sampling to ascertain the exposure to topically-applied VYN201 from single and repeat treatment of VYN201 over five ascending dose cohorts. Results have shown that there were no quantifiable VYN201 plasma concentrations above the assay lower limit of quantification (0.25ng/ml).
Inhibiting the functionality of the bromodomain 1 (BD1) subunit of BET proteins is believed to disrupt homeostatic gene regulation. This can lead to potential clinical safety concerns such as thrombocytopenia (low platelet count), a known dose-limiting adverse event for systemically administered pan-BD BET inhibitors. In the Phase 1a trial, there was no evidence of low or lower platelet counts at any timepoint for any dose cohort. The assay lower limit of quantification (LLOQ) of 0.25ng/ml is 720-fold below the free half maximal effective concentration (EC50) for VYN201 against the BD1 domain of the BET protein, BRD4. There was no effect on other assessed clinical hematological parameters.
“These data, showing minimal systemic exposure of VYN201 with no effect on platelet counts, mark an important milestone in our development of VYN201 as a topically-administered pan-BD BET inhibitor,” said Dr. Iain Stuart, Chief Scientific Officer of VYNE. “These findings support our “soft” drug approach to treating patients with nonsegmental vitiligo, particularly in light of some of the potential safety concerns with current topical therapies and oral therapies in development.”
Enrollment in the Phase 1b portion of the trial is ongoing and the Company expects to report topline results in mid-2023.
About the Phase 1a/b Trial in Healthy Volunteers and Patients with Nonsegmental Vitiligo
In the Phase 1a portion of the study, single ascending and multiple ascending doses of VYN201 were applied topically once daily to 30 healthy volunteers in five dose cohorts (0.025%, 0.1%, 0.5%, 1.0% and 2.0% ointment strengths) over a two-week treatment period with a one-week safety follow-up visit to evaluate the safety, tolerability and pharmacokinetics of VYN201. The safety and tolerability results are summarized below:
- There were no serious adverse events and no dose adjustments were required.
- There were no clinically relevant treatment emergent adverse events, abnormal clinical laboratory results or electrocardiogram findings.
- No healthy volunteers withdrew from the trial for any reason.
- Based on the Phase 1a results, VYNE selected 0.5%, 1.0% and 2.0% ointment strengths for evaluation in the ongoing Phase 1b study. In this portion of the study, up to 30 patients with a clinical diagnosis of non-segmental vitiligo will receive VYN201 once daily in three dose cohorts. The primary objective of the
- Phase 1b portion of the study will be to evaluate the safety and pharmacokinetics of VYN201. Exploratory efficacy of VYN201 in non-segmental vitiligo patients will also be evaluated, including F-VASI, pharmacodynamic biomarkers and clinical photography.