VYNE Therapeutics’ VYN202, which is under development for treating chronic inflammatory and immune-mediated conditions, performed well in the single ascending dose part of an ongoing Phase 1a trial, the Company reports.

VYN202 was generally well tolerated with no drug-related adverse events, and pharmacokinetic results demonstrated dose-dependent exposure of VYN202 in blood.

VYN202 is an oral small molecule bromodomain (BRD) and extra-terminal (BET) inhibitor that has selectivity and potency for beta‐defensin‐2 (BD2) vs. BD1. By maximizing BD2 selectivity, VYN202 may be a more conveniently administered non-biologic treatment option for both acute control and chronic management of immuno-inflammatory indications such as psoriasis.

The Phase 1a trial is a two-part, double-blind, placebo-controlled dose-escalation study in healthy volunteers consisting of single ascending dose and multiple ascending dose components to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of VYN202.

Findings from the single ascending dose part of the Phase 1a trial to date are as follows:

VYN202 Was Generally Well Tolerated Across All Dose Groups

Single ascending doses of VYN202 across all cohorts were generally well tolerated up to and including the highest planned dose level. There were no serious adverse events, drug-related adverse events, or clinically significant abnormalities in clinical laboratory results or electrocardiogram findings.

VYN202 Demonstrated Dose-Dependent Pharmacokinetics

VYN202 also met expected pharmacokinetics parameters, with plasma and urine drug concentrations of VYN202 increasing in a dose-dependent manner across all doses tested.

VYN202 Demonstrated Pharmacodynamic Effects

Participant blood samples were stimulated ex-vivo to assess the pharmacodynamic impact of single doses of VYN202 on key target-engagement and inflammatory biomarkers. Results demonstrated an increase in marker protein HEXIM1, indicative of target engagement of VYN202 with BET proteins. Additionally, exploratory data from the single ascending dose arm showed that single doses of VYN202 demonstrated biological activity and an inhibitory effect on select inflammatory biomarkers relevant to psoriasis and rheumatoid arthritis.

Phase 1a Multiple Ascending Dose Part of Trial Initiated

The primary objectives of the multiple ascending dose part of the Phase 1a trial are to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of VYN202 over 14 days at different dose levels.

Results are expected in Q4 2024.

“We look forward to further assessing safety and PK as well as VYN202’s potential to impact several relevant biomarkers following multiple doses, which we expect to disclose next quarter,” says David Domzalski, President and Chief Executive Officer of VYNE, in a news release. “These data would inform the design of our planned studies in psoriasis and rheumatoid arthritis.”