BD2-Selective BET Inhibitor VYN202 Demonstrates Positive Safety and Tolerability in Phase 1a Trial

VYNE Therapeutics Inc. announced today that its novel oral small molecule, BD2-selective bromodomain, and extra-terminal domain (BET) inhibitor, VYN202, demonstrated favorable safety, tolerability, pharmacokinetics, and pharmacodynamics in a phase 1a placebo-controlled single-ascending dose (SAD) clinical trial.¹

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VYN202 is currently in development for immuno-inflammatory diseases, with current focuses on generating proof of principle in psoriasis and arthritis. In June, VYNE announced it had completed initial dosing of participants.²

The phase 1a trial consists of 2 parts, including the above described SAD portion and multiple ascending dose (MAD) components.

In the SAD portion of the trial, VYN202 exhibited a favorable safety profile across various dose levels, with no serious adverse events or abnormalities reported in laboratory results. The drug exhibited a dose-dependent increase in plasma and urine concentrations, aligning with expected pharmacokinetic parameters.

Additionally, pharmacodynamic assessments revealed that VYN202 effectively engaged its target proteins, as indicated by elevated HEXIM1 levels. Furthermore, preliminary data from the SAD phase suggested that VYN202 has potential biological activity, including an inhibitory effect on inflammatory biomarkers associated with conditions like psoriasis and rheumatoid arthritis.

"These results from our SAD trial mark the first clinical data for our BD2-selective BET inhibitor, VYN202, and represent an important milestone for our Company and the development of our BET inhibitor platform," said David Domzalski, president and chief executive officer of VYNE, in a news release.¹

Researchers have already commenced dosing for the MAD portion of the trial, with results anticipated in quarter 4 of 2024. This phase will evaluate VYN202's safety, tolerability, pharmacokinetics, and pharmacodynamic over a 14-day period at varying doses.

"We look forward to further assessing safety and [pharmacokinetics] as well as VYN202’s potential to impact several relevant biomarkers following multiple doses," Domzalski said. "These data would inform the design of our planned studies in psoriasis and rheumatoid arthritis."

In a previous interview with Dermatology Times, Iain Stuart, PhD, chief scientific officer of VYNE, expressed excitement at the potential implications of VYN202 in the immuno-inflammatory disease landscape and armamentarium.

"We think VYN202 has a very broad applicability based on a preclinical data that were generated to date. Thinking even beyond moderate or severe psoriasis and arthritis, we see this direct application to other autoimmune diseases, both within dermatology and outside of dermatology," Stuart said. "The parallel we like to look at is how broadly JAK inhibitors, for example, have been applied over the years. We see a similar potential path for BET inhibitors, as well. Clearly, we are hyper focused at the moment in generating proof of principle data in psoriasis and in arthritis, but clearly, with many opportunities beyond that, to really maximize the potential value to patients for VYN202."

References

1. VYNE Therapeutics announces positive phase 1a SAD data for VYN202, a novel BD2-Selective BET inhibitor. News release. BioSpace. September 12, 2024. Accessed September 12, 2024. https://www.biospace.com/press-releases/vyne-therapeutics-announces-positive-phase-1a-sad-data-for-vyn202-a-novel-bd2-selective-bet-inhibitor
2. VYNE therapeutics announces dosing of first participants in phase 1a trial of novel BD2-selective BET inhibitor VYN202. News release. VYNE Therapeutics. June 13, 2024. Accessed September 12, 2024. https://vynetherapeutics.com/press-releases/vyne-therapeutics-announces-dosing-of-first-participants-in-phase-1a-trial-of-novel-bd2-selective-bet-inhibitor-vyn202/