VYNE Therapeutics Reports Positive Phase 1a MAD Data for BD2-Selective BET Inhibitor VYN202

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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 multiple-ascending dose (MAD) clinical trial.¹ The drug is being developed to treat chronic inflammatory and immune-mediated conditions such as psoriasis and arthritis.

“We are very excited by the PK, pharmacodynamic and safety data generated in this trial which not only support the further development of VYN202 but also give us increased confidence that VYN202 has the potential to become a novel treatment option for immune-mediated diseases,” said David Domzalski, President and Chief Executive Officer of VYNE, in a news release.¹

The Phase 1a, q-part, double-blind, dose-escalation study tested the drug across a 14-day period in healthy volunteers. In the MAD portion of the trial, VYN202 exhibited a favorable safety profile across various dose levels (0.5mg QOD, 0.5mg QD, 1mg QD, and 1mg QD) with no serious adverse events, discontinuations, or abnormalities reported in laboratory results. 

Additionally, VYN202 demonstrated a favorable pharmacokinetics profile, and no drug interactions were reported in participants who also took methotrexate. It also effectively engaged its target proteins, as indicated by elevated HEXIM1 levels, and inhibited the production of multiple inflammatory biomarkers related to Th17, Th1/myeloid, and Th1/Tc dysregulated activity. These results align with what was discovered in the single-ascending dose portion of the trial back in September.²

“VYN202 has been designed to address the adverse events that have been historically associated with early generation BET inhibitors. We believe the data from this Phase 1a SAD/MAD trial validates our drug design thesis for VYN202. Based on these positive results, we look forward to finalizing our clinical trial plans for VYN202 in patients over a longer duration of treatment,” Domzalski added.¹

In a previous interview with Dermatology Times, Iain Stuart, PhD, chief scientific officer of VYNE, spoke about the key objectives of the MAD portion of the trial and its impact on VYN202’s next stages of development.

“Obviously, we have a single dose, but what happens after 14 doses? Is there significant accumulation? Is there a time to a steady-state blood level? Is that within 2 weeks? Is it potentially longer?” Stuart said. “Many questions could be addressed in the multiple ascending dose. Then correspondingly, once we complete the multiple ascending dose, that will certainly be very informative for dose selection, medical studies, and psoriasis.”

References

1. VYNE Therapeutics Reports Positive Top-line Phase 1a MAD Data for VYN202, its 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 positive phase 1a SAD data for VYN202, a novel BD2-Selective BET inhibitor. News release. BioSpace. December 23, 2024. Accessed December 23, 2024. https://www.biospace.com/press-releases/vyne-therapeutics-announces-positive-phase-1a-sad-data-for-vyn202-a-novel-bd2-selective-bet-inhibitor