FDA Places Clinical Hold on VYNE’s VYN202 Phase 1b Trial for Plaque Psoriasis

VYNE Therapeutics Inc. announced today a pause in development in its clinical pipeline: the US FDA has issued a verbal notice of clinical hold on the company’s ongoing phase 1b trial evaluating VYN202, an investigational oral bromodomain and extra-terminal domain (BET) inhibitor for moderate to severe plaque psoriasis.¹ The hold was prompted by testicular toxicity observed in a recent non-clinical toxicology study with VYN202 in canines.

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As a precautionary measure, VYNE has immediately suspended all patient screening, enrollment, and dosing in the phase 1b trial. To date, no serious adverse events have been reported in human subjects participating in the study.

"While we are disappointed by this unexpected development, the safety and well-being of patients in our studies is our top priority," David Domzalski, president and chief executive officer of VYNE, said in a news release.¹ "We intend to work closely with the FDA to address the clinical hold as expeditiously as possible and we plan to provide additional updates pending continued engagement with FDA."

A Disruption in a Promising Program

The clinical hold comes 2 months after VYNE announced the launch of the phase 1b study of VYN202 in patients with moderate to severe plaque psoriasis.² The randomized, double-blind, placebo-controlled trial was designed to enroll approximately 80 participants over a 12-week treatment period, followed by a 4-week safety follow-up. Doses of 0.25 mg, 0.5 mg, and 1 mg were being evaluated against placebo. Primary endpoints included safety and tolerability, while secondary measures focused on pharmacokinetics and preliminary efficacy assessments such as Psoriasis Area and Severity Index scores and physician global assessments.

The trial was greenlit based on encouraging phase 1a single-ascending dose (SAD) and multiple-ascending dose (MAD) data reported in late 2024.³ In those early trials, VYN202 demonstrated a favorable safety profile, robust pharmacokinetics, and target engagement, including modulation of inflammatory biomarkers implicated in psoriasis and other immune-mediated diseases.

In December 2024, Dermatology Times reported that the MAD portion of the phase 1a study found no serious adverse events or dose-limiting toxicities. The compound successfully elevated HEXIM1 levels—a biomarker of BET inhibition—and reduced Th17, TNF, and Th1-related inflammatory signals. No significant drug interactions were observed in subjects co-administered methotrexate.

"We believe the data from this phase 1a SAD/MAD trial validates our drug design thesis for VYN202," said Domzalski at the time.³

Vitiligo Program Unaffected

VYNE confirmed that the clinical hold does not impact its other investigational program, repibresib gel for nonsegmental vitiligo. Repibresib is a distinct molecule with a separate mechanism of action. A phase 2b trial for repibresib gel remains on track, with top-line results from the 24-week double-blind, vehicle-controlled phase expected by mid-2025.

Next Steps

VYNE has not disclosed the duration of the hold or specific regulatory requirements needed to lift it, but the company expressed its intent to work closely with the FDA and provide timely updates.

References

1. VYNE Therapeutics provides update on VYN202 programh. News release. Globe Newswire. April 25, 2025. Accessed April 25, 2025. https://www.globenewswire.com/news-release/2025/04/25/3068263/0/en/VYNE-Therapeutics-Provides-Update-on-VYN202-Program.html?f=22&fvtc=5&fvtv=46688798
2. VYNE Therapeutics initiates phase 1b trial of VYN202, a novel BD2-selective oral BET inhibitor, in plaque psoriasis. News release. Globe Newswire. February 19, 2025. Accessed April 25, 2025. https://www.globenewswire.com/news-release/2025/02/19/3028700/0/en/VYNE-Therapeutics-Initiates-Phase-1b-Trial-of-VYN202-a-Novel-BD2-Selective-Oral-BET-Inhibitor-in-Plaque-Psoriasis.html
3. 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 April 25, 2025. https://www.biospace.com/press-releases/vyne-therapeutics-announces-positive-phase-1a-sad-data-for-vyn202-a-novel-bd2-selective-bet-inhibitor