VYNE Unblinds Early VYN202 Data After Safety Pause

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A recent announcement from VYNE Therapeutics highlight the evolving clinical trajectory of VYN202, an investigational oral BD2-selective bromodomain and extra-terminal domain (BET) inhibitor. The drug, being developed for immune-mediated diseases including moderate to severe plaque psoriasis, encountered a clinical hold in April 2025 after non-clinical data in dogs raised safety concerns.¹ However, the company says updated findings and preliminary human data suggest that VYN202 may still hold significant potential in treating immune-driven dermatologic and rheumatologic conditions.²

Clinical Hold and Safety Reassessment

The US Food and Drug Administration (FDA) imposed a clinical hold on VYNE’s phase 1b study following the observation of testicular toxicity in a non-clinical toxicology study involving dogs. Notably, the no-observed-adverse-effect level (NOAEL) established in female animals supported continued testing in female patients at 0.25 mg and 0.5 mg doses. The higher 1 mg dose was excluded from the amended trial design due to a less favorable toxicological margin. The FDA has since lifted the clinical hold for these 2 lower doses—but only in female subjects—pending additional toxicology data to support resumption in male participants.²

The hold prompted VYNE to unblind early clinical data, enabling preliminary evaluation of safety and efficacy outcomes across the limited number of patients already enrolled.

Early Phase 1b Outcomes

The phase 1b study enrolled 7 subjects in total—6 received VYN202 (across 0.25 mg, 0.5 mg, and 1 mg doses), and 1 received placebo. Safety results from this small cohort were encouraging: no treatment-emergent serious adverse events (TESAEs), no study discontinuations due to adverse events, and no hematologic toxicities such as thrombocytopenia or lymphocytopenia were reported.

Importantly, all VYN202-treated subjects experienced some clinical improvement in psoriasis symptoms, including scalp involvement. Reductions in Psoriasis Area and Severity Index (PASI) scores ranged from approximately 27% after one week to as high as 90% at week eight, suggesting a potential dose- and time-dependent response.

Serum biomarkers also showed promising trends. Pro-inflammatory cytokines commonly associated with plaque psoriasis—including IL-17A, IL-17F, IL-19, and IL-22—decreased by up to 83% in treated patients, while no significant changes were observed in the placebo subject. VYNE says these molecular improvements bolster the hypothesis that VYN202 exerts immunomodulatory effects by selectively targeting BD2, a domain implicated in inflammatory signaling.

Psoriatic Arthritis Signal

Interestingly, researchers reported 2 subjects presenting with concurrent psoriatic arthritis. One, treated with VYN202 0.5 mg, reported a 4-point reduction on the joint pain numeric rating scale by week 2, accompanied by a 48% reduction in serum C-reactive protein (CRP)—a key biomarker in rheumatic disease. The placebo subject reported no such improvement, further suggesting potential for broader therapeutic application of VYN202 beyond cutaneous psoriasis.

Strategic Program Shift

Despite these positive signals, VYNE has opted to discontinue enrollment in the current psoriasis-focused phase 1b study. This decision is framed as both a risk mitigation strategy and a cost-saving measure, intended to extend the company’s cash runway into Q4 2026. VYNE plans to redirect attention toward other immune-mediated conditions and will await topline results from its ongoing phase 2b trial of repibresib (formerly VYN201) in non-segmental vitiligo before announcing next steps for VYN202.

Conclusion

VYN202’s early clinical data suggest potential as a novel, orally available, BD2-selective BET inhibitor with immunomodulatory effects in plaque psoriasis and possibly psoriatic arthritis. While animal toxicology concerns have necessitated a temporary, sex-specific pause in clinical advancement, the company states the compound’s strong efficacy signals and biomarker improvements support continued exploration in immune-mediated conditions. Future development will hinge on further safety clarification and strategic alignment with unmet needs in dermatology and beyond.

References

1. VYNE Therapeutics provides update on VYN202 program. News release. Globe Newswire. April 25, 2025. Accessed July 7, 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 provides program update on oral BET inhibitor VYN202. News release. VYNE Therapeutics. July 2, 2025. Accessed July 7, 2025. https://vynetherapeutics.com/uncategorized/vyne-therapeutics-provides-program-update-on-oral-bet-inhibitor-vyn202/