Rubedo Life Sciences, based in Mountain View, California, reported preliminary results from a Phase I clinical trial of RLS-1496, a topical GPX4 modulator, in patients with plaque psoriasis, atopic dermatitis, and photo-aged skin. The single-center, ascending-dose, randomized, double-blind, vehicle-controlled study, conducted in the EU, met its primary endpoint for safety and tolerability, with the company also reporting early signs of clinical activity across all three conditions, according to a press release issued March 26. This is the first human trial of a GPX4 modulator and the first to test a therapy designed to selectively clear senescent cells in dermatologic disease.
Over the four-week treatment period, no serious adverse events and no discontinuations due to adverse events or tolerability were reported across three dose levels (0.1%, 0.5%, and 1.0%). In psoriasis patients, the company reported a dose-response relationship, dose-related target engagement, and an average 20% reduction in epidermal thickness on histology at the 1.0% dose. A statistically significant relationship between target engagement and clinical psoriasis severity improvement was observed, and reductions in senescent cells in mid- and high-dose cohorts were associated with decreases in inflammatory cytokines including IL-19 and S100A7 — changes not seen in the vehicle cohort.
In atopic dermatitis, the company reported higher target engagement and clinical improvement relative to psoriasis; 25% of RLS-1496-treated subjects achieved a four-point or greater reduction on the pruritus numeric rating scale at one month, compared with none in the vehicle group. In photo-aged skin, dose-dependent target engagement was observed, with spatial transcriptomics indicating increased collagen gene expression in dermal fibroblasts and decreased senescence-associated secretory phenotype markers in keratinocytes.
The trial was designed primarily to assess safety, tolerability, plasma bioavailability, and pharmacodynamics of topical RLS-1496 across three indications simultaneously, enrolling 44 patients. Full data are expected to be presented at the Society for Investigative Dermatology meeting in May 2026. A separate Phase Ib/IIa study in actinic keratosis is underway in the United States, with completion expected later in 2026; across both trials, Rubedo expects to collect photo-aging data from approximately 70 subjects. The data remain preliminary and are based on a four-week treatment duration with undisclosed sample sizes per arm.
RLS-1496 is designed to modulate GPX4 to sensitize pathologic senescent cells to ferroptosis, a form of programmed cell death. In the plaque psoriasis treatment landscape, established systemic therapies such as secukinumab and risankizumab have demonstrated PASI 90 response rates exceeding 70% in Phase III trials over 12 to 16 weeks, though these are systemic biologics studied in different populations and over longer durations than a four-week topical Phase I study. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.