Rubedo Life Sciences' RLS-1496 shows positive Phase I results in plaque psoriasis and atopic dermatitis

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](https://www.businesswire.com/news/home/20260326810310/en/Rubedo-Life-Sciences-Announces-Positive-Preliminary-Phase-1-Clinical-Trial-Results-for-Lead-Drug-Candidate-RLS-1496-in-Patients-with-Plaque-Psoriasis-Atopic-Dermatitis-and-Skin-Aging) 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 company did not disclose the total number of patients enrolled in this study, nor did it report formal efficacy endpoints or statistical comparisons between active and vehicle arms beyond the correlations described. The [trial](https://www.allsci.com) was designed primarily to assess safety, tolerability, plasma bioavailability, and pharmacodynamics of topical RLS-1496 across three indications simultaneously. The company did not report the number of subjects per cohort or per indication, and 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](https://www.allsci.com) and [risankizumab](https://www.allsci.com) 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. --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/rls-1496-phase-i-results-rubedo-life-sciences)