Rubedo Reports Early Clinical Activity for GPX4 Modulator RLS-1496 in Actinic Keratosis

Key Takeaways

• Preliminary Phase 1b/2a data showed a 46% reduction in actinic keratosis lesion count with topical RLS-1496 at 4 weeks versus 11% in untreated controls.
• RLS-1496, a first-in-class glutathione peroxidase 4 (GPX4) modulator, was reported to be well tolerated with minimal local irritation and no serious adverse events.
• Rubedo Life Sciences plans to initiate a Phase 2b dose-ranging study of RLS-1496 for actinic keratosis in the fourth quarter of 2026.

Rubedo Life Sciences announced preliminary findings from a Phase 1b/2a trial evaluating topical RLS-1496 1% cream in adults with actinic keratosis (AK), reporting reductions in lesion counts alongside favorable tolerability data. The interim findings were presented at the RBC Capital Markets Global Healthcare Conference in New York City on May 19, 2026.

The open-label, multicenter study conducted in the United States evaluated RLS-1496 in patients with AK located on the forearms. According to the company, the first 18 of 24 evaluable patients demonstrated a 46% reduction in AK lesion count at 4 weeks compared with an 11% reduction in untreated controls. No serious adverse events or treatment discontinuations due to adverse events were reported during the study period. Investigators also reported minimal local irritation associated with treatment, an area that remains a challenge with currently available field therapies for AK.

EARLY RLS-1496 DATA SUGGEST POTENTIAL ALTERNATIVE FOR AK FIELD THERAPY

RLS-1496 is described by the company as the first selective GPX4 modulator studied in humans and part of a proposed therapeutic category termed “Adaptive SenoTherapeutics.” The therapy is designed to selectively target senescent and stressed aging cells through modulation of ferroptosis pathways.

“A 46% reduction in AK lesions at 4 weeks, achieved with minimal irritation, is exciting since so many patients are hesitant to use current treatments due to redness, peeling, pain, and weeks-long recovery,” said Frederick Beddingfield III, MD, PhD, FAAD, chief executive officer of Rubedo Life Sciences, in a company statement.

The company also referenced preliminary findings from a separate Phase 1b study conducted in the European Union involving patients with plaque psoriasis, atopic dermatitis, and photoaged skin. In that study, RLS-1496 reportedly met its primary safety endpoint and demonstrated a 20% decrease in epidermal thickness in psoriasis patients receiving active therapy compared with a 30% increase in patients receiving vehicle.

Rubedo stated that a Phase 2b dose-ranging study in AK is expected to begin in the fourth quarter of 2026. The company noted that additional data from approximately 70 subjects treated with RLS-1496 in aging skin studies are being compiled for submission to medical meetings and peer-reviewed journals.

“By clearing damaged senescent cells and restoring the health of stressed but viable cells, we aim to address biological aging at its cellular root, with implications that extend well beyond dermatology,” said Marco Quarta, PhD, chief scientific officer and founder of Rubedo Life Sciences, in the statement.