Rubedo describes RLS-1496 as “a first-in-class GPX4 modulator that targets aging cells and surrounding tissues.” GPX4 (glutathione peroxidase 4) is an antioxidant enzyme that protects cells against oxidative stress by using reduced glutathione to catalyze the reduction of pro-oxidant hydrogen peroxide, organic hydroperoxides, and lipid peroxides. While Rubedo has not proposed the mechanism of RLS-1496, scientists at LRI and others have shown that senescent cells are primed for death via ferroptosis, a distinctive form of cell death involving lipid peroxides, but resist death by upregulating GPX4 among other adaptations. Accordingly, drugs that inhibit GPX4 are known to cause selective cell death in senescent and some cancer cells.
In March 2023, Rubedo announced that affiliated scientists had presented animal data on an unspecified lead compound during the 2023 American Academy of Dermatology (AAD) conference week. According to the press release, this compound reduced signatures associated with skin senescent cells in vivo “and significantly improved skin pathophysiological manifestations, such as chronic desquamation in preclinical animal models of chemotherapy-induced skin fibrosis and dermatitis.” The company highlighted its potential as a treatment for a range of dermatological diseases.
In May 2023, Rubedo committed to advancing its lead candidate RLS-1496 into IND-enabling studies for dermatological indications, with first-in-human studies planned for early 2024. Rubedo stated that RLS-1496 “significantly reduced senescence signatures associated with skin senescent cells, and in punch biopsies from skin lesions of patients with chronic atopic dermatitis and psoriasis.”
As part of the partnership with Beiersdorf AG, Beiersdorf will conduct in vitro and in silico studies — and ultimately in vivo human studies — on Rubedo’s.lead compounds in cosmetic formulations.
In April 2024, Rubedo announced that it had closed a $40M Series A financing round, with which it would advance RLS-1496 into Phase I studies in chronic atopic dermatitis and chronic psoriasis within that calendar year.
In January 2025, Rubedo announced that it had presented its clinical development plans for RLS-1496 at the 12th Annual Dermatology Summit, including details for its Phase I trial of the drug, which they anticipated commencing in Spring 2025. No details on the trial were included in the announcement.
In May 2025, Rubedo announced that it had dosed its first patient with topical RLS-1496 in its Phase I clinical trial in adults with plaque psoriasis. Depending on the results, Rubedo stated that the trial could expand to include “additional inflammatory skin conditions and autoimmune disorders, including but not limited to atopic dermatitis, vitiligo, rosacea, alopecia areata, and scleroderma.” It highlighted that the company had developed “RLS-1496 into a topical drug candidate in less than three years from initiation – two times faster than the industry average.” However, their source for this comparison does not seem to address topical drugs. The company anticipates having results from this trial in Q4 2025.
In September 2025, Rubedo announced that FDA had cleared its Investigational New Drug (IND) application for a Phase Ib/IIa trial of RLS-1496 in patients with actinic keratosis. The company anticipates initiating this trial in Q4 2025.
