Rubedo Life Sciences Reports Encouraging Phase I Results for RLS-1496 in Plaque Psoriasis, Atopic Dermatitis, and Aging Skin
Rubedo Life Sciences, a clinical-stage biotechnology company focused on developing innovative therapies targeting cellular aging, has reported encouraging preliminary findings from its Phase I clinical trial of RLS-1496. This investigational therapy is being evaluated for the treatment of plaque psoriasis, atopic dermatitis, and photoaged (aging) skin. The study marks a significant milestone, as RLS-1496 represents the first GPX4 (glutathione peroxidase 4) modulator to be tested in humans, introducing a novel therapeutic mechanism aimed at selectively targeting senescent, or pathologically aging, cells.
The Phase I trial was conducted in the European Union as a single-center, randomized, double-blind, excipient-controlled, dose-escalation study. Its primary objectives were to assess the safety, tolerability, pharmacodynamics, and preliminary efficacy of RLS-1496 when administered as a topical treatment. The trial successfully met its primary endpoint, demonstrating that the drug was well tolerated and exhibited early signals of clinical benefit across multiple skin conditions.
Importantly, no serious adverse events were reported during the four-week treatment period. Additionally, the study was not terminated due to safety or tolerability concerns, further supporting the favorable safety profile of RLS-1496. These results are particularly notable given the early stage of clinical development and the complexity of targeting cellular aging mechanisms.
In patients with plaque psoriasis, the study revealed clear dose-response relationships across three concentrations of RLS-1496 (0.1%, 0.5%, and 1.0%). All doses were well tolerated, but based on observed efficacy trends, future studies will focus on the 1.0% concentration. The drug demonstrated dose-dependent engagement with its target, GPX4, and led to a measurable reduction in the number of senescent cells in the skin, particularly in the medium- and high-dose groups.
This reduction in senescent cells was associated with decreased levels of inflammatory biomarkers, including IL-19 and S100A7, which are commonly elevated in inflammatory skin conditions. Notably, these changes were not observed in the control group, highlighting the potential therapeutic effect of RLS-1496. Histological analysis further supported these findings, showing an average reduction of approximately 20% in epidermal thickness among treated patients after one month. The study also identified a statistically significant correlation between target engagement and improvements in clinical disease severity, reinforcing the drug’s proposed mechanism of action.
Among patients with atopic dermatitis, RLS-1496 also demonstrated promising results. Higher levels of target binding were associated with meaningful clinical improvements. One of the key measures used in this group was the Numerical Rating Scale (NRS) for pruritus (itch severity). After one month of treatment, 25% of patients receiving RLS-1496 experienced a reduction of at least four points on the NRS, indicating substantial relief from itching. In contrast, none of the patients in the placebo group achieved a similar level of improvement.
The study also explored the effects of RLS-1496 on photoaged skin, providing early insights into its potential as an anti-aging therapy. Results showed dose-dependent target engagement even in non-lesional skin. Advanced analyses, including histological, proteomic, and spatial transcriptomic assessments, revealed increased expression of collagen-related genes and proteins with prolonged treatment. This effect was particularly evident in dermal fibroblasts, which play a crucial role in maintaining skin structure and elasticity.
Additionally, spatial transcriptomic data indicated a reduction in senescence-associated secretory phenotype (SASP) factors and inflammatory biomarkers in keratinocytes over time. These findings suggest that RLS-1496 not only eliminates harmful senescent cells but may also promote tissue regeneration and restore a healthier cellular environment in aging skin.
According to Rubedo’s CEO, Dr. Frederick Beddingfield III, the preliminary results exceeded expectations, especially considering the short duration and limited size of the study. He noted that observing meaningful clinical and biomarker changes in a Phase I dermatology trial is uncommon, making these findings particularly encouraging. The data support the potential of RLS-1496 as a disease-modifying therapy capable of addressing the underlying causes of chronic inflammatory and aging-related skin conditions.
Further validation of these findings is anticipated through upcoming scientific presentations. The research has been selected for oral presentation at the American Society for Dermatological Research (SID) Annual Meeting scheduled for May 13–16, 2026, in Chicago. Additionally, Dr. Beddingfield is set to lead a panel discussion on aging and skin at the Dermatology Innovation Forum during the American Academy of Dermatology (AAD) Annual Meeting in Denver.
Beyond the completed Phase I trial, Rubedo is actively advancing a second clinical study of RLS-1496. This ongoing Phase 1b/2a trial is evaluating the drug in patients with actinic keratosis, a precancerous skin condition. Conducted in the United States, this study is expected to conclude later this year. Together, the two trials are anticipated to provide comprehensive data from approximately 70 participants, offering deeper insights into the drug’s therapeutic potential across multiple indications.
RLS-1496 is designed as a first-in-class disease-modifying agent that targets GPX4, a key regulator involved in maintaining cellular redox balance. Dysregulation of GPX4 has been linked to the persistence of senescent cells, which contribute to chronic inflammation and tissue dysfunction. By modulating GPX4 activity, RLS-1496 increases the susceptibility of these senescent cells to ferroptosis—a form of programmed cell death driven by oxidative stress.
This mechanism allows the drug to selectively eliminate harmful aging cells while sparing healthy ones. In addition to clearing senescent cells, RLS-1496 is believed to promote a “redox reset” in neighboring cells, helping to restore normal cellular function and reduce chronic inflammation. This dual action positions the therapy as a potentially transformative approach for treating not only skin diseases but also a broader range of age-related and degenerative conditions.
Rubedo’s Chief Scientific Officer and Founder, Dr. Marco Quarta, emphasized the significance of these findings, describing the trial as one of the first comprehensive evaluations of an anti-aging drug targeting pathological cellular aging. He highlighted that the observed clinical efficacy and biomarker changes align with the drug’s intended mechanism and, in some cases, exceeded expectations. He also expressed optimism about the upcoming full dataset and the results from the ongoing actinic keratosis trial.
The development of RLS-1496 is supported by Rubedo’s proprietary AI-driven drug discovery platform, ALEMBIC™, which is designed to identify therapeutic targets within senescent cells and accelerate the creation of selective cell rejuvenation therapies. This platform has enabled the company to advance a new class of treatments aimed at addressing the root causes of aging and chronic disease at the cellular level.
Overall, the preliminary Phase I results for RLS-1496 represent a promising step forward in the field of dermatology and age-related therapeutics. With a strong safety profile, early evidence of efficacy, and a novel mechanism of action, the drug has the potential to redefine treatment approaches for inflammatory skin conditions and beyond. As further clinical data emerge, RLS-1496 may pave the way for a new generation of therapies focused on restoring tissue health by targeting the fundamental biology of aging.
About Rubedo Life Sciences
Rubedo Life Sciences is a clinical-stage biotechnology company developing a portfolio of innovative, selective cell regeneration drugs that target senescent cells that contribute to age-related chronic diseases. The company’s proprietary AI-powered drug discovery platform, ALEMBIC™, is developing first-in-class small molecule drugs that selectively target pathologically senescent cells that play a critical role in the progression of lung, skin, cancer, neurodegeneration, fibrosis, and other chronic diseases. Rubedo’s lead candidate, RLS-1496, is a promising first-in-class disease-modifying GPX4 modulator currently in Phase I clinical trials. Rubedo’s leadership team comprises industry experts and early pioneers from the fields of chemistry, artificial intelligence, longevity science, and life sciences, with experience in drug development and commercialization at large pharmaceutical companies and leading biotechnology firms. The company is headquartered in Mountain View, California, with an office in Milan, Italy.
