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

(BUSINESS WIRE) -- Rubedo Life Sciences, Inc. (Rubedo), an AI-driven, clinical-stage biotech focused on discovering and rapidly developing selective cellular rejuvenation medicines targeting aging cells, today announced preliminary results from a single-center, ascending-dose, randomized, double-blind, vehicle-controlled trial in patients with plaque psoriasis, atopic dermatitis, and skin aging (photo-aged skin). The recently completed Phase 1 clinical trial, conducted in the European Union, was designed to assess the safety, tolerability, clinical effects, plasma bioavailability, and pharmacodynamics of topical RLS-1496—the first-ever GPX4 (selective glutathione peroxidase 4) modulator to be studied in human trials, and the first specifically targeting cellular rejuvenation, an area of great interest to the scientific community as a new therapeutic pathway. The study met its primary endpoint, with RLS-1496 also demonstrating early signs of efficacy.

Preliminary Trial Results

• RLS-1496 was well-tolerated, with no serious adverse events (AEs) and no discontinuations due to AEs or tolerability issues during the 4-week study

• In psoriasis patients:

  • Clear dose-response seen during the trial (0.1%, 0.5%, and 1.0%); all doses were well-tolerated so only 1.0% dose will be evaluated moving forward

  • Dose-related target engagement of RLS-1496 and GPX4

  • Overall reduction in senescent cells seen with RLS-1496 in the mid- and high-dose cohorts

  • Some subjects treated with RLS-1496 had a reduction of senescent cells, which was associated with a reduction of inflammatory cytokines such as IL-19 and S100A7; this reduction was not seen in the vehicle cohort

  • An average 20% reduction in epidermal thickness was observed on histology in subjects treated with RLS-1496 for one month

  • A statistically significant relationship was seen between target engagement and improvement in clinical psoriasis severity

• In atopic dermatitis patients:

  • Even higher levels of target engagement and substantial clinical improvement were seen in atopic dermatitis subjects on RLS-1496

  • After one month of treatment, 25% of subjects on RLS-1496 had a >/=4-point change in pruritus (or itching) on the numeric rating scale (NRS); no vehicle subjects had a 4-point or more change on the NRS

• Early photo-aging data show:

  • Dose-dependent target engagement in non-lesional photo-aged skin

  • Histology, proteomics, and spatial transcriptomics indicate that collagen gene and protein expression increase with treatments over time, in particular, spatial transcriptomics shows an effect in dermal fibroblasts

  • Spatial transcriptomics show indication that SASPs and inflammatory biomarkers decrease with treatments over time in keratinocytes

“We’re pleased by the positive safety and tolerability seen in the trial, with the additional preliminary results exceeding our expectations by showing very promising and clinically meaningful results across multiple measures including histologic, cellular, biomarker, and clinical evaluations in psoriasis, atopic dermatitis, and photo-aged skin,” said Rubedo CEO Frederick Beddingfield, III, MD, PhD, FAAD. “It’s uncommon to see clinical effect in a Phase 1 dermatology study given the shorter study duration and smaller sample size, and we are excited by the potential of this treatment with the clinical and biomarker changes we have observed already.”

Dr. Beddingfield will preview these results during a panel he will moderate on senescence and skin at the Dermatology Innovation Forum (DIF) during the American Academy of Dermatology annual meeting on Thursday, March 26, at 1:05 pm MT in Denver. Additional results from this trial will be presented during an oral presentation at the Society for Investigative Dermatology (SID) from May 13-16, 2026, in Chicago.

A second study for RLS-1496 – a Phase 1b/2a study in actinic keratosis (precancerous skin lesions) – is underway in the United States with completion expected later this year. In both trials, all subjects have their photo-aged skin treated with RLS-1496 in addition to their lesional skin relating to their medical condition. From these trials, Rubedo expects to obtain a large dataset on the treatment of aging skin from approximately 70 subjects.

Rubedo Chief Scientific Officer and Founder Marco Quarta, PhD, said, “This is one of the first comprehensively evaluated trials of a senotherapeutic drug that targets aging pathologic cells and regenerates healthy cells, and also the first human trial of a GPX4 modulator. These preliminary results show the drug working mechanistically as expected and even better than should be expected clinically in a 4-week trial. We are excited for the upcoming comprehensive results from this trial, as well as the results of the ongoing trial in actinic keratosis.”

About RLS-1496 and GPX4 Modulation

Rubedo’s lead candidate RLS-1496, being developed for topical and oral administration, is a potential first-in-class, disease-modifying GPX4 modulator selectively targeting pathologic senescent or “aged” cells that drive chronic degenerative diseases and conditions associated with biological aging processes. These include immunology and inflammation (I&I), dermatology and skin aging, metabolic syndrome (obesity, diabetes, liver fibrosis), sarcopenia, and neurodegenerative disease.

In certain pathologic cells, aging is associated with an imbalance in GPX4. Modulation of GPX4 sensitizes cells to ferroptosis, which is a type of programmed cell death and is believed to be an Achilles heel of senescent cells. By modulating GPX4 in ferroptosis-sensitive senescent “aged” cells, RLS-1496 may be able to clear these cells to not only fight disease, but also support healthy cells to function properly and restore tissue homeostasis. Beyond its targeted senolytic function in triggering selective ferroptosis within pathological senescent cells, RLS-1496 could also act as a restorative modulator that induces a vital 'redox-reset' in stressed neighboring cells, effectively clearing the source of chronic inflammation while actively re-establishing healthy tissue homeostasis.

RLS-1496 uses Rubedo’s proprietary, AI-driven drug discovery platform ALEMBIC™, which identifies targets within pathologic senescent cells and develops selective cellular rejuvenation medicines for these targets.

About Rubedo Life Sciences

Rubedo Life Sciences is a clinical-stage biotech developing a broad portfolio of innovative selective cellular rejuvenation medicines targeting aging cells that drive chronic age-related diseases. Our proprietary AI-driven ALEMBIC™ drug discovery platform is developing novel first-in-class small molecules to selectively target pathologic and senescent cells, which play a key role in the progression of pulmonary, dermatological, oncological, neurodegenerative, fibrotic, and other chronic disorders. Our lead drug candidate – RLS-1496, a potential first-in-class disease-modifying GPX4 modulator – is currently in Phase I clinical trials. The Rubedo leadership team is composed of industry leaders and early pioneers in chemistry, AI technology, longevity science, and life sciences, with expertise in drug development and commercialization from both large pharmaceutical and leading biotechnology companies. The company is headquartered in Mountain View, CA, USA, and has offices in Milan, Italy. For additional information, visit www.rubedolife.com.

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