Rubedo Life Sciences Reports Phase 1b Data Showing Reduced Skin Epigenetic Age and Inflammatory Biomarkers With RLS-1496
Rubedo Life Sciences, a clinical-stage biotechnology company developing therapeutics designed to rejuvenate cellular functions disrupted by aging, has announced new clinical findings for RLS-1496, its lead investigational glutathione peroxidase 4 (GPX4) modulator. The latest Phase 1b findings in patients with atopic dermatitis showed a statistically significant reduction in measured skin epigenetic age following four weeks of topical treatment, alongside changes in molecular markers associated with cellular aging, inflammation and tissue structure.
The company also reported additional Phase 1b/2a clinical data from its RLS-1496 program in patients with actinic keratosis (AK). These findings provide further evidence supporting Rubedo’s proprietary SenoAdaptive approach, which is designed to selectively eliminate pathological senescent cells while helping restore cellular function through redox modulation.
The atopic dermatitis findings were presented at the Aging Research and Drug Discovery (ARDD) conference in Boston on October 2, while the actinic keratosis results were presented in a late-breaking presentation at the 2026 European Academy of Dermatology and Venereology (EADV) Congress in Vienna, Austria, on the same day.
In the atopic dermatitis study, an independent laboratory’s epigenetic clock analysis showed a mean reduction of 2.1 years in measured skin epigenetic age across 11 paired photoaged skin samples after four weeks of treatment. The change, measured using the MitraBio aging clock, was statistically significant, with a reported p-value of 0.032. Individual participants showed reductions of up to eight years at Day 36, while one best responder demonstrated a reduction of 11.7 years at Day 63, approximately one month after treatment ended.
Additional analyses identified changes in DNA methylation patterns associated with aging, molecular evidence of reduced senescence-associated signatures and inflammatory signaling, and improvements in extracellular matrix biology. Histological analysis also showed a 10% increase in type III collagen fibers.
Blood proteomics analyses indicated reductions in circulating inflammatory biomarkers following topical treatment. These changes were observed despite RLS-1496 being undetectable systemically in the majority of study participants, providing preliminary evidence that local GPX4 modulation may influence systemic inflammatory pathways.
The separate actinic keratosis program provided additional support for the compound’s proposed dual mechanism. Rubedo reported GPX4 target engagement in patient skin biopsies, changes in oxidative stress response pathways in non-senescent cells, and reductions in inflammatory and immune signaling associated with cellular senescence. Final clinical results also showed a mean 49% reduction in actinic keratosis lesions across all 22 patients after 28 days of treatment, improving on the previously reported interim reduction of 46%.
Rubedo said RLS-1496 was well tolerated in the actinic keratosis study, with minimal to no irritation observed in treated patients. The company also plans to initiate a Phase 2a study of RLS-1496 in androgenetic alopecia in October.
Phase 1b Atopic Dermatitis Findings Show a Reduction in Measured Skin Epigenetic Age
The Phase 1b atopic dermatitis study evaluated the effects of topical RLS-1496 on photoaged skin in patients with the condition. Among the findings highlighted by Rubedo was a reduction in measured skin epigenetic age, assessed through DNA methylation patterns using an epigenetic clock developed to estimate biological aging.
Epigenetic clocks use patterns of chemical modifications to DNA, including DNA methylation, to estimate biological age. These estimates are distinct from chronological age, which reflects the time that has elapsed since birth. Changes in an epigenetic clock can provide information about biological processes associated with aging, but they do not independently establish that a treatment has reversed aging across the body or improved long-term clinical outcomes.
In the RLS-1496 study, an independent laboratory analyzed 11 paired skin samples collected at baseline and Day 36. The mean difference in measured epigenetic age between the two time points was -2.1 years, with a reported p-value of 0.032.
The statistical significance indicates that the observed change met the study’s reported statistical threshold. However, the result should be interpreted in the context of the small number of paired samples and the specific skin tissue and measurement method used.
Individual responses varied. Rubedo reported reductions of up to eight years in measured epigenetic age at Day 36. In one best responder, the measured reduction reached 11.7 years at Day 63, approximately one month after treatment had ended.
The Day 63 finding is notable because it suggests that a change in the measured epigenetic marker remained evident beyond the four-week treatment period in that individual. Nevertheless, a single best-responder result does not establish that a similar magnitude or duration of response will occur across a broader patient population. Additional studies will be needed to determine the reproducibility, durability and clinical significance of these observations.
The company also reported DNA methylation changes that moved in the opposite direction from patterns associated with skin aging. Further molecular analyses identified enrichment of pathways in hypermethylated regions at Day 63 compared with baseline. These included pathways associated with cellular senescence, cellular stress responses and redox regulation.
Together, the results provide preliminary evidence that pharmacological modulation of GPX4 may influence molecular signatures associated with biological aging in human skin. Rubedo is investigating whether these changes are connected to the company’s broader therapeutic hypothesis: that targeting pathological cellular senescence while supporting the function of stressed cells may offer a new approach to age-related disease.
Molecular Analyses Identify Changes in Senescence, Inflammation and Tissue Structure
In addition to epigenetic clock measurements, Rubedo evaluated skin biopsy samples for molecular and tissue-level changes following treatment with RLS-1496.
The analyses identified reduced senescence-associated molecular signatures and inflammatory signaling, alongside improvements in extracellular matrix biology. The extracellular matrix is the network of proteins and other components surrounding cells that helps provide structural support to tissues. Its composition and organization are important to skin integrity and function.
Collagen is a major component of the skin’s extracellular matrix. It contributes to the tissue’s structure and mechanical properties, and changes in collagen content and organization are associated with skin aging and tissue remodeling.
Histological analysis of skin samples from the study showed a 10% increase in type III collagen fibers. Type III collagen is one of the collagen types found in skin and other tissues and contributes to the structure of the extracellular matrix.
The observed increase adds a tissue-level measurement to the study’s molecular findings. However, the reported result does not by itself establish the extent of any visible improvement in skin appearance, the duration of the change or its effect on the clinical severity of atopic dermatitis. Further research would be needed to determine whether the biomarker changes translate into meaningful and sustained clinical benefits.
The combined results are relevant to Rubedo’s investigation of cellular aging because they extend beyond a single measurement. The study included epigenetic analyses, molecular assessments of senescence and inflammatory signaling, and histological examination of collagen fibers.
These measurements address different aspects of skin biology. Epigenetic clocks estimate biological age based on DNA methylation patterns, molecular signatures provide information about cellular processes, and histology helps characterize tissue structure. Changes across these measures may offer a broader picture of how a treatment affects the tissue under investigation.
Even so, the findings remain early clinical evidence. Their significance will depend on confirmation in larger studies, as well as further assessment of treatment safety, durability and effects on clinical outcomes.
Blood Proteomics Suggests Potential Effects on Inflammatory Pathways
Rubedo also reported changes in circulating inflammatory biomarkers following topical treatment with RLS-1496. Blood proteomics analyses identified reductions in multiple biomarkers, with CCL22 among the most reduced.
CCL22 is a chemokine involved in immune-cell signaling and has been associated with atopic dermatitis disease severity. Chemokines help regulate the movement and activity of immune cells, making them relevant to the study of inflammatory skin conditions.
The observed reduction in CCL22 and other circulating biomarkers suggests that topical treatment may have effects extending beyond the directly treated skin. According to Rubedo, systemic exposure to RLS-1496 was undetectable in the majority of study participants.
This combination of findings raises the possibility that local modulation of GPX4 could influence systemic inflammatory pathways without measurable systemic exposure to the compound in most participants. However, the data do not establish the mechanism responsible for the biomarker changes, and further studies will be necessary to determine whether the findings are reproducible and clinically meaningful.
The company views these results as potentially relevant beyond dermatology. Inflammation is involved in a broad range of biological processes and diseases, including conditions associated with aging. If the observed effects can be confirmed, GPX4 modulation may warrant further investigation in other areas involving inflammatory signaling.
At this stage, however, the findings are preliminary. Reductions in circulating biomarkers do not independently demonstrate that a treatment will improve a systemic inflammatory disease, and the reported observations do not establish efficacy in indications beyond those studied.
Rubedo Highlights the Potential of Its SenoAdaptive Approach
Frederick Beddingfield, M.D., Ph.D., Chief Executive Officer of Rubedo Life Sciences, said the new findings represent progress in translating research on cellular aging into potential treatments for age-related diseases.
“These findings represent an important milestone in translating the biology of cellular aging into potential therapies for age-related diseases,” Beddingfield said. “In addition to meeting primary clinical endpoints, we demonstrated changes in epigenetic aging markers in a human clinical study alongside evidence of selective senescent cell clearance, restoration of cellular function and reductions in circulating biomarkers of systemic inflammation following topical treatment, despite undetectable systemic exposure in most subjects. These findings reinforce the potential of our SenoAdaptive approach to target underlying disease biology and support its potential application beyond dermatology into immunology and inflammation.”
Rubedo’s SenoAdaptive strategy is designed to address pathological cellular senescence while also supporting the function of stressed, non-senescent cells. Cellular senescence is a state in which cells stop dividing but remain metabolically active. Senescent cells can develop altered patterns of gene expression and release signaling molecules that influence their surrounding tissue.
Although senescence is part of normal biology and can have beneficial roles in certain contexts, the accumulation or persistence of pathological senescent cells has been associated with tissue dysfunction and age-related disease processes. Rubedo’s approach seeks to selectively target these cells while also addressing stress-related changes in neighboring cells.
The company is developing RLS-1496 as a GPX4 modulator within this framework. GPX4 is an enzyme involved in controlling lipid peroxidation and maintaining cellular redox balance. Redox regulation describes processes that help cells manage oxidation and maintain the chemical balance required for normal function.
Rubedo’s proposed mechanism involves selectively eliminating pathological senescent cells through ferroptosis, a form of regulated cell death associated with iron-dependent lipid peroxidation, while promoting restoration of redox balance and cellular function in stressed, non-senescent cells.
The company believes this dual approach may offer a way to address more than one component of age-related tissue dysfunction. The clinical data presented at ARDD and EADV provide preliminary evidence supporting aspects of this hypothesis, although further research is required to confirm the mechanism and establish the relationship between the observed molecular changes and clinical benefit.
Actinic Keratosis Results Support the Proposed Dual Mechanism
In addition to the atopic dermatitis findings, Rubedo presented further clinical and translational data from its Phase 1b/2a study of RLS-1496 in patients with actinic keratosis.
Actinic keratosis is a skin condition characterized by rough or scaly lesions that develop on areas exposed to ultraviolet radiation. It is associated with cumulative sun exposure and can require clinical assessment and treatment because some lesions may progress to squamous cell carcinoma.
At the 2026 EADV Congress, Rubedo reported evidence supporting the proposed dual mechanism of RLS-1496. Clinical and translational analyses demonstrated GPX4 target engagement in patient skin biopsies, indicating that the compound influenced its intended biological target in the studied tissue.
Additional spatial transcriptomic and proteomic analyses identified increased activity of NRF2 and oxidative stress response pathways in non-senescent cells. NRF2 is a transcription factor involved in regulating cellular responses to oxidative stress and the expression of genes associated with cellular defense mechanisms.
The analyses also showed reductions in inflammatory and immune signaling patterns associated with cellular senescence across multiple skin cell populations. These observations are consistent with the company’s hypothesis that RLS-1496 can affect pathological senescent cells while helping restore aspects of cellular function in surrounding tissue.
Spatial transcriptomics can help researchers examine gene-expression patterns in the context of tissue organization, while proteomic analyses provide information about proteins and associated biological pathways. Used together, these methods can help characterize how a candidate medicine influences different cell populations and molecular processes within a tissue.
In this study, the findings offered additional information about the biological activity of RLS-1496 beyond clinical lesion measurements. They support continued investigation of the compound’s proposed effects on senescence, inflammation and redox regulation.
However, molecular evidence of target engagement and changes in signaling pathways does not independently establish the full mechanism of action in patients. Additional studies will be needed to determine how these biological changes relate to clinical outcomes and whether the effects can be reproduced in larger patient populations.
Final Actinic Keratosis Results Show a Mean 49% Reduction in Lesions
Rubedo’s final clinical results from the actinic keratosis program showed a mean 49% reduction in lesions across all 22 patients after 28 days of treatment with RLS-1496. This was an improvement over the previously reported interim mean reduction of 46%.
The updated result provides a clinical measure of the compound’s activity in the study population. Lesion reduction is relevant in actinic keratosis research because the number and characteristics of lesions are among the factors used to assess treatment response.
The reported 49% mean reduction reflects the results across the 22 participants and should not be interpreted as the response achieved by every individual patient. The announcement did not provide further details about response distributions, longer-term follow-up or comparative treatment outcomes.
Rubedo also reported that RLS-1496 was well tolerated, with minimal to no irritation observed in treated patients. Tolerability is an important consideration for topical products because local skin reactions can affect patient comfort and the ability to continue treatment.
The findings offer preliminary support for further evaluation of RLS-1496 in actinic keratosis. Additional clinical development will be needed to clarify the durability of lesion reduction, the treatment’s safety profile and its potential role relative to available management approaches.
Planned Phase 2a Study to Evaluate RLS-1496 in Androgenetic Alopecia
Rubedo plans to initiate a Phase 2a study of RLS-1496 in androgenetic alopecia in October. Androgenetic alopecia is a common form of hair loss influenced by genetic and hormonal factors. The planned study would extend the compound’s clinical investigation into another condition with biological processes that may intersect with tissue aging and cellular function.
The company has not provided further details in the announcement regarding the planned study’s design, participant enrollment, endpoints or expected results.
The planned program nevertheless reflects Rubedo’s interest in exploring whether the biological effects under investigation with RLS-1496 can be applied beyond the initial dermatological indications. The atopic dermatitis and actinic keratosis studies provide early clinical and translational observations that the company intends to use to inform its development strategy.
Early Clinical Findings Support Further Investigation
The latest findings position RLS-1496 as an investigational candidate being evaluated for its potential to influence cellular aging, senescence and inflammatory signaling. In the Phase 1b atopic dermatitis study, four weeks of topical treatment was associated with a statistically significant mean 2.1-year reduction in measured skin epigenetic age across 11 paired samples, alongside changes in DNA methylation, collagen fibers and inflammatory biomarkers.
In the separate actinic keratosis study, Rubedo reported GPX4 target engagement, changes in oxidative stress response pathways, reductions in senescence-associated inflammatory signaling and a mean 49% reduction in lesions across 22 patients after 28 days of treatment.
Together, the results provide early evidence supporting continued investigation of the company’s SenoAdaptive approach. They also illustrate how Rubedo is combining clinical measurements with molecular and tissue-level analyses to evaluate the effects of its investigational medicine.
The findings do not establish that RLS-1496 reverses aging throughout the body or provides proven clinical benefits beyond the conditions studied. Larger and appropriately designed clinical trials will be required to confirm the reported changes, assess durability and safety, and determine whether the biological effects translate into meaningful patient outcomes.
For Rubedo Life Sciences, the next stages of development will help clarify whether modulation of GPX4 can provide a useful therapeutic strategy for pathological cellular senescence and related inflammatory processes. The planned Phase 2a study in androgenetic alopecia will also broaden the clinical investigation of RLS-1496 as the company continues to evaluate its potential across dermatology and other areas associated with cellular aging.
About RLS-1496
RLS-1496 is Rubedo’s lead investigational SenoAdaptive medicine and a first-in-class topical GPX4 modulator designed to selectively target pathological senescent cells while restoring cellular function in stressed, non-senescent cells. The compound was discovered using Rubedo’s proprietary ALEMBIC platform, which integrates artificial intelligence and single-cell multiomics to identify disease-driving senescent cell populations and novel therapeutic targets. RLS-1496 was previously evaluated in Phase 1b and Phase 1b/2a clinical studies across multiple dermatologic indications, including atopic dermatitis, psoriasis, actinic keratosis and photoaged skin.
About Rubedo Life Sciences
Rubedo Life Sciences is a clinical-stage biotechnology company developing a new generation of medicines designed to selectively target pathological senescent cells that contribute to chronic and age-related diseases. Through its proprietary ALEMBIC AI-enabled drug discovery platform, Rubedo identifies disease-driving senescent cell populations and develops targeted SenoAdaptive therapeutics designed to eliminate pathological cells while preserving and restoring healthy cellular function. Its lead program, RLS-1496, is a first-in-class GPX4 modulator in clinical development for dermatologic indications.