Rubedo’s RLS-1496 Reduces Actinic Keratosis Pre-Cancerous Skin Lesions by 46% at Four Weeks with Minimal Irritation in Preliminary Results of Phase 1b/2a Study

RLS-1496 is an investigational, first-in-class, disease-modifying, selective glutathione peroxidase 4 (GPX4) modulator that targets pathologic senescent and other stressed, aging cells that drive chronic, age-dependent diseases, such as AK, and represents a novel drug category — Adaptive SenoTherapeutics In recognition of May as Skin Cancer Awareness Month, Rubedo is calling attention to the myths and facts surrounding AKs — and to the urgent need for a new generation of treatments that are effective without the side-effect burden of today's options

Rubedo Life Sciences, Inc. (Rubedo), an AI-driven, clinical-stage biotech focused on selective cellular rejuvenation medicines targeting aging cells, today announced preliminary results from a Phase 1b/2a study of RLS-1496 in patients with actinic keratosis (AK), a common age-related condition resulting in precancerous skin lesions, that is most commonly seen after age 65.¹ The open-label multi-center trial, conducted in the United States, assessed the safety, tolerability, and clinical effects of RLS-1496 1% cream in adult patients with AK on the forearms. RLS-1496 is the first selective glutathione peroxidase 4 (GPX4) modulator to be studied in human trials, and the first targeting cellular rejuvenation as a new therapeutic pathway in a novel category called Adaptive SenoTherapeutics. Interim data from the study were presented at the RBC Capital Markets Global Healthcare Conference in New York City on May 19, 2026.

Preliminary RLS-1496 Actinic Keratosis Trial Results

• The Phase 1b/2a study of RLS-1496 showed a 46% reduction in AK count compared to 11% for untreated control at 4 weeks in the first 18 of 24 patients evaluated
• RLS-1496 was associated with favorable safety, with no serious adverse events (AEs) and no discontinuations due to AEs during the 4-week study
• RLS-1496 was well-tolerated, causing minimal local irritation, an area of high unmet need in the standard of care
• A Phase 2b dose-ranging AK study for RLS-1496 will begin in Q4

“A 46% reduction in AK lesions at four 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 Rubedo CEO Frederick Beddingfield, III, MD, PhD, FAAD, who is also a practicing dermatologist. “AKs are precancerous lesions that lead to squamous cell carcinoma, and patients deserve a therapy that is designed to be both effective and tolerable. We look forward to advancing RLS-1496 for AKs, as well as continuing its development in psoriasis, atopic dermatitis, photo-aging, and other degenerative diseases and conditions associated with the aging process.”

These AK data results follow the preliminary results from Rubedo’s recently completed Phase 1b clinical trial, conducted in the European Union, which assessed the safety, tolerability, clinical effects, plasma bioavailability, and pharmacodynamics of topical RLS-1496. This single-center, ascending-dose, randomized, double-blind, vehicle-controlled trial in patients with plaque psoriasis, atopic dermatitis, and skin aging (photo-aged skin) met its primary safety endpoint, with RLS-1496 also demonstrating early signs of efficacy, including a remarkable 20% decrease in epidermal thickness in psoriasis patients on therapy compared to a 30% increase with patients on vehicle.²

“The preliminary results from this AK trial, coupled with those from our Phase 1 trial in patients with plaque psoriasis, atopic dermatitis, and skin aging, show continued promise for RLS-1496 as the first GPX4 modulator and a new class of Adaptive SenoTherapeutics,” said Rubedo Chief Scientific Officer and Founder Marco Quarta, PhD. “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 to fibrosis, metabolic disease, sarcopenia, and neurodegeneration. What makes RLS-1496 particularly exciting is that it appears to act across several fundamental hallmarks of aging — from cellular senescence to autophagy and oxidative stress imbalance. This is the kind of multi-axis biology we believe will define the next generation of true longevity medicines.”

The data from Rubedo’s RLS-1496 AK trial, as well as data from the Phase 1b trial, including a comprehensive data set of 70 subjects assessing RLS-1496 in aging skin, are being compiled for submission to major medical journals and medical meetings.

Actinic Keratosis: A Common Health Condition with an Unmet Need

It is estimated that 58 million Americans have one or more AKs.³ The U.S. annual market size for AKs was $3.55 billion in 2025, and will grow to $4.8 billion by 2035.⁴ In recognition of Skin Cancer Awareness Month, Rubedo is calling attention to common myths that are believed about AKs and highlighting why new treatments are still urgently needed for the millions of people affected by AKs.

Myth 1: AKs are harmless sun spots and usually go away on their own.

The Facts:

• AKs form as a result of long-term sun exposure, and often appear as small, rough patches of skin that can vary in color. They typically are found on sun-exposed areas of the body, including the face, scalp, neck, arms, and hands.³
• Left untreated, AKs can progress into squamous cell carcinoma (SCC), which is the second most common skin cancer.⁵ An estimated 1.8 million cases of SCC are diagnosed each year,⁶ and it is estimated that 82% of SCCs begin as AKs.⁵

Myth 2: AKs are rare.

The Facts:

• AKs are among the most common diagnoses made by dermatologists, with a global prevalence of approximately 14%.⁷ The prevalence of AK increases with age, frequently developing after age 50 but most commonly seen after age 65.¹
• While a single lesion carries a relatively low risk of progression, the presence of one AK indicates a higher likelihood of developing additional lesions over time, increasing the cumulative risk of skin cancer.³

Myth 3: Current AK treatments are good enough.

The Facts:

• Available treatments — including topical creams, cryosurgery, and photodynamic therapy — can be effective but are often associated with pain, redness, swelling, crusting, or peeling that can take weeks to heal.⁸
• These side effects lead some patients to delay or discontinue treatment, leaving lesions untreated and increasing the risk that AKs progress to skin cancer.⁸ New effective treatment approaches with improved tolerability are needed to protect patients from preventable cancer.

About RLS-1496 and GPX4 Modulation

Rubedo’s lead candidate RLS-1496, being developed for topical and oral administration, is a first-in-class, disease-modifying GPX4 modulator selectively targeting pathologic senescent and other stressed, aging cells that drive chronic, age-dependent diseases. 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 fight disease and 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' through a controlled hormetic response in stressed neighboring cells, effectively clearing the source of chronic inflammation while actively re-establishing healthy tissue homeostasis. This dual-action mechanism represents a novel drug category—Adaptive SenoTherapeutics.

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.

¹ Flohil SC, van der Leest RJT, Dowlatshahi EA, et al. Prevalence of Actinic Keratosis and Its Risk Factors in the General Population: The Rotterdam Study. Journal of Investigative Dermatology, Volume 133, Issue 8, 2013, Pages 1971-1978, https://doi.org/10.1038/jid.2013.134

² Vitari A, Laslavic A, Spellman M, et al. Abstract 0510: Clinical study of RLS-1496 topical cream: Targeting cellular senescence in patients with mild-to-moderate plaque psoriasis. Presented at 2026 Annual Meeting of the Society for Investigative Dermatology (SID). https://www.sidnet.org/wp-content/uploads/2026/05/SID_Chcago26_Abstract_FInal_4.pdf#page=132

³ The Skin Cancer Foundation. Actinic Keratosis Overview. Accessed May 2026. https://www.skincancer.org/skin-cancer-information/actinic-keratosis/

⁴ Nova1Advisor. U.S. Actinic Keratosis Treatment Market Size, Share & Trends Analysis Report By Therapy (Topical/Drugs, Surgery, Photodynamic Therapy), By Drug Class, By Product, By End-use, And Segment) - Industry Analysis, Share, Growth, Regional Outlook and Forecasts, 2026-2035. Accessed May 2026. https://www.novaoneadvisor.com/report/us-actinic-keratosis-treatment-market

⁵ Li Z, Lu F, Zhou F, et al. (2025). From actinic keratosis to cutaneous squamous cell carcinoma: the key pathogenesis and treatments. Frontiers in immunology, 16, 1518633. https://doi.org/10.3389/fimmu.2025.1518633

⁶ The Skin Cancer Foundation. Squamous Cell Carcinoma Overview. Accessed May 2026. https://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma/

⁷ George CD, Lee T, Hollestein LM, et al. Global epidemiology of actinic keratosis in the general population: a systematic review and meta-analysis, British Journal of Dermatology, Volume 190, Issue 4, April 2024, Pages 465–476, https://doi.org/10.1093/bjd/ljad371

⁸ Balcere A, Rone Kupfere M, Čēma I, Krūmiņa A. (2019). Prevalence, Discontinuation Rate, and Risk Factors for Severe Local Site Reactions with Topical Field Treatment Options for Actinic Keratosis of the Face and Scalp. Medicina (Kaunas, Lithuania), 55(4), 92. https://doi.org/10.3390/medicina55040092

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