First Patient Dosed with GPX4 Modulator Targeting Pathologic Senescent Cells

The first patient has been dosed with the lead drug candidate RLS-1496 in a single-center, ascending-dose, randomized, double-blind, vehicle-controlled trial, Rubedo Life Sciences, Inc., announced in a press release.

The study marks the first time a glutathione peroxidase (GPX4) modulator has entered Phase 1 clinical trial, the company said. It is designed to assess the safety, tolerability, clinical effects, plasma bioavailability, and pharmacodynamics of topical RLS-1496 in male or female patients 18 years or older with mild to moderate and stable plaque psoriasis. The subjects’ aging skin will also be treated and assessed to see if RLS-1496 can improve biomarkers of aging and reverse the skin age or biological clock. Based on the results of this study, the company said, the trial will potentially expand to additional inflammatory skin conditions and autoimmune disorders, including but not limited to atopic dermatitis, vitiligo, rosacea, alopecia areata, and scleroderma. A systemic formulation of RLS-1496 is planned to enter Phase 1 clinical trials in 2026.

“We are excited to reach this important milestone not only for our lead candidate RLS-1496 but also for the advancement of longevity science,” Rubedo CEO Frederick Beddingfield, III, MD, PhD, FAAD, FACMS, said in the press release. “As the first company to treat patients with a GPX4 modulator targeting senescent cells in a data-rich Phase 1 clinical trial, we look forward to assessing its potential disease-altering effects on inflammatory skin conditions and skin aging, driving our pipeline forward in line with our goal of making a meaningful impact on age-related diseases and conditions, such as obesity and pain.”

Rubedo is an AI-driven, clinical-stage biotech focused on discovering and rapidly developing selective cellular rejuvenation medicines targeting aging cells.

“For the last decade, longevity scientists have been working to develop a compound ready for human trials that safely and effectively targets pathologic senescent cells,” Rubedo Chief Scientific Officer Marco Quarta, PhD, said in the release. “We are proud that our team developed RLS-1496 into a topical drug candidate in less than 3 years from initiation—two times faster than the industry average via ALEMBIC™, our proprietary AI-driven drug discovery platform with SenTeCh™ chemistry technology. The other candidates in our pipeline are following similar expedited timelines, including systemic RLS-1496, which is aimed to begin Phase 1 clinical trials in 2026.”

The design of the clinical trial is to assess primary and secondary objectives of safety and clinical effects of single and multiple doses of topical RLS-1496, compared to vehicle (control), in patients with mild to moderate stable plaque psoriasis. A key secondary objective is to evaluate the effects of RLS-1496 on target psoriasis lesions using a common measure of psoriasis severity, the modified Investigator’s Global Assessment (mIGA), to evaluate improvement. The trial will be conducted at a single center in the Netherlands with approximately 24 enrolled patients, starting with single-dose application followed by a multidose protocol.

The design of the trial was developed with key insights provided by Rubedo’s Clinical Advisory Board (CAB), which is led by Rubedo Chief Medical Officer and dermatologist Mary Spellman, MD. The CAB includes the following leading dermatologists who are both practicing clinicians and researchers, and are supporting Rubedo as strategic and scientific consultants and advisors:

• Mark Lebwohl, MD, Professor & Chairman Emeritus of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, NY
• Ted Lain, MD, MBA, Executive Director & Principal Investigator, Austin Institute for Clinical Research; CMO, Sanova Dermatology, Austin, TX
• Zoe Draelos, MD, Founder, Dermatology Consulting Services, High Point, NC
• Chris Griffiths, OBE MD FRCP, Emeritus Professor of Dermatology, University of Manchester; Adjunct Professor of Dermatology, King’s College of London, London, England

“As clinicians, we are excited about the potential use of RLS-1496 as a topical treatment for psoriasis, other chronic inflammatory skin conditions, and skin aging itself,” Dr. Lebwohl said. “As researchers, we are intrigued by RLS-1496 as a potential first-in-class GPX4 modulator that was designed to selectively target inflammaging pathologic senescent cells and surrounding tissues. This is a very important milestone in longevity science, and we are thrilled to be working with the Rubedo team to drive this science forward.”

Rubedo’s lead candidate RLS-1496 is a potential first-in-class, disease-altering GPX4 modulator selectively targeting pathologic senescent “zombie” 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.

GPX4 is a major antioxidant-regulating enzyme that protects cells and tissues from free radical damage and is essential for cell survival. In contrast, GPX4 deficiency is associated with regulated cell death (RCD), especially ferroptosis. In certain pathologic cells, aging is associated with an imbalance in GPX4. By modulating GPX4 to selectively encourage cell death in ferroptosis-sensitive senescent zombie cells, RLS-1496 may be able to clear these cells to not only fight disease, but also support healthy cells to function properly.