A Novel TORC1 Inhibitor, RLX ‐201, Improves Skin Health, Biomechanics, and Extracellular Matrix Integrity in a Double‐Blind Clinical Study

ABSTRACT Background Skin aging is characterized by decline in structural integrity, extracellular matrix (ECM) organization, and biomechanical function. Emerging concepts in skin longevity emphasize preservation of tissue resilience through modulation of aging pathways, including mechanistic target of rapamycin complex 1 (TORC1), a central regulator of the 12 currently accepted hallmarks of aging. Aim Evaluate the effect of topical formulations containing RLX‐201 on clinical photoaging, skin biomechanics, and molecular biomarkers. Methods In this 12‐week, randomized, double‐blind, vehicle‐controlled study, female subjects with moderate‐to‐severe facial photoaging applied RLX‐201 formulation or vehicle twice daily. Clinical assessments were performed at baseline and Weeks 2, 4, 8, and 12 by an investigator. Skin viscoelastic properties were quantified using elastometry. Subject self‐assessments were collected. Mechanistic evaluation was conducted in 3D full‐thickness skin tissue models, assessing phosphorylation of ribosomal protein S6 (pRPS6) as a surrogate marker of mTORC1 activity. Results Treatment with RLX‐201 resulted in significant improvements in clinical parameters of skin firmness, elasticity, sagging, and overall skin quality compared with vehicle ( p ≤ 0.05), with onset observed as early as Week 2 and sustained through Week 12. Biomechanical analysis demonstrated significant enhancement in viscoelastic properties. Subject‐reported outcomes showed high concordance with investigator assessments, with > 85% of participants reporting improvements in radiance, texture, and hydration. Tissue analysis demonstrated suppression of TORC1 activity, with ~91% reduction in pRPS6 expression. Conclusions Topical modulation of TORC1 improves clinical, biomechanical, and molecular features of skin aging. These findings support a mechanistic approach to enhancing skin health, in which targeting nutrient‐sensing pathways enhances tissue resilience and functional performance, extending beyond conventional cosmetic outcomes.