D2.496 - First-in-Human Phase I Clinical Outcomes of BxC-I17e Enriched with HSP70/miR-22-3p in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic type 2 inflammatory skin disorder marked by pruritus, barrier dysfunction, and quality-of-life impairment. While targeted therapies improve outcomes, sustained control remains limited by incomplete Th2 pathway suppression and safety constraints. Interferon-γ–primed mesenchymal stem cell–derived extracellular vesicles (BxC-I17e) represent a novel, cell-free immunomodulatory biologic. This study reports first-in-human phase I outcomes and provides mechanistic evidence for BxC-I17e in moderate-to-severe AD.

Adults with moderate-to-severe AD received a single subcutaneous dose of BxC-I17e in a phase I trial. Safety, tolerability, and efficacy were evaluated to Week 8 by Investigator’s Global Assessment (IGA), Eczema Area and Severity Index (EASI), and pruritus Numerical Rating Scale (NRS). Translational studies using 2,4-dinitrochlorobenzene (DNCB)- and house dust mite (HDM)-induced AD mouse models, along with human skin cell systems, showed suppression of Th2 signaling. Proteomic and miRNA profiling defined key BxC-I17e cargo mediating these effects.

BxC-I17e was well tolerated, with no treatment-related adverse events in patients with moderate-to-severe AD. Clinically meaningful improvements were observed through Week 8 (IGA severe 16.7%→0%; EASI severe 33.3%→16.7%; pruritus NRS severe 33.3%→0%). In translational models, BxC-I17e suppressed dermal inflammation, Th2 cytokines, and pruritus-related mediators, accompanied by reduced IL-4Rα/IL-13Rα1 expression and STAT6 activation. Multi-omic profiling identified HSP70 and miR-22-3p as cooperative cargo regulating IL-4Rα/IL-13Rα1 expression, with additional components modulating IL-31Rα/OSMRβ signaling.

A single subcutaneous dose of BxC-I17e showed favorable safety and durable Week-8 improvements in patients with moderate-to-severe AD. Mechanistic and multi-omic data support a receptor-targeted, extracellular vesicle (EV)-based mechanism that suppresses Th2 signaling, providing a translational foundation for further clinical development in AD.