Immunology

NuGel is a topical formulation of HY209, an inhibitor of the NLRP3 inflammasome that acts by modulating the GPCR19-P2X7R pathway. In atopic dermatitis animal models, NuGel demonstrated efficacy comparable to that of steroid treatments by suppressing inflammatory cytokines such as TNF-α, IL-1β, IL-6, and RANTES. Following confirmation of its safety and efficacy in domestic Phase 1 and Phase 2a clinical trials, a global Phase 2b clinical trial is currently underway in both the United States and South Korea.

In the DNCB-induced atopic dermatitis animal model, NuGel showed superior skin regeneration effects in healing atopic skin lesions compared to the standard steroid treatment, Eucrisa (a PDE4 inhibitor and the first approved atopic dermatitis drug in 15 years), and tofacitinib (a JAK inhibitor under development as a representative anti-inflammatory drug). Histological analysis also confirmed NuGel's excellent ability to restore the skin to a normal state.

NuGel significantly reduced the infiltration of inflammatory cells such as mast cells, eosinophils, and MPO in atopic skin lesions. Moreover, it increased the expression of regulatory T cells and the anti-inflammatory cytokine IL-10, suggesting not only direct suppression of inflammatory cytokine production but also indirect modulation of both innate and adaptive immunity, leading to faster alleviation of atopic dermatitis symptoms.

In the ongoing U.S. trial, titled "A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2b Study in Patients with Mild to Moderate Atopic Dermatitis," Part 1, aimed at determining the optimal dose to demonstrate efficacy, was completed in January 2025. The Safety Monitoring Committee recommended continuation of the study based on the favorable safety profile. No serious adverse events were reported during the 8-week topical application of NuGel, and all adverse drug reactions (ADRs) related to the study drug were mild, confirming NuGel's superior safety compared to placebo. Part 2 of the Phase 2b trial is currently enrolling subjects, with the goal of completing registration within 2025.

Notably, in a world-first approach to atopic dermatitis treatment, Shaperon has integrated precision medicine by developing its own biomarker that can predict therapeutic response to NuGel. A patent application for this biomarker was filed at the end of 2022.