Development of MedON for atopic dermatitis

Purpose and goal

Scientists in the MedON consortium have recently discovered an oligonucleotide (MedON-01) that is able to dampen pro-inflammatory responses in vitro in human cells and in vivo in macaques (intranasal and skin). The main purpose of SWElife stage 1 was to demonstrate pre-clinical proof-of-concept of MedON-01 in relevant clinical disease (atopic dermatitis (AD)), conduct predictive therapeutic biomarker analyses and evaluate an easily accessible formulation in vivo as well as business development.

Expected results and effects

Principal component analyses (PCA) of RNA isolated from skin biopsies from lesions concluded that there is large donor variability, supporting the concept that AD is a heterogeneous disease. We further provide evidence that MedON-01 inhibits TLR3 activation (read out CXCL10) in the AD skin explant model and show proof-of-principle of anti-itch effects in mice using a cream formulation. Furthermore, we show that MedON-01 inhibits human skin mast cell degranulation in vitro providing an explanation for anti-itch effects supporting further development as an anti-itch medication.

Planned approach and implementation

The project was organized in three work packages, WP1 validation of MedON-01 in explant skin biopsies from patients, WP2 proof-of-principle in mice, including evaluation of a formulation, WP3 business development and securing IP. We conclude that extensive progress were made in all WPs and that the organization was suitiable for SWElife stage 1 (12 months). An extended network of collaborators were built and the consortia seeks funding for pre-clinical development with a human ex vivo skin model, GMP production of API and formulation, phase 1/2a clinical studies in adult AD patients.