Transforming a Skin Sensitizer to a NON-Skin Sensitizer
Sytheon/Symbionyx researchers published a paper – “A sensitization-free dimethyl fumarate (DMF) pro-drug, isosorbide di-(methyl fumarate) (IDMF), provides a topical treatment candidate for psoriasis” in JID Innovations, 2021; https://doi.org/10/10106/j.xjidi.2021.100040
Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. Its potential, however, has been limited by contact dermatitis that prohibits topical application. IDMF is designed to have similar or better bioactivity as Dimethyl Fumarate (DMF) but with no skin sensitizing side effects of DMF, thus allowing it to be administered orally and topically. After oral administration, it is converted to its active metabolite Monomethyl Fumarate (MMF) by a two-step process – fast release of MMF followed by unique slow release of the second MMF. IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is non-irritating and non-sensitizing in animal models (rat, rabbit, guinea pig). IDMF shares mechanistic pathways similar to DMF, but also has unique IDMF-specific pathways.
Most new anti-psoriatic actives have focused on immunomodulation, IDMF, however, has a unique pleiotropic mechanism that involves dual anti-inflammatory (anti-IL-17A/TNF-α) and antioxidant (NRF-2/ARE) effects with barrier building function. Microarray analysis of cytokine-stimulated keratinocytes showed that IDMF represses the expression of genes specifically up-regulated in psoriatic skin lesions but not those of other skin diseases. In imiquimod-treated mice, IDMF reduced erythema and scaling while repressing the expression of immune response genes in psoriasiform lesions elicited by topical application of IDMF.
Defining the mechanism of IDMF, demonstrating its potential superiority over DMF, and having secured broad patent coverage (US 9,636,321; EP 3273951 B1& multiple pending patents), Sytheon stakes claim through its sister company, Symbionyx Pharmaceuticals Inc., to delve into psoriasis treatment market through partnership.