BM4SIT · AN INNOVATIVE CAUSAL THERAPY FOR ALLERGY: SAFE AND RAPID INDUCTION OF AN ANTI-INFLAMMATORY IMMUNE RESPONSE USING A MUTANT HYPOALLERGEN AND VITAMIN D3

Allergy is the most prevalent chronic inflammatory disease, having great socio-economic impact. Chronic lifelong dependency on symptomatic drugs is an expensive reality for the vast majority of allergy sufferers. Allergen-specific immunotherapy is the only causal and effective treatment targeting the underlying immune mechanism in a more cost-effective way. Yet, long treatment duration and risk of anaphylactic side-effects have prevented this treatment from becoming the first choice. BM4SIT aims at providing an escape from its current niche position by making the treatment safer, more effective and patient friendlier, i.e. developing a therapywith negligible side-effects but improved efficacy, achieved by less injections. The concept of BM4SIT is based on two innovations: replacing current natural allergen extracts by mutated recombinant allergens having been designed to be hypo-allergenic but hyper-immunogenic, and adding an adjuvant to support rapid and effective induction of an anti-inflammatory immune response. The allergen derivative chosen to bring this concept from bench to bedside is BM41, a mutant of the culprit allergen of birch pollen allergy, Bet v 1. Pre-clinical data have demonstrated strongly reduced allergenicity, significantly increased immunogenicity and efficacy in a mouse model for birch pollen allergy. The selected adjuvant is vitamin D3, which has been shown to promote active suppression of inflammation, both in vitro and in a mouse model. The product-focused, IP-protected consortium of BM4SIT will test the immunological and clinical added value of vitamin D3in combination with a current product in a randomized DBPC trial. First-in-man safety of BM41 will be evaluated against placebo, using a current product as comparator. Preliminary efficacy data will be obtained using surrogate in vitro serological and cellular tests.