Mabylon reveals new allergy antibody mechanism

Mabylon AG, a leader in the discovery and development of human-derived, half-life extended multi-specific antibodies, announced the publication of a new study in Clinical & Experimental Allergy, the official journal of the British Society for Allergy & Clinical Immunology (BSACI).

The study shows that allergen-specific IgG4 antibodies may do more than block allergens and prevent allergic reactions: they can also redirect allergens toward antigen-presenting immune cells and promote tolerance-associated immune responses.

In experiments using cells from peanut-allergic patients in the presence of allergen-specific IgG4 antibodies, allergens were redirected away from B cells and toward myeloid antigen-presenting cells. This was associated with lower levels of type 2 inflammatory cytokines, increased IL-10 and increased regulatory T-cell responses.

In a mouse model of peanut allergy, allergen-specific IgG4 antibodies combined with controlled allergen exposure reduced mast-cell activation, supported endogenous allergen-specific IgG responses and prevented the increase in allergen-specific IgE otherwise observed during oral allergen immunotherapy.

Importantly, the same allergen-redirection mechanism was also observed with birch-specific IgG4 antibodies and the major birch pollen allergen Bet v 1. This supports the relevance of the mechanism beyond peanut allergy and across different allergen classes.

The study was conducted in collaboration with Prof. Dr. R. J. Joost van Neerven of Wageningen University & Research.

“Our antibodies are designed to neutralize allergens before they can trigger the allergic cascade. These new data show that they may also actively shape the immune response toward greater tolerance,” said Dr. Niccolò Pengo, Chief Scientific Officer of Mabylon AG. “This gives us a strong rationale to investigate both immediate protection and disease-modifying effects in our clinical programs.”

Mabylon’s platform combines human antibody discovery, identification of disease-relevant allergenic epitopes and leading-edge capabilities in multispecific antibody engineering. Its lead program, MY006, is in an ongoing Phase I clinical study in peanut allergy, with the patient part of the trial underway. MY010, a trispecific antibody targeting birch, oak, and related tree-pollen allergens, has entered GMP manufacturing, with clinical trials expected to start in 2027. Mabylon plans to monitor markers of disease modification in both programs.

“The significance of this work goes beyond a single allergy indication,” said Dr. Alcide Barberis, Chief Executive Officer of Mabylon AG. “It strengthens the biological rationale behind our allergen-neutralization platform and complements our antibody discovery and engineering capabilities. Our primary goal is to develop long-acting therapies that provide rapid protection. These findings suggest that this could potentially be complemented by modification of the underlying allergic immune response over time.”

The authors note that the current findings are based on ex vivo human-cell experiments and an in vivo mouse model. Clinical studies will determine whether the tolerance-associated immune effects translate into durable disease modification in patients.