Background

Excess histamine is the main driver of severe allergic diseases such as mastocytosis (orphan disease), mast-cell-activation syndrome (MCAS), asthma, urticaria, atopic dermatitis, and anaphylaxis, and is not adequately addressed by anti-histamines and / or IgE or IL4/7 targeted therapies such as Dupixent and Xolair. Anti-hstamines can only block ~3-5 fold increased histamine plasma concentrations (~5 ng/ml) but during anaphylaxis or MCAS for example mean histamine concentrations increase more than 100-fold. Naturally occurring diamine oxidase is the ideal solution to rapidly and safely degrade histamine, but its short alpha half life of under 4 minutes is insufficient for pharmaceutical development and thus oral and former products on the market were unsuccessful.

Technology Overview

We modified natural human DAO resulting in dramatically improved pharmacokinetic with 95-fold increased half life, but unaffected pharmaco-dynamic properties.

An additional modification inhibits natural tetramerization and higher order aggregate formation. Our modified DAO forms only “natural” dimers, which greatly simplifies protein expression, purification but also lowers immunogenicity and increases safety.

The next steps are generation of a GMP high expression cell line and a suitable GMP manufacturing process, toxicity and Phase 1 studies. Approval under exceptional circumstances (EC) is possible with Phase 1 data (Discussions with EMA during orphan designation scientific advice). Expedited review programs of the FDA are very likely also applicable.

Further Details

Publication

Benefits

First-in-class biopharmaceutical – a modified natural enzyme with strongly improved half-life that enables its development as a therapeutic
Excellent IP position
Safe – naturally occurs in high concentrations during pregnancy
Prevents histamine action on all four receptors - totally histamine receptor independent (incl. H4R relevant for asthma and skin diseases)
Orphan Drug Designation granted by EMA for Mastocytosis
Large indications include asthma or anti-histamine resistant chronic urticaria with high unmet medical need
Much faster acting than Xolair and Dupixent, no drug-related adverse effects expected, naturally occurring enzyme

Applications

Mastocytosis
Mast cell activation syndrome
Chronic urticaria
Atopic Dermatitis
Anaphylaxis
Asthma

Opportunity

Product ready for GMP cell line development and manufacturing.

Available for:

Development partnership
Licence
Investment into spin-off

Pan-Anti-Histamine

Patents

IP Status

Seeking