Trimerbodies have the potential to become next-generation drugs with enhanced potency, efficacy and improved safety profiles as compared to existing targeted biologic drugs. Because of the stable modular structure, small size, and human origin, the Trimerbody format has several anticipated advantages over other therapeutic protein drugs:
Safety: Trimerbodies have been non-immunogenic and well-tolerated in preclinical studies. Additionally, they do not carry the Fc region, which has been implicated in some instances where the infusion of therapeutic antibodies led to cytokine storm syndrome and extremely adverse health effects.
Effectiveness: The Trimerbody format can be designed to yield antibodies with high degrees of multivalence and multispecificity, due to the inclusion of up to six binding domains per Trimerbody. Sustained binding due to simultaneous multiple target interactions (multivalence) improves the strength of binding of an interaction by lowering the rate of dissociation of an antibody from its target; this can increase the efficacy of therapeutics with many different mechanisms of action. Multispecificity can be used to target multiple antigens in order to avoid resistance and recurrence; multivalence facilitates this by ensuring that the efficacy will be sufficiently high even against cells down-regulating target antigens. Trimerbodies also have the potential for agonistic receptor cross-linking activity due to their multivalent structure, which enables certain therapeutic mechanisms of action such as T cell costimulatory immunotherapy.
Flexible formatting: The modularity of the Trimerbodies allows for a diverse range of protein domains to be considered, including homing peptides, receptor or ligand domains, cytokines, Fc domains, and binding domains (scFvs, sdAbs, and antibody mimetics). In conjunction with MT, TT or ATTACK technology, a tightly controlled antibody can be designed with the desired specificities and valences. Due to their small size and stable structure, Trimerbodies open up a huge potential to expand various therapeutic modalities, including the recruitment of T cell effector functions.
Speed, robustness & low manufacturing costs: Trimerbodies can rapidly be advanced from discovery into development through highly standardized screening, characterization and optimization techniques. They can be produced and purified at comparably low cost of goods based on mammalian, bacterial, insect and yeast expression technologies.