Duocalin Technology
Pieris AG's proprietary Duocalin technology has successfully demonstrated dual targeting potential.
Commenting on this development, Dr Andreas Hohlbaum, Director of Science and Preclinical Development of Pieris said: "As Pieris continues to validate the therapeutic application of its technologies, dual targeting is viewed as a major step forward. Combining the benefits of bivalent, avid binding of disease targets with the ability to modulate two targets at once shows the clear development potential of the Duocalin technology to treat multi-factorial diseases".
Using individual monomeric Anticalins selected to have picomolar binding affinity to distinct determinants on two defined clinicallyvalidated targets, Pieris has constructed Duocalins as monomeric, bivalent binding proteins that retain target specificity and affinity regardless of the structural orientation of their binding domains. Furthermore, the high intrinsic stability of Duocalins is comparable to monomeric Anticalins, offering flexible formulation and delivery potential for Duocalin-based drug candidates.
Despite the low molecular weight of monomeric Anticalins relative to antibodies, their core scaffold provides a highly selective binding site with high structural plasticity and an extensive binding surface comparable to that achieved with antibodies. The adaptability of the Anticalin scaffold has already allowed Pieris to develop therapeutic and diagnostic product candidates with custom designed functionality. Duocalins allowmultiple targets to be bound and modulated through a single molecule, which is particularly advantageous in diseases known to involve more than a single causative factor. Moreover, bi- or multivalent binding formats such as Duocalins have significant potential in targeting cell surface molecules in disease, mediating agonistic effects on signal transduction pathways or inducing enhanced internalization effects via binding and clustering of cell surface receptors.
Anticalins are derived from the lipocalin scaffold, originally developed by Prof. Dr. Arne Skerra, a leading expert in the field and Headof the Department of Biological Chemistry at the Technical University of Munich, Germany. As engineered human proteins, Anticalins have prescribed binding properties with fundamental similarities to fully human antibodies e.g. picomolar potency and expected low immunogenicity. Anticalins have several additional advantages over conventional antibodies due to their small size (20 kDa), robust tertiary structure and straight composition that confer high solubility, predictable stability and bacterial manufacturability. Fast pharmaco-kinetics and favorable tissue penetration of Anticalins can be balanced through adjustable modulation of serum half-life.
Pieris and its collaborators are not only able to develop superior biotherapeutics, but they also have the ability to overcome the encumbering patent landscape as currently present for the development of conventional antibodies.
Pieris can format Anticalin leads as dual targeting proteins, so-called Duocalins. A Duocalin binds two separate therapeutic targets in one easily produced protein using standard manufacturing processes. Duocalins will create new market opportunities by offering novel therapeutic rationales, better efficacy and increased patient coverage.