Our DARPin® Platform

Solving clinical problems with custom-built biologics based on natural proteins

We are advancing a novel class of protein therapeutics based on our DARPin® platform, which are able to expand the reach of conventional protein and antibody-based approaches.

Our therapeutic multi-DARPin® candidates are built from DARPin® protein modules. These modules are single-domain proteins, one-tenth the size of a full antibody, with a constant framework and a randomized target binding surface. From our large DARPin® module library (1012 individual members) we are able to select binders to any given target with the same affinity and specificity as the best antibodies.

Opening a novel therapeutic design space

DARPin® modules are the building block for multi-DARPin® candidates. Currently up to 6 — and potentially even more — different DARPin® modules can be fused together on the genetic level, connected with any desired peptide linker. This process yields a range of novel architectures not accessible for other protein therapies — we call this the novel therapeutic design space. As the creation of multi-DARPin® candidates is simple and robust, thousands of combinations can be efficiently generated to test for therapeutic designs that solve a given therapeutic problem.

The reason that DARPin® proteins display this structural flexibility lies in their origin. DARPin® proteins are repeat proteins, a family of proteins that naturally have specialized binding domains in a multi-domain context. DARPin® proteins therefore are exquisitely suited to this task.

Robust and validated approach

DARPin® candidates not only allow for differentiated biological activity, they also have ideal therapeutic properties, including very low immunogenic potential, comparable with antibodies, and no off-target effects. Their use has been validated through extensive preclinical studies and clinical trials, involving up to 2,000 patients (1,900 in ophthalmology and 75 in oncology).

DARPin® candidates also display favorable development properties, including low-cost high-yield manufacturing and up to several years of shelf-life at 4°C.

Our ongoing research continues to add specialized functional sub-platforms to our DARPin® library, including half-life engineering with our HSA-DARPin® module, allowing a systemic half-life of around 12 days in humans; directed cell killing via a T cell recruiting CD3 DARPin® module (status: research); and DARPin®-drug conjugates (status: research).