What are DARPin®therapeutics?
DARPins® therapeutics are a new class of small protein therapeutic agents derived from natural ankyrin repeat proteins, one of the most common binding proteins in nature and responsible for diverse functions, such as cell signaling and receptor binding.
Our DARPin® therapies are built around our mono-DARPin® proteins, which are robust and potent proteins that bind to a single specific target. DARPin® proteins can treat a single validated disease pathway (mono-DARPin® therapy) or efficiently combine two or more mono-DARPin® proteins to form multi-DARPin® proteins that bind to multiple targets (or multiple epitopes/sites on a single target) without changing the fundamental attributes of the mono-DARPin® proteins.
Due to their small size, high potency, high stability, high affinity (strong binding) and flexible architecture, we believe that DARPin® therapeutic products have the potential to overcome many of the limitations that conventional and other therapeutic approaches face when addressing complex diseases, such as cancer. Conventional therapeutic approaches typically target a single disease pathway, which can result in limited efficacy. The complexity of a disease often results from the disruption of multiple pathways in parallel or sequentially. We are able to use our DARPin® technology to rapidly generate thousands of different multi-DARPin® proteins, which may also include non-DARPin® elements, such as a toxin. The diversity of formats and robustness of these multi-DARPin® proteins enables us to employ an empirical approach (outcome-based screening) to efficiently identify those DARPin® proteins that have great potential to overcome limitations of current therapeutic approaches for the chosen disease.
This flexible, agile and cost-efficient drug-development approach can help us speed up the development of DARPin® therapeutic products while de-risking the process with our validated methods of differentiation and identification.
An example of a multi-benefit DARPin® product is the multi-VEGF/PDGF DARPin® protein we are developing in partnership with Allergan, which combines treatment for both anti-PDGF and anti-VEGF in a single molecule, as opposed to the current standard of care, Lucentis®, which is solely an anti-VEGF treatment. VEGF and PDGF are the two most common and critical pathways implicated in serious retinal diseases.
Development of DARPin® therapeutics
The Origin of the DARPin® Technology
The Molecular Partners story begins with the scientific discovery of our unique DARPin® technology. Our founders worked together as PhD students and post-docs in the biochemistry department at the University of Zurich under the supervision of Prof. Dr. Andreas Plückthun. There, they created a new class of small-protein therapies as an expansion over conventional antibody approaches. Recognizing the significant potential of DARPin® therapies for patients, they incorporated Molecular Partners in 2004.
Architecture of DARPin® therapeutics
How do DARPin® therapeutics work?
To identify and differentiate DARPin® therapeutics for complex disease, Molecular Partners first directly measures the activity of our multi-DARPin® proteins against a set of particular biological functions (such as in a cellular assays and/or disease models) to identify which multi-DARPin® proteins have the effect we are looking for. The resulting potential therapeutic effects of the identified multi-DARPin® proteins often include a functionality that we believe goes a dimension beyond what monoclonal antibodies and other protein therapies can currently do. These multi-benefit DARPin® products can target multiple pathways (i.e. linked mono-DARPin® proteins that target multiple pathways), resulting in a stronger therapeutic effect as compared to therapies targeting a single pathway, or targeting a single pathway using a novel mechanism of action (e.g. by targeting multiple epitopes on a single target).
Benefits of DARPin® therapeutics
What sets DARPin® therapeutics apart from competitors, including other protein therapies or monoclonal antibodies?
While protein therapies such as antibodies and natural proteins have changed medicine, they are usually designed to treat only one disease target. In contrast, multi-benefit DARPin® therapeutics function as a team. Instead of just one treatment for a complex disease, we can bring together multiple small proteins with high specificity and potency to inhibit multiple disease-specific targets in a single medicine. These characteristics make DARPin® proteins ideal agonistic, antagonistic or inhibitory drug candidates.
|Small size||14 – 18 kD||a increased tissue penetration|
|High potency||< 5 – 100 pM||active at low concentration|
|High stability and solubility||soluble at > 100 g/L||ideal drug properties|
|Cost efficient bacterial production||7 – 15 g/L||rapid and low-cost|
|Tunable PK properties||PK toolbox (min – weeks)||adjust to patient need|
|High developability||robust class behavior||standard processes|
The manufacturing process for DARPin® products is less complex and more efficient than current monoclonal antibody approaches. All formats of DARPin® proteins can be manufactured to cGMP standard high-yield bacterial fermentation and are easily formulated.
Furthermore, DARPin® product candidates can be engineered to include other non-DARPin® treatments in a wide variety of formats. Molecular Partners is advancing a growing proprietary pipeline of DARPin® therapies in oncology. Our current research focus is in immuno-oncology.
DARPin® is a registered trademark owned by Molecular Partners AG.