DARPins offer a differentiated approach to treating COVID-19 through a single molecule that can engage up to three parts of the SARS-CoV-2 virus simultaneously to neutralize the virus through multiple mechanisms. This offers potentially broader efficacy – across both therapeutic and prophylactic settings – and reduced potential for the development of viral drug resistance. DARPins are also produced through rapid, high-yield microbial fermentation for potential speed and cost advantages over mammalian cell production employed for antibodies.
In 2020, Molecular Partners entered into a collaboration with Novartis to develop, manufacture and commercialize MP0420 and MP0423.
COVID-19 represents the biggest disease burden in the world today through its impact on healthcare, society and economies. Vaccines will be important in the fight against COVID-19 but are unproven for coronaviruses and are expected to be variably effective, particularly in high risk groups. Almost all ongoing novel biologic therapeutic efforts aim to use receptor binding domain (RBD)-targeting antibodies for the treatment or prevention of the disease, which may lead to a global selection pressure for strains with mutations in this domain.
DARPin molecules can be used to rapidly generate diverse, multifunctional drug candidates, capable of binding to multiple targets at once. The development of tri-specific candidates with cooperative binding could allow for greater potencies and prevention of viral escape via mutations. Our anti-COVID-19 DARPin candidates are also built with a half-life enhancing DARPin domain that binds to human serum albumin (HSA) to support long-lasting activity. HSA is found in elevated levels in the lung which may provide a further benefit in a respiratory viral setting.
MP0420 and MP0423 are unique tri-specific DARPin candidates that have shown cooperative target binding and exhibit among the strongest virus inhibition potency reported to date. MP0420 targets three different epitopes of the RBD simultaneously, and MP0423 targets three different parts of the coronavirus spike protein simultaneously. These include: the RBD, S1 N-terminal domain (NTD) and S2 domain. MP0423 shows the ability to inhibit the virus beyond RBD neutralization by tackling multiple mechanisms of action in parallel.