Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein therapeutics known as DARPin therapeutics, has identified multiple potent monospecific DARPin proteins which neutralize samples of the SARS-CoV-2 virus. The company has engineered these proteins into trispecific antiviral candidates that target three parts of the viral “spike” protein, which is essential for viral entry into human cells. Multispecific inhibition represents a differentiated approach to treating COVID-19, offering potentially greater therapeutic efficacy and reduced potential for the development of viral drug resistance.
“In this period of unprecedented global need, we believe it is imperative that we investigate the potential of our DARPin platform against COVID-19. Among the many efforts underway, a DARPin therapeutic that can neutralize multiple sites of the viral spike protein in a single drug could be an important tool in our fight against the virus,” said Patrick Amstutz, Ph.D., Chief Executive Officer of Molecular Partners. “I am truly encouraged by the spirit of collaboration across academia and industry in response to this challenging time. We have progressed to hit candidate selection in a month, and expect to further leverage the rapid, high-yield nature of DARPin protein manufacturing to chart a rapid path to human trials.”
Research performed by Molecular Partners in collaboration with virologists at the Spiez Laboratory, a division of the Swiss Federal Office for Civil Protection, has characterized hundreds of monospecific and multispecific DARPin proteins with strong binding and neutralizing qualities against multiple epitopes on the SARS-CoV-2 spike protein that are crucial for infection. Preliminary data indicate that multispecific DARPin molecules show synergistic antiviral activity, exceeding the activity of their constituent parts. A multispecific DARPin lead candidate will be chosen based on its capability to perform three distinct mechanisms of action (illustrative graphic): blocking binding of the human ACE2 receptor, the virus’s primary docking mechanism to host cells; blocking binding of a specific protease essential for spike protein activation; and “handcuffing” the spike protein, preventing the conformational change it undergoes prior to injection of viral RNA into the human cell. The final candidate is also expected to have its half-life enhanced with a DARPin domain that binds to human serum albumin (HSA) to support long-acting activity.
The construction of multispecific candidates from monospecific proteins is the foundation of Molecular Partners’ drug discovery engine, and has yielded multiple clinical candidates in other indications.
Molecular Partners is proceeding with expedited preclinical testing to select a lead candidate. The company has verified available manufacturing capacity and is targeting readiness of Good Manufacturing Practice-compliant drug product in Q3 2020.