Thursday, February 4, 2021 @ 3:30 am
Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein drugs known as DARPin therapeutics, and its collaborator Novartis, today announced results from a study conducted at Spiez Laboratory. The study assessed leading SARS-CoV-2 anti-infective molecules, including the collaboration's candidates ensovibep and MP0423, against new viral variants of SARS-CoV-2, including the variants first identified in the United Kingdom (UK) and South Africa (SA). These variants are associated with faster transmissibility and an ability to evade the immunity induced by some currently available vaccines and monoclonal antibodies. The study design and results were published on the research preprint service bioRxiv.
The study showed that ensovibep maintained very high potency and activity on all tested viral variants and mutants. MP0423 maintained activity against all tested viral variants and mutants, but demonstrated a slight loss of potency against the UK variant, while remaining in the therapeutic range. These data indicate that ensovibep and MP0423 are potentially a better approach than monoclonal antibody approaches, many of which have previously reported significant potency loss.
"At Molecular Partners, we built our antiviral candidates to deal with the issue of viral escape, through targeting multiple sites on the virus at once with a single molecule. As designed, this approach is providing broad efficacy against SARS-CoV-2, even in the presence of emerging mutations, unlike approaches that only target single viral sites," said Patrick Amstutz, Ph.D., CEO of Molecular Partners. "These new data are highly encouraging as we look to initiate our global COVID-19 phase 2/3 registrational study in early Q2 2021 to establish our candidates' emerging profile as potent antiviral agents with the possibility for early therapeutic intervention. Additional trials are under discussion to broaden the application space further, in other therapeutic settings. We and Novartis are committed to quickly bring our candidates to patients in need across the globe."
In the study, based on a pseudovirion model, two new SARS-CoV-2 variants first identified in the United Kingdom (UK) (lineage B.1.1.7., del69-70, del145, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H) and South Africa (SA) (early evolved variant of lineage B.1.351.; D80A, D215G, E484K, N501Y, A701V), were analyzed for infectivity in the presence of different inhibitors. The Company's two distinct multi-specific DARPin candidates, ensovibep and MP0423, were shown to protect well against these variants, as well as against multiple individual point mutations previously described. Further analyses in context of the full Brazilian P.1 lineage are ongoing. Of note, key spike mutations from the newly emerged variants identified in UK and SA, as well as from the variant detected in Brazil (lineage P.1), E484K, 69/70-deletion and N501Y, were tested individually and in the context of the full variants as described above, and were inhibited by the two DARPin candidates. These results are highly encouraging as the Company continues the clinical development of these candidates. Full data can be found in the bioRxiv publication linked above.
Ensovibep is presently in its ongoing phase 1 study which is expected to provide data in the first quarter of 2021.
About Molecular Partners' anti-COVID-19 program
Molecular Partners two antiviral DARPin candidates, MP0420 and MP0423, are designed to target multiple different sites on the SARS-CoV-2 virus simultaneously for enhanced antiviral effects and potential use as both prophylactics and treatments. The benefits of this multi-specificity include cooperative binding, extremely high potencies and potential prevention of viral ‘escape' via mutations. The candidates are formatted with a half-life extending DARPin domain that binds to human serum albumin (HSA) to support long-acting activity. All DARPin candidates are constructed to benefit from high-yield and low-cost microbial manufacturing. Molecular Partners is investigating whether the high thermal stability of DARPin molecules can be used to overcome cold-chain requirements.
Following strong preclinical data supporting the anti-COVID-19 program candidates, in October 2020 the Company entered into a collaboration with Novartis AG in the form of an option and license agreement to develop, manufacture and commercialize Molecular Partners' anti-COVID-19 DARPin program. Per the terms of the agreement, Molecular Partners will conduct Phase 1 clinical trials for MP0420 (ensovibep) and perform all remaining preclinical work for MP0423; Novartis will conduct Phase 2 and Phase 3 clinical trials, with Molecular Partners as sponsor of these trials. Upon option exercise, Novartis would be responsible for all further development and commercialization activities. Molecular Partners is also collaborating with AGC Biologics, Baccinex, and Ivers-Lee Clinical Supply Management (IL-CSM) to support development of its anti-COVID-19 program, and has reached an agreement with the Swiss Government regarding rights to purchase up to 3.2 million doses of MP0420, if it is approved in Switzerland.