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IONTAS Identifies Novel SARS-CoV-2 Neutralizing Antibodies

Potent antibodies shown to retain binding to major COVID-19-causing “South African” variant

IONTAS
Image shows the spike protein of SARS-CoV-2 which is used to gain entry into cells by binding to ACE2 on lung cells. The “Receptor Binding Domain” (RBD) is shown in orange and the part of the RBD which contacts ACE2 is shown in yellow.

Many of the neutralizing antibodies under development bind this “yellow” site but this is also where mutations occur in variants such as the “South African” and “Kent” variants causing some antibodies to fail.
IONTAS

CAMBRIDGE, UK, PORTO, PORTUGAL, and LONDON, UK — March 22, 2021 — IONTAS Limited (IONTAS) and FairJourney Biologics S.A (FJB)., leaders in the discovery and optimization of fully human antibodies, have announced the identification of neutralizing antibodies, which bind to multiple emerging SARS-CoV-2 variants. The results, generated from a combination of phage display technology and B-cell receptor repertoire sequencing of hospitalized COVID-19 patients, have identified potent neutralizing antibodies with distinct mechanisms of action. Based on this approach, the company has developed a panel of therapeutic candidates.  

SARS-CoV-2 virus enters the body as a result of the viral spike protein binding to the ACE2 protein on the surface of lung cells. This interaction is driven by a small region of the spike protein and the majority of antibodies currently undergoing clinical trial bind to this site. However, this site has changed in some of the emerging viral variants, reducing or abolishing the effect of some clinical candidates. Drug candidate antibodies developed by IONTAS to this same site have been shown to retain binding to the emerging variants.  

An alternative approach for tackling variants is to target alternative regions of the virus which have a greater degree of conservation, making escape variants less likely. GSK/VIR Biotechnology recently announced a successful Phase 3 trial of such an antibody. VIR-7831 is an antibody which binds to a region of the spike protein which is highly conserved between SARS-CoV-2 and SARS-CoV-1 (A distantly related virus responsible for the outbreak of Severe Acute Respiratory Syndrome in 2003). VIR-7831 has shown an 85 percent reduction in hospitalization and death during the COMET-ICE clinical trial. The partnership is now seeking Emergency use Authorization in the US and other regions.  

A sub-set of the IONTAS antibodies, show a similar functionality to VIR-7831, by binding to sites conserved both in the recently emerging SARS-CoV-2 variants as well as to the more distantly related SARS-CoV-1 virus. 

“The first wave of antibody drugs for treating COVID-19 was focused on achieving maximal neutralization to the original SARS-CoV-2 strain first identified in Wuhan," commented Dr. John McCafferty, CSO at IONTAS. "This led many companies to a target site on the virus which is very effective for neutralization but also prone to genetic change. Second generation drug candidates need to anticipate the emergence of new variants by targeting more conserved sites. IONTAS has identified drug candidates which neutralize by targeting conserved regions of the virus. We now seek partners to help develop these to better position the world in tackling this dreadful disease.”