Cornering an Ever-Evolving Coronavirus: TATX-03, a fully human synergistic multi-antibody cocktail targeting the SARS-CoV-2 Spike Protein with in vivo efficacy

ABSTRACT The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an ongoing global human health crisis and will likely become endemic, requiring novel sustainable therapeutic strategies. We report on the discovery of a fully human multi-antibody cocktail (TATX-03) targeting diversified non-overlapping epitopes on the SARS-CoV-2 spike protein that suppressed replication-competent viral titers to undetectable levels in the lungs of SARS-CoV-2 challenged hamsters upon both prophylactic and therapeutic administration. While monotherapy with two of the individual cocktail components also showed clear in vivo protection, neither recapitulated the efficacy of TATX-03. This synergistic effect was further supported by examining in vivo efficacy of these individual antibodies and corresponding combination therapy at a lower dose. Furthermore, in vitro screenings using VSV-particles pseudo-typed with spike proteins representing the SARS-CoV-2 variants of concern Alpha, Beta, and Delta showed that TATX-03 maintained its neutralization potency. These results merit further development of TATX-03 as a potential therapy for SARS-CoV-2 infection with resistance to mutagenic escape.