AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans

Loo, Y.-M.; McTamney, P. M.; Arends, R. H.; Gasser, R. A.; Abram, M. E.; Aksyuk, A.; Diallo, S.; Flores, D. J.; Kelly, E. J.; Ren, K.; Roque, R.; Rosenthal, K.; Streicher, K.; Tuffy, K. M.; Bond, N. J.; Cornwell, O.; Bouquet, J.; Cheng, L. I.; Dunyak, J.; Huang, Y.; Rosenbaum, A. I.; Andersen, H.; Carnahan, R. H.; Crowe, J. E.; Kuehne, A. I.; Herbert, A. S.; Dye, J. M.; Bright, H.; Kallewaard, N. L.; Pangalos, M. N.; Esser, M. T.

Despite the success of SARS-CoV-2 vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of COVID-19. Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct non-overlapping epitopes on the spike protein receptor binding domain to potently neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and abrogate effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry. Together, these two mAbs create a higher barrier to viral escape and a wider breadth of coverage, neutralizing all known SARS-CoV-2 variants of concern. In a non-human primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, while therapeutic administration accelerated virus clearance from lung. In an ongoing Phase I study in healthy participants (NCT04507256), 300 mg intramuscular AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers >10-fold above those of convalescent sera for >=3 months, which remained 3-fold above those of convalescent sera 9 months post-AZD7442 administration. Approximately 1-2% of serum AZD7442 levels were detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentrations suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.