COV2-2130 / Vanderbilt University, IDBiologics, Twist Biosci - LARVOL DELTA

Computationally restoring the potency of a clinical antibody against Omicron. (PubMed, Nature) - "When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab4-6. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination4 and is challenging to replace with existing approaches...Our results suggest that computational approaches can optimize an antibody to target multiple escape variants, while simultaneously enriching potency. Our computational approach does not require experimental iterations or pre-existing binding data, thus enabling rapid response strategies to address escape variants or lessen escape vulnerabilities."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A combination of two human neutralizing antibodies prevents SARS-CoV-2 infection in cynomolgus macaques. (PubMed, Med (N Y)) - "The Fc-region of two neutralizing mAbs (COV2-2130 and COV2-2381) targeting non-overlapping epitopes on the receptor-binding domain of SARS-CoV-2 spike protein was engineered to extend their persistence in humans and reduce interactions with Fc gamma receptors. These results support clinical development of ADM03820 for COVID-19 prevention. This research was supported by a contract from the JPEO-CBRND (W911QY-20-9-003), 20-05, the Joint Sciences and Technology Office and the Joint Program Executive Office (MCDC-16-01-002 JSTO, JPEO), DARPA grant (HR0011-18-2-0001), NIH grant (R01 AI157155), and the 2019 Future Insight Prize from Merck KGaA."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. (PubMed, Nat Med) - "In this study, we tested a panel of anti-receptor-binding domain monoclonal antibodies (mAbs) corresponding to those in clinical use by Vir Biotechnology (S309, the parent mAb of VIR-7831 (sotrovimab)), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Eli Lilly (LY-CoV555 and LY-CoV016) and Celltrion (CT-P59) for their ability to neutralize an infectious B.1.1.529 Omicron isolate. Several mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987 and CT-P59) completely lost neutralizing activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (COV2-2196 and COV2-2130 combination, ~12-fold decrease) or minimally affected (S309). Our results suggest that several, but not all, of the antibodies in clinical use might lose efficacy against the B.1.1.529 Omicron variant."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases