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Two papers out from $REGN in @ScienceMagazine describing the company's investigational antibody cocktail approach to protect against #COVID19. Paper 1 describes pairs of highly potent (pM neutralization potency) non-competing mAbs that block the viral spike protein.
The REGN10933+REGN10987 cocktail is currently being tested in clinical trials:
https://clinicaltrials.gov/ct2/show/NCT04426695 and https://clinicaltrials.gov/ct2/show/NCT04425629
https://clinicaltrials.gov/ct2/show/NCT04426695 and https://clinicaltrials.gov/ct2/show/NCT04425629
The second $REGN paper describes a phenomenon of rapid mutational escape, where #SARSCoV2 spike protein is able to evolve resistance to single mAb-based blocking approaches in vitro. However, the application of a non-competing antibody cocktail did not result in escape mutants.
Papers here:
https://science.sciencemag.org/content/early/2020/06/15/science.abd0827
https://science.sciencemag.org/content/early/2020/06/15/science.abd0831
https://science.sciencemag.org/content/early/2020/06/15/science.abd0827
https://science.sciencemag.org/content/early/2020/06/15/science.abd0831
Piece from @JAMA_current describes some of the challenges in developing mAb-based approach:
1. Because most people with early infection recover, the clinical end points needed to demonstrate a benefit relative to placebo are not easily achieved.
1. Because most people with early infection recover, the clinical end points needed to demonstrate a benefit relative to placebo are not easily achieved.
2. It may be difficult to demonstrate benefit in patients with more severe disease, in whom inflammation and coagulopathy may be more important than viral replication.
3. Immune enhancement of COVID-19. Categories of possible disease enhancement include antibody-mediated enhancement of viral entry and replication in target cells (Fc-bearing monocytes or macrophages) and virus-antibody immune complexes and the associated cytokine release.
