A new class of polyclonal antibody drugs, termed recombinant hyperimmunes, which comprise thousands to tens of thousands of antibodies, could be much more powerful than convalescent serum therapies that have been touted as a unique and viable way to address the ongoing COVID-19 pandemic.

In a study published by GigaGen Inc. (South San Francisco, CA, USA), the company has presented a novel technology for producing a new class of drug, which it calls "recombinant hyperimmunes." Convalescent serum therapies have been touted as a unique and viable way to address the ongoing COVID-19 pandemic. These therapies are powerful in that they comprise tens of thousands of antibodies and therefore have polyvalent activity against multiple drug targets and epitopes, which may improve clinical efficacy, while leveraging in vivo affinity maturation of antibodies in donors' immune systems. This is a common approach. For example, other plasma-derived drugs, such as intravenous immunoglobulin (IVIG) and anti-thymocyte globulin (ATG), are used to treat hundreds of thousands of patients globally.

However, drugs derived from blood fractions are difficult to manufacture consistently and at large scale. For example, in developing its novel COVID-19 therapy, GIGA-2050, GigaGen's screen of 50 convalescent COVID-19 donors showed thousand-fold differences in anti-SARS CoV-2 titers, with many donors producing very weak responses, which greatly complicates the ability of convalescent serum manufacturers to acquire enough high-potency product to address the COVID-19 pandemic. The phenomenon of inconsistent antibody responses to COVID-19 highlights the need to develop alternative therapeutic approaches in parallel.

GigaGen's new data highlights a new class of polyclonal antibody drugs, termed recombinant hyperimmunes, which comprise thousands to tens of thousands of antibodies. These are derived from donor B cells, and are produced recombinantly at large scale in mammalian cells. For applications such as GIGA-2050 to treat COVID-19, the result is similar to "recombinant convalescent serum," which combines the advantages of recombinant antibodies such as purity, consistency and potency, with the advantages of plasma-derived antibodies such as proven efficacy, diversity, polyvalence and in vivo affinity maturation. Using this technology, GigaGen can produce millions of doses of drug without the need to recruit more convalescent donors.

In studies, GIGA-2050 has been shown to be 100-fold more potent than convalescent serum and comprises 12,500 antibodies selected from 16 exceptional responders to COVID-19. GIGA-2050 also showed greater IgG purity than reference plasma-derived drugs and was 100 times more protective versus high-titer COVID-19 convalescent plasma using SARS CoV-2 live virus neutralization assays. GIGA-2050 has the potential to be broadly efficacious, since it binds to a variety of natural SARS CoV-2 variants in addition to its predecessor, SARS CoV.

“Our approach only requires a few donors to generate enough product to treat millions of people. No other company on Earth has the technology to produce this kind of drug. We still don't know whether vaccines and monoclonal antibodies will fail to prevent serious COVID-19, so our technology fills a critical niche to address the risk of a further escalating pandemic,” said David Johnson, Ph.D., co-founder and chief executive officer of GigaGen.

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