GigaGen Announces Publication of Research Describing a New Class of Drugs, Recombinant Hyperimmunes, Including its Novel COVID-19 Therapy, GIGA-2050

GigaGen Inc. recently announced a new submission to bioRxiv, titled Capturing and Recreating Diverse Antibody Repertoires as Multivalent Recombinant Polyclonal Antibody Drugs. In this study, GigaGen presents 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.

Yet, drugs derived from blood fractions are difficult to manufacture consistently and at large scale. For example, in developing 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.

Key results include:

-Successfully demonstrated consistent production of the GIGA-2050 drug candidate, a mixture of 12,500 anti-coronavirus antibodies

-GIGA-2050 showed greater IgG purity than reference plasma-derived drugs

-GIGA-2050 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

In addition to a recombinant hyperimmune for COVID-19, the data show broad applicability through proofs-of-concept for a Zika hyperimmune without risk of antibody-dependent enhancement (ADE), a high-potency spike-in mixture for primary immune deficiency, and a recombinant version of ATG for transplant tolerance.

David Johnson, PhD, Co-founder and Chief Executive Officer of GigaGen, added “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.”

GigaGen is advancing transformative antibody drugs for infectious diseases, transplant rejection, and checkpoint resistant cancers by leveraging industry-leading, single-cell technologies. Its technology uniquely captures and recreates complete immune repertoires as functional antibody libraries. This approach has enabled the creation of the first recombinant polyclonal immunoglobulin therapies, which overcome current limitations of plasma-based products. GigaGen’s technology has also filled a pipeline of monoclonal antibodies with unique properties against known and novel oncology targets with the potential to translate into therapies with improved efficacy and safety profiles.