Advancing the Next Generation of Antibody Drugs

The World’s First Recombinant Polyclonal Drugs

GigaGen is advancing the first recombinant polyclonal antibody therapies for immunodeficiencies, infectious diseases and transplant rejection, disorders that are currently treated with polyclonal antibody therapies derived from human or animal plasma. Polyclonal antibody therapies contain a diverse array of antibodies. As such, they are ideal for diseases that comprise many targets, such as viruses that are best neutralized by antibodies binding to multiple epitopes.

Our technology copies and recreates the best immune responses from human donors who are either vaccinated or convalescent for a particular disease. This approach ensures that the diversity of antibodies in our drug candidates closely mimics that of a natural immune response. Recombinant polyclonal hyperimmunes are made in the laboratory versus being extracted from plasma. As such, they can be enriched or modified to create therapeutics that are more potent than what the natural immune response can provide.

• Anti-Hepatitis B Virus Recombinant Hyperimmune (GIGA-2339):

Hepatitis B virus (HBV) is an infection that affects more than 1 million people in the U.S. and over 350 million people worldwide. It can cause liver damage, cirrhosis and hepatocellular carcinoma (cancer of the liver). In many cases, initial HBV infection (called acute infection) resolves itself without treatment. However, in some cases the disease progresses to chronic infection. Although there is currently no cure for chronic infection, anti-HBV drugs can halt viral replication or delay progression to liver damage and cancer. Yet, these must be taken daily for life and have side effects. Even with viral suppressive treatment, the disease progresses into hepatocellular carcinoma in 20% of cases.

GigaGen is developing a recombinant polyclonal therapeutic (GIGA-2339) to treat and potentially cure chronic HBV infection. GIGA-2339 is made in the laboratory and is over 2,000 times more potent than current plasma-derived anti-HBV hyperimmune drugs. It is composed of over 1,000 antibodies against HBV surface antigens, providing better viral antigen coverage that may potentially lead to improved clearance of the virus by the body’s natural immune cells.

• IVIG + High Titer Recombinant Anti-Pathogen Hyperimmune:

Immunodeficiencies are characterized by the body’s inability to properly make antibodies, which are required to fight infections. People without a fully functioning immune system are susceptible to recurrent and severe infections caused by viruses and bacteria that healthy people would normally – and naturally – fight off. Patients with immunodeficiencies are treated with intravenous immunoglobulin (IVIG), an antibody product derived from the plasma of thousands of human donors.

GigaGen’s recombinant IVIG mirrors the antibody diversity found in healthy vaccinated or convalescent donors against specific common diseases, though it has been engineered to have significantly higher potency than plasma-derived products.

• Recombinant Human ATG:

Anti-thymocyte globulin (ATG) is used with other medications to treat transplant rejection and other inflammatory diseases. ATG is a polyclonal antibody typically obtained from plasma of rabbits or horses immunized with human lymphocytes. Since this drug is derived from animals, it can induce anti-drug antibody responses limiting its effectiveness, and it has the potential to cause allergic reactions.

GigaGen is developing a recombinant human ATG that is less immunogenic than animal-derived ATG and more consistent from batch to batch. It has the potential to provide improved efficacy with a less frequent dosing regimen for some indications.

• Anti-Rabies Recombinant Hyperimmune:

Rabies is a deadly virus transmitted to people from the bite of an infected animal. Disease can be prevented by immediate post exposure prophylaxis (PEP), which consists of rabies vaccination and treatment with plasma-derived human rabies immunoglobulin (HRIg).

Rabies is a worldwide health problem. Every year, more than 29 million people receive rabies PEP. Unfortunately, there are still tens of thousands of deaths annually from those who don’t receive the treatment. For this reason, rabies is considered a Neglected Tropical Disease and an active area of focus for the World Health Organization.

Currently, HRIg is manufactured from human plasma. GigaGen is developing a high-potency recombinant anti-rabies hyperimmune, which consists of thousands of antibodies against rabies.

• An Example of Rapid Response to Emerging Pathogens – Anti-Botulinum Toxin Recombinant Polyclonal Hyperimmune:

Botulinum neurotoxins (BoNT) are among the world’s most toxic biological substances. Produced by the bacterium Clostridium botulinum, they can cause progressive muscle paralysis and can be fatal if left untreated. While BoNTs have not been successfully used as biological weapons to date, their intentional release could significantly impact public health due to their short incubation period and high mortality rate when untreated.

Historically, treatments have relied on human or equine plasma-based polyclonal antibody drugs, which have a long and complicated production cycle with limited availability. GigaGen was recently awarded a contract from the U.S. Biomedical Advanced Research and Development Authority (BARDA), valued at up to $135.2 million, to develop a high-potency recombinant polyclonal antibody drug designed to neutralize all seven BoNT variants and a second biothreat of interest to the agency. This work builds upon a previous contract awarded by the Department of Defense for BoNT, and it is as an example of GigaGen’s platform applicability for the rapid development of recombinant polyclonal antibody drugs against high-priority emerging pathogens and toxins.