Symphogen is developing recombinant polyclonal antibodies (rpAb) for infectious disease targets. Recombinant pAbs hold great promise as a new way to prevent and treat bacterial and viral infections, because of their ability to capture the diversity and specificity of the natural human immune response, with the added benefit of a potentially better safety profile than current treatments.
Symphogen’s infectious disease program is currently comprised of Sym002 for the prevention or treatment of anti-vaccinia virus-related infections, Sym003 for the prevention of respiratory syncytial virus infections, Sym006 against an undisclosed bacterial target and Sym008 against an undisclosed infectious disease target. Symphogen is focusing its initial infectious disease programs on the replacement of plasma-derived immunoglobulins and monoclonal antibodies.
Immunoglobulins, the first generation of antibody therapeutics, have been in medical use for many years as prophylactic treatment in a range of infectious diseases. Immunoglobulins are isolated from blood of healthy or vaccinated donors, and in certain cases animals or donors who have recovered from a specific disease. Although immunoglobulin products are well tolerated and reflect the diversity of the natural immune system, their use is associated with several disadvantages. These limitations include: low efficacy since only a fraction of the antibodies will be specific to a particular antigen; safety issues due to the risk of disease transmission via infected blood; batch-to-batch variations; and supply shortages due to dependency on donor blood availability.
Symphogen believes that a recombinant pAb therapeutic may address the shortcomings of immunoglobulins for the prevention of infection. The Symplex™ technology is able to identify diverse repertoires of target-specific, fully human antibodies. These pAbs are more pure than immunoglobulins, and therefore eliminate the risk of infectious disease transmission. Additionally, because Symphogen’s pAbs are produced recombinantly using industrial manufacturing techniques, they are not subject to supply limitations or batch-to-batch variations like immunoglobulins.
Monoclonal antibodies (mAb) are emerging as another method for treating infectious disease. Their ability to bind to a specific part of the surface of an invading bacteria or virus provides a high degree of specificity. However, mAbs tend to lack appropriate efficacy against diseases caused by complex target antigens, such as bacterial and viral targets. Neutralization or elimination of a given pathogen depends on obtaining a sufficient high number of antibodies binding on the surface of the antigen, but due to their monospecificity, mAbs show limited binding to the antigen. Thus, a mAb may not be able to provide the antibody density needed to eradicate the pathogen. Additionally, because many pathogens are able to rapidly mutate their genetic sequence, not all strains may be recognized by a single mAb, which can lead to bacterial and viral drug resistance.
Recombinant pAbs may provide additional therapeutic benefits over mAbs. While mAbs can only bind to one specific area on the surface of an infectious agent, pAbs capture a broader representation of antibodies and therefore may provide a more diverse immune response. The several different antibodies in the polyclonal mixture bind to different structures on the surface of the antigen, thereby increasing the likelihood that the antigen will be neutralized or eliminated. PAbs are also able to maintain high specificity and affinity in the range of mAbs. A recombinant pAb mixture may also be better able to cover different mutant strains of a bacteria or virus, therefore reducing the likelihood of drug-resistant pathogens.
Sym003
Sym006
