Inovio's DNA monoclonal antibodies cause mAbs to be manufactured in the body

Monoclonal antibodies (mAb) have become one of the most valuable therapeutic technologies of recent years. They are designed to enhance the immune system's ability to regulate cell functions. mAbs are designed to bind to a very specific epitope (area) of an antigen or cell surface target and can bind to almost any selected target. They have the unique ability to alert the immune system to attack and kill specific cancer cells (as in the case of Yervoy®) or block certain biochemical pathways (such as those leading to rheumatoid arthritis, as in the case of Remicade®).

mAb technology, however, does have limitations. Delivered by passive administration, meaning they are manufactured outside the body, mAbs typically require costly large-scale laboratory development and production. Additional limitations include the necessity for repeat administrations and their limited duration of in vivo potency.

Inovio has overcome many of the limitations associated with mAb technology. With Inovio's technology, the DNA for a monoclonal antibody is encoded in a DNA plasmid and delivered directly into cells of the body using electroporation, causing the mAbs to be "manufactured" in the body by these cells – not outside of the body like conventional mAb technology. Using this approach, Inovio published that a single administration of a highly optimized DNA-based monoclonal antibody (dMAbTM) targeting HIV virus in mice generated antibody molecules in the bloodstream possessing desirable functional activity including high antigen-binding and HIV-neutralization capabilities against diverse strains of HIV viruses. Inovio also showed that its mAb technology targeting Chikungunya virus (CHIKV) completely protected 100% of treated mice from a lethal CHIKV injection in preclinical studies.

Inovio's transformational approach could be applied to develop active monoclonal antibody products against multiple therapeutically important diseases including cancers as well as inflammatory and infectious diseases. Combined with the significantly favorable cost structure of Inovio's DNA-based technology in comparison to conventional monoclonal antibody technology, active in-body generation of functional monoclonal antibodies in humans has the potential to significantly expand the range of targetable diseases.

The desirable characteristics associated with Inovio’s novel DNA-based monoclonal antibody technology has attracted the attention of third party organizations. Inovio has been awarded two grants from the Defense Advanced Research Projects Agency (DARPA) to lead collaborative teams to develop dMAbs for the treatment and prevention of multiple infectious disease indications.

Under the first grant, received in October 2014, DARPA awarded Inovio, MedImmune, and the University of Pennsylvania $12.2 million for a collaborative study to develop and assess dMAbs against influenza virus, Pseudomonas aeruginosa and Staphylococcus aureus in preclinical studies. This collaboration aims to demonstrate that the DNA plasmids containing optimized DNA sequences encoded to generate disease-specific mAbs can activate sufficient quantities of specific antibodies in the body to be protective against a pathogen challenge. Successful completion of the initial preclinical activities under this grant aims to lead to clinical studies on selected product candidates to be funded under a future increment to the award.

In April 2015, Inovio received a $45 million grant from DARPA to lead a collaborative team in the development of multiple treatment and prevention approaches against Ebola, one of which includes a therapeutic DNA-based monoclonal antibody (dMAb™) developed by Inovio. Two additional approaches include a highly potent conventional protein-based therapeutic mAb and Inovio's DNA-based vaccine. Included in this collaboration is MedImmune, GeneOne Life Sciences and its manufacturing subsidiary, VGXI, Inc., the University of Pennsylvania, Emory University and Vanderbilt University. The grant covers pre-clinical development costs for the dMAb and mAb candidates as well as GMP manufacturing costs and phase I clinical study costs of the three product candidates. The funding period is over two years and covers a base award of $21 million and an option award of $24 million. The development proposal includes a second option of $11 million to support additional product supply and clinical development activities, which is contingent upon the successful completion of certain pre-clinical development milestones.