Inovio Pharmaceuticals, MedImmune and the University of Pennsylvania join forces to tackle influenza and antibiotic-resistant bacteria

Inovio Pharmaceuticals is to collaborate with scientists from the Perelman School of Medicine at the University of Pennsylvania and MedImmune, the global biologics research and development arm of AstraZeneca, to develop DNA-based monoclonal antibodies for the treatment of infectious diseases.

The study has been awarded US$12.2m by the Defense Advanced Research Projects Agency (DARPA).

Together, the three organisations will develop and assess the DNA mAbs in preclinical studies using technology developed by the University of Pennsylvania (Penn) and licensed by Inovio. The collaboration will focus on three disease areas – influenza virus, Pseudomonas aeruginosa and Staphylococcus aureus.

Joseph Kim, Inovio's President and CEO, said: ‘Monoclonal antibody technology has already achieved multiple market-proven product successes, and we believe DNA-based mAb technology could significantly extend the medical benefits and efficiency of this concept. In previous preclinical studies our DNA-based mAbs demonstrated robust virus neutralisation and protected treated animals challenged with a lethal virus.’

Monoclonal antibody technology has already achieved multiple market-proven product successes, and we believe DNA-based mAb technology could significantly extend the medical benefits and efficiency of this concept

MedImmune developed the first mAb approved by the US Food & Drug Administration for the prevention of an infectious disease, and Inovio pioneered the development of DNA-based vaccines and immunotherapies using a delivery mechanism known as electroporation.

The project proposes an entirely new technology, initially developed at Penn in the lab of David Weiner, Professor of Pathology and Laboratory Medicine, to provide a platform to protect people against emerging infections through the development of novel synthetic antibodies produced by the patients themselves.

Over the last few decades, monoclonal antibodies (mAbs) have become one of the most important approaches to treat a variety of diseases but they are expensive and time-consuming to produce and study. They are manufactured outside the body, typically requiring costly large-scale laboratory development and production, and also require frequent administrations and have a limited duration of potency in the body.

Inovio says DNA-based mAbs have the potential to overcome these limitations by virtue of their simplified design, product stability, manufacturing, dosing frequency, and cost effectiveness, thereby providing potential new avenues for the treatment of disease.

The shift seen in new mAb technologies is that the DNA for a monoclonal antibody is encoded in a DNA plasmid, which is produced using cost effective and scalable fermentation techniques. These plasmids are delivered directly into cells of the body using electroporation and the encoded mAbs are then produced by these cells. Using this approach, previously published studies show that a single administration of a highly optimised DNA-based monoclonal antibody targeting HIV virus in mice generated antibody molecules in the bloodstream.

This collaboration aims to demonstrate that the DNA plasmids containing optimised DNA sequences encoded to generate disease-specific mAbs can activate sufficient quantities of specific antibodies in the body to be protective against pathogens. Using the capabilities and advantages of synthetic DNA plasmids delivered using electroporation, the team will construct and evaluate multiple DNA mAbs.

Successful completion of the initial preclinical activities under the DARPA grant aims to lead to clinical studies on selected product candidates to be funded under a future increment to the award.