Inovio Pharmaceuticals, based in Plymouth Meeting, Pa., has been awarded a $45 million grant from the Defense Advanced Research Projects Agency (DARPA) to lead a collaborative team to develop multiple treatment and prevention approaches against Ebola.

Inovio is the prime contractor on the DARPA program. Other collaborators are MedImmune, the global biologics R&D arm of AstraZeneca; GeneOne Life Science and its manufacturing subsidiary, VGXI; and professor David B. Weiner, Ph.D., professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania, Emory University and Vanderbilt University.

The Inovio-led consortium is taking a multi-faceted approach to develop products to prevent and treat Ebola infection. These programs include development and early clinical testing of:

• A therapeutic DNA-based monoclonal antibody product dMAb against the Ebola virus infection. This promising new technology has properties that best fit a response to the outbreak in that they could be designed and manufactured expediently on a large scale using common fermentation technology, are thermal-stable and may provide more rapid therapeutic benefit.
• A highly potent conventional protein-based therapeutic monoclonal antibody (mAb) product against Ebola virus infection.
• Inovio's DNA-based vaccine against Ebola, with the first patient expected to be dosed in 2Q 2015.

Pathogen specific mAbs have emerged as a viable approach for immunoprophylaxis against Ebola and other pathogens where anti-viral drugs or vaccinations are not currently available. mAbs can be administered either just before or just after exposure to the pathogen and serve to combat the immediate effects of the pathogen. Unlike vaccines, immunoprophylaxis by mAbs does not develop long term immune memory. Therefore an ideal approach would include the administration of a mAb for immediate protection and a vaccine to train the immune system for longer term protection.

Previous Ebola research studies have shown that monoclonal antibodies (such as ZMapp) could be useful in treating patients who have been infected with Ebola virus by selectively binding and neutralizing the virus in the body. Inovio already is developing dMAb products against influenza and antibiotic resistant bacteria as a subcontractor under a separate DARPA funded grant.

The proposed effort will cover preclinical development costs for the dMAb products and protein mAb candidates as well as GMP manufacturing costs and the phase I clinical study costs with the three product candidates. MedImmune will manufacture the protein mAbs and the Inovio-GeneOne/VGXI team will manufacture the DNA based products. The academic partners are leading Ebola research and medical centers at the front edge of the discovery efforts for highly potent anti-Ebola mAbs.

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. The options are contingent upon the successful completion of certain preclinical development milestones.

Due to the global concerns and immediacy of need, the consortium has employed an aggressive development timeline for the Ebola products by developing these three options in parallel, resulting in an acceleration of the initial clinical evaluation. None of these products will contain any Ebola virus or viral particles.

DARPA, an agency of the U.S. Department of Defense that creates and supports novel technologies important for national security, has selected Inovio to develop products that if successful can add to the arsenal of rapid response capabilities. Inovio's Ebola program is initially targeted to treat first responders and Ebola-infected health care workers and patients, but could potentially be widely utilized to stem the spread of the current or subsequent outbreaks.

The Ebola virus causes periodic outbreaks of a highly contagious and lethal human infectious disease marked by severe hemorrhagic fever, with a mortality rate that ranges between 50% and 90%. The infection typically affects multiple organs in the body and often is accompanied by severe bleeding. The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission. At present, there are no FDA-approved pre- or post-exposure interventions available in the event of an outbreak, laboratory accident, or deliberate misuse.

The Ebola virus is classified as a Category A Priority Pathogen by the Centers for Disease Control and Prevention. This designation prescribes an accelerated development pathway for FDA approval that determines efficacy based on two different validated animal studies followed by clinical evaluation in phase I and phase II trials to establish safety and immunogenicity for use in humans.