Inovio Pharmaceuticals, Inc. in collaboration with The Wistar Institute and the University of Pennsylvania announced that the first subject was dosed as part of the first-ever human study of Inovio’s DNA-encoded monoclonal antibody (dMAb™) technology. Funded fully by the Bill & Melinda Gates Foundation, this trial’s focus is on evaluating the dMAb’s (INO-A002) ability to prevent or treat Zika virus infection. The clinical results will also help to broadly advance Inovio’s dMAb programs in infectious diseases and cancer. When delivered directly into the body, the genetic codes provided by the synthetic dMAbs, instruct the body’s cells to become the factory which manufactures the therapeutic antibody products, enabling a major leap forward in antibody technology.
Dr. J. Joseph Kim, Inovio’s President and CEO, said,
This first-in-human study could provide important information about how DNA-encoded products may be used to make systemically-available complex therapeutic proteins in a consistent, dose-dependent fashion. This platform advancement, most importantly, could lead to production of other dMAb products targeting infectious diseases, cancer immunotherapy, inflammation, as well as therapies for cardiovascular disease – all with blockbuster market potential which we plan to develop with corporate partnerships, external funding and collaborations.
Inovio recently reported successful development of optimized dMAbs targeting the immune checkpoint molecule PD-1. This breakthrough preclinical data demonstrated that a single injection of synthetic designer dMAb versions of pembrolizumab or nivolumab sequences targeting PD-1 protein can be robustly redeveloped to be expressed directly in vivo in mice for up to several months. Furthermore, Inovio’s proprietary sequence optimization of the molecular design of these therapeutics resulted in significantly improved expression compared to the original PD-1 inhibitor native sequences while maintaining identical binding capabilities.
For the Zika dMAb trial, Inovio is partnered with The Wistar Institute with grant funding from the Bill & Melinda Gates Foundation to support and advance this innovative program through clinical testing. This open-label trial is a single center, dose escalation trial that will enroll up to 24 healthy volunteers who will receive up to four doses of INO-A002. The trial is led by Pablo Tebas, M.D., Professor of Medicine at the Hospital of the University of Pennsylvania.
Traditional monoclonal antibodies represent the largest segment of pharmaceutical markets today, accounting for more than $100 billion in pharmaceutical sales each year, with treatments spanning cancer, infectious diseases, inflammation and cardiovascular diseases. With its synthetic design and in-patient production, dMAb products represent a disruptive entrant to this important class of pharmaceuticals. Inovio and its collaborators have already received over $60 million in non-dilutive grant funding to advance its dMAb platform in the last few years. There is a significant interest in dMAb’s as an alternative entrant to a highly valuable overall monoclonal antibody market as well as its unique applicability for rapid responses against emerging global infectious disease threats and for addressing critical vaccine limitations.
In just the past few years, Inovio and collaborators have published multiple impactful papers consistently demonstrating potent preclinical data from the dMAb platform, with therapeutic displays spanning protection against deadly infections to eliminating cancers and lowering life-threatening levels of cholesterol. In this regard dMAbs offer unique features for rapid production, deployment and advancement of new MAb-like biologics, with much increased efficiency. In addition, the dMAb’s produced in vivo likely may have additional advantages such as expression profiles, as well as glycosylation, and unlike traditional MAb approaches, there is no reliance on in vivo tissue culture and costly or time-consuming production systems. Studies such as INO-002 are important to provide the initial data for expanding this valuable platform. In addition, Inovio collaborative studies have recently reported on the development of several dMAb checkpoint inhibitors which in animal studies reproduce faithfully the anti-cancer effects of the biologic molecules. Inovio directly and through their sponsored research has established a significant patent estate in this area.