Inovio Pharmaceuticals has announced that the development of its DNA-based monoclonal antibody programme received a boost from two peer-reviewed scientific papers that demonstrate their impact on prostate tumors and in preventing infection from a pneumonia-causing bacteria in preclinical studies.
Dr. J. Joseph Kim, Inovio's president and CEO, said, “Many of the top-selling drugs on the market today are monoclonal antibodies; our dMAb products may improve upon this class using our synthetic design and in vivo production. In fact, we are advancing our first dMAb product – our therapeutic Ebola product funded by DARPA – into human testing next year, opening the path for commercializing these new products to treat cancer and infection. These two newly published studies further support that Inovio’s potent dMAb platform could be expanded to target cancer and bacterial diseases along with viral infectious diseases. Our dMAb program represents a new application of our potent DNA technology platform to develop valuable new treatments for cancers and infection.”
An article in the journal Cancer Immunology, Immunotherapy detailed how the dMAbTM construct against prostate specific membrane antigen (PSMA) produced monoclonal antibodies that shrank prostate tumors in a preclinical animal model. The article is entitled, “Novel cancer immunotherapy with DNA-encoded anti-prostate-speci?c membrane antigen monoclonal antibody,” by Inovio researchers and collaborators.
This research publication is significant because it is the first to report on the use of Inovio dMAb technology to develop novel monoclonal antibody-based therapies against cancer targets. This new dMAb construct utilizes engineered synthetic DNA to encode therapeutic monoclonal antibodies targeted to bind PSMA. When delivered directly into the body, the genetic instructions provided from the dMAb construct enable the patient’s own cells to become the factory which manufactures the therapeutic monoclonal antibody products. The PSMA dMAb antibody was expressed in high levels directly in mice and successfully regressed human prostate cancer cells grown in transgenic mice. Inovio has previously published several papers demonstrating its dMAb product candidate’s ability to treat multiple virus targets such as flu, dengue, chikungunya, and HIV.
The anti-cancer dMAb products work by binding the antigens on the cancer cells and killing them by an antibody dependent cytotoxicity (ADCC) mechanism in conjunction with natural killer (NK) cells. These results indicate the potential clinical utility of the dMAb therapeutic strategy against prostate cancer as well as other cancers. The data is especially interesting since the anti-cancer dMAb products utilize an NK cell-killing mechanism which is distinct from the killer T cell mechanisms generated by Inovio’s cancer vaccine products like INO-5150 and INO-5401.
In another first, Inovio also published results showing its dMAb constructs targeting antibiotic-resistant bacteria protected mice when challenged with a lethal dose of drug-resistant pseudomonas -- a pneumonia-causing bacteria. Pseudomonas infections usually occur in people in the hospital or with weakened immune systems. The CDC reports each year that more than two million Americans acquire antibiotic-resistant infections that are becoming increasingly more difficult and costly to treat. The bacteria can cause infections of the blood, pneumonia, and infections following surgery that can lead to severe illness and death.
To design an effective treatment, Inovio engineered dMAb constructs encoding two pseudomonas antigens. The constructs were protective against lethal pneumonia, prevented severe lung pathology and even exhibited enhanced protective activity when combined with antibiotics. This paper is also significant for Inovio to demonstrate that dMAb constructs could be successfully designed to generate bispecific monoclonal antibodies. Bispecific monoclonal antibodies are engineered synthetic antibodies which could simultaneously bind two different antigens, and this technique is very difficult to achieve using traditional protein-based monoclonal technology. These results further support the sophisticated capabilities built into Inovio dMAbTM technology. Results from this study were published in Nature Communications, in an article entitled, “DNA-delivery of mono- and engineered bispecific monoclonal antibodies protect against multidrug resistant Pseudomonas aeruginosa,” authored by Inovio and its collaborators at The Wistar Institute and MedImmune, AstraZeneca’s global biologics research and development arm.
Funded with over $60 million in R&D support from top agencies like DARPA, NIH, and the Gates Foundation, Inovio dMAb products could extend the medical benefits that marketed monoclonal antibodies have already achieved, and even potentially address diseases that conventional monoclonal antibodies cannot. For instance in immuno-oncology, Inovio is already developing PD-1/PD-L1 as well as other checkpoint inhibitors in its cancer dMAb portfolio.
Even though conventional monoclonal antibodies represent one of the most successful segments of the biotechnology market, accounting for over $50 billion in sales today, they are still costly and time consuming to develop, produce and study. They are manufactured outside the body in bioreactors, typically requiring costly large-scale manufacturing facility development and laborious production. Inovio’s disruptive dMAb technology has the potential to overcome these limitations by virtue of their simplified design, rapidity of development, product stability, ease of manufacturing and deplorability, and cost effectiveness, thereby providing potential new avenues for treating a range of diseases.