Inovio Pharmaceuticals: seeking to not only improve on today’s vaccines, but change the vaccine paradigm

Inovio Pharmaceuticals is a small biotechnology company focused on vaccine development. It is at the forefront in the field of novel DNA based vaccines, a revolutionary change over conventional treatments that rely on the inoculation of actual viral particles or live attenuated viruses. The company’s platform technologies are two-fold: first is creation of the vaccine; then a unique delivery technology.

I spoke with Inovio co-founder and Chief Executive Officer Dr. Joseph Kim by phone recently to discuss his company’s vaccine technology and growing product pipeline. 

As Dr. Kim tells me, Inovio is one of the leaders in developing vaccine products for complex diseases. It has established a vertically integrated vaccine development platform approach to DNA vaccines, making them work better and at the same time improving on their delivery. 

The company now has three products in Phase II clinical trials. These are cervical dysplasia/cervical cancer, leukemia, and hepatitis C (HCV). The DNA vaccines have demonstrated “best in class” T-cell responses in both cervical dysplasia and HIV in early stage studies. 

DNA vaccines may be superior to conventional ones in several important ways. According to Dr. Kim, vaccines based on DNA plasmids are able to maximize the immune system’s ability to react, generating a strong antibody and T-cell response upon treatment. Antibody generation makes for good disease prevention while T-cell production enables disease treatment. Other than live viruses, few other vaccines have been able to achieve such a robust response.

Another advantage of DNA vaccines is their ease of production, Dr. Kim informs. Conventional vaccines involve a long process often requiring materials to be frozen along the entire distribution/storage chain. This is not an issue with DNA vaccines, which have attributes that allow for fast product generation, ease of manufacture and delivery. 

But just as important as vaccine development is proper drug delivery, which brings us to Inovio’s other technology platform. It has always been a challenge to get DNA into cells; its negative charge causes it to be naturally repelled by the lipid membrane. The technology developed by Inovio is based on electroporation. In a technique proprietary to the company, a needle injects DNA plasmids into the skin or muscle tissue, quickly followed by the application of an electric field that opens the cell membranes, allowing the plasmids to enter the cells. 

Once inside, the DNA instructs each cell to produce one or more antigens for the cancer or infectious disease for which it was coded. These antigens then elicit a targeted and robust immune response. Antigens produced in this manner are akin to material that would otherwise be injected during a conventional vaccination. As they are pumped out by cells transfected by the DNA vaccine, these antigens bring in T-cells, macrophages, antigen-presenting cells- all parts of the immune response system. The treatments have been safe and well tolerated in early studies.

Getting into a bit more detail, Dr. Kim described the way each vaccine is designed. The company produces what it calls a SynCon, or Synthetic Consensus, DNA sequence for each vaccine. The sequences are designed completely in-silico – a first for any company. Based on Inovio’s understanding of viral genes, a single optimized sequence can be generated for activity against multiple viral strains.

Lining up dozens or even hundreds of viral sequences, a novel synthetic sequence is designed by combining the most important parts of these sequences into a single sequence. Genes selected may be due to immunological importance, dominance, or because the region is highly conserved. This newly created SynCon sequence is unique to any naturally occurring sequence and is fully patentable, with a 20-year patent life. DNA plasmids created from this sequence give broader and stronger immune responses, says Dr. Kim. 

Research remains the focus of the company even as its pipeline continues to grow. According to Dr. Kim, Inovio’s strategy is to take compounds through Phase I or Phase II proof-of-concept development, then outlicense to a partner for later stage clinical trials, ploughing the money back into research. 

The company has been highly successful in obtaining non-dilutive third-party funding, particularly research & development grants and clinical trial support from outside agencies. Inovio continues to be active in searching for new partners.

On the clinical trial front, Dr. Kim reviewed some key ongoing studies, many with upcoming data read-outs. VGX-3100 is currently in a Phase II randomized, double-blinded, placebo controlled trial for women with cervical dysplasia. 148 patients categorized with stage CIN 2/3 have been recruited for the trial. In earlier studies, women treated with three doses of VGX-3100 exhibited strong and lasting levels of T-cell response, exceeding that seen for any other competitor vaccines.

VGX-3100 differs markedly from cervical cancer vaccine Merck’s Gardasil and GSK’s Cervarix, both of which are preventative vaccines targeting the human papillomavirus (HPV), the cause of 99% of cervical cancers. Inovio’s vaccine on the other hand is a therapeutic, treating the disease after an HPV infection has caused a cervical dysplasia (pre-cancerous) or cancer. It targets the HPV oncogenes E6 and E7 for Types 16 and 18 HPV, which are the cause of 70% of cervical cancers. Results from the Phase II trial are expected in the second half of 2013. If successful, this wholly owned product will be partnered for further development.

In leukemia, Inovio has a Phase II trial in collaboration with the University of Southampton with interim data expected in 2012. The DNA vaccine is being tested in patients with chronic myeloid leukemia and acute myeloid leukemia. It targets well-known Wilms’ tumor gene 1 (WT1). WT1 is highly expressed in leukemias and is thought to be an oncogene (i.e. cancer-causing). 

The third Phase II product is HCV vaccine ChronVac-C in development by partner ChronTech Pharma. ChronTech is enrolling patients in a Phase IIb study testing two vaccinations of ChronVac-C in combination with interferon and ribavirin compared to interferon plus ribavirin alone. Interim results from this study should be available in the first half of next year. 

Phase I studies of the HCV vaccine were very encouraging, although results were from only six patients. Of the six patients receiving ChronVax-C plus standard of care (SOC), five (83%) achieved a sustained viral response after just 24 weeks of treatment. This is approximately double the cure rate of SOC alone in half the time. It is also comparable to results seen for newly approved Incivek from Vertex but without the pill burden and prolonged side-effects. Interestingly, both ChronVax-C and Incivek target the same portion of the hepatitis C virus. 

Dr. Kim went on to talk about the company’s earlier stage projects; these are HIV, pandemic flu, and seasonal flu. Inovio’s HIV vaccine work is well funded by external partners, including the U.S. military, the National Institute of Allergy and Infectious Diseases, and the HIV Vaccine Trials Network. Three separate vaccines against HIV are in development, targeting multiple subtypes and geographies; they are PENNVAX-B, PENNVAX-G, and PENNVAX-GP. 

Data from clinical trials for PENNVAX-B, which targets strains prevalent in North America and Western Europe, are expected by year-end. 

A Phase I study of VGX-3400X has generated positive proof-of-principle data against the H5N1 avian flu using intramuscular injection. Inovio is now testing the treatment when administered intradermally. Dr. Kim explains that while intramuscular injections result in high T-cell production, prophylactic, or preventative therapies, require high antibody generation, which is best achieved through intradermal injections. Data from the study are expected in the fourth quarter. 

With the biggest hurdle to market but also the greatest potential is a potential universal flu vaccine. Dubbed VGX-3510, the Phase I clinical study of this product is now enrolling with the first interim data expected in the first quarter of 2012. The DNA construct for this vaccine is designed to protect against seasonal and pandemic subtypes and cover both known as well as newly emerging strains within these subtypes. 

As Dr. Kim sees it, with their products and technology, Inovio seeks to not only improve on today’s vaccines, but change the vaccine paradigm.