Inovio Biomedical (AMEX: INO) is developing a robust pre-clinical and early clinical stage pipeline of innovative DNA-based vaccines and therapeutics that target cancer, influenza, and other infectious diseases (e.g. HIV) based on its SynCon DNA vaccine construct and electroporation DNA delivery technology platforms.
Inovio's electroporation-delivered DNA-based vaccines / therapeutics are based on the application of controlled electrical pulses at the molecular level (i.e. this is not like electro-shock therapy or touching a live electric wire!) to create temporary pores in cell membranes and enable increased cellular uptake. This delivery method is expected to yield safer results as compared to alternate gene therapy approaches that may utilize viruses to deliver genetic material to the target tissue or tumor. The Company also has access to formulation and manufacturing technology / IP through its controlling ownership in VGX Pharmaceuticals.
Inovio is developing its universal and avian influenza vaccines in collaboration with scientists from the University of Pennsylvania, the National Microbiology Laboratory of the Public Health Agency of Canada, and the NIH's Vaccine Research Center. Other partners and collaborators include Merck (NYSE: MRK), Tripep, University of Southampton, National Cancer Institute, and the HIV Vaccines Trial Network. Below is an outline of what investors can expect in the near to intermediate term for Inovio with regard to expected clinical trial catalysts and news flow from the Company and its collaborators / development partners.
In May 2004, Merck licensed the Company's electroporation-based technology for the delivery of proprietary DNA vaccine candidates. The agreement granted Merck worldwide non-exclusive rights to use Inovio's electroporation technology for the intramuscular delivery of DNA vaccines and the deal included upfront / milestone payments, development fees, royalties, and a supply agreement. Merck has two ongoing, early-stage clinical programs and Inovio has received a pair of $2 million milestone payments as part of the Investigational New Drug (IND) applications filed by Merck.
On 10/5/09, Inovio announced that a combination of its synthetic consensus (SynConTM) H1N1 influenza vaccine candidates achieved protective antibody responses against the novel pandemic influenza A/H1N1 (2009) in 100% of tested ferrets (which is a standard animal model for preclinical testing of human influenza vaccines). Inovio is focused on developing DNA-based influenza vaccines able to provide broad protection against known as well as newly emerging, unknown seasonal and pandemic influenza strains. Inovio could potentially file an Investigational New Drug (IND) application with the FDA during 1H10 for permission to begin clinical trials in humans for a H1N1 flu vaccine based on my 10/7/09 phone interview with the Company's investor relations contact, Bernie Hertel.
On 10/5/09, Inovio also announced interim safety / immunogenicity data from its therapeutic cervical cancer vaccine (VGX-3100) trial. VGX-3100 is a DNA vaccine targeting the E6 and E7 proteins of human papillomavirus (HPV) types 16 and 18 and is delivered via in vivo electroporation. The vaccine was found to be generally safe and well tolerated, and achieved significant cellular and humoral immune responses at the lowest dose administered. This Phase I clinical trial is designed to test the safety and immunogenicity of VGX-3100 in women with a previous history of cervical intraepithelial neoplasia (CIN) 2/3, a precursor lesion prior to the development of cancer.
This dose-escalation study is enrolling patients in three cohorts of six subjects each with DNA vaccine doses at 0.6 mg (0.3 mg each of two DNA plasmids), 2.0 mg, and 6.0 mg. The immunization regimen consists of each subject receiving three immunizations at the indicated dose. The vaccine is delivered using Inovio's proprietary CELLECTRA intramuscular electroporation delivery device. The VGX-3100 clinical trial is now enrolling the second cohort of six patients. Inovio expects full enrollment of all three cohorts during 1H10 and full analysis of immunogenicity / safety data by 3Q10. In addition, interim results on the second cohort of six patients are expected during 1Q10.
VGX-3400 is a proprietary, prophylactic DNA vaccine candidate being developed by Inovio to prevent infection with the avian influenza (H5N1). The vaccine is being delivered using Inovio's CELLECTRA DNA Delivery System. The plasmid vaccine is delivered into muscle tissue with the assistance of electroporation with the goal of achieving expression of the H5N1 influenza antigens. Inovio expects to initiate a Phase I clinical trial for this DNA vaccine in Europe before year end and the Company's clinical team is fulfilling information requests from the FDA relating to its previously-filed IND. Based on my 10/7/09 phone interview with the Company's investor relations contact, Bernie Hertel, Inovio could potentially receive a FDA response on the IND by year-end and begin a Phase 1 clinical trial for VGX-3400 in humans during 1Q10.
Inovio's partner, the HIV Vaccines Trial Network (HVTN), has completed enrollment of 120 subjects in its Phase I clinical study of the Company's PENNVAX-B preventative HIV vaccine (against HIV clade B, the prevalent HIV strain in North America and western Europe) without electroporation. Inovio expects to report results of this study by year end. In addition, an IND has been submitted for a second prophylactic trial, using electroporation to deliver PENNVAX-B and Inovio expects that the HVTN will initiate this additional Phase I clinical trial before year end.
In a third trial, initiated in 2009, Inovio's collaborators at the University of Pennsylvania began enrolling adult HIV-infected patients undergoing therapy to assess the use of PENNVAX-B DNA vaccine without electroporation in a therapeutic setting. Inovio continues to advance its pre-clinical work on PENNVAX-GP (against HIV clades A, C, and D, the prevalent strains in Africa and Asia) as a preventative HIV vaccine and this work is funded by a contract from the NIH's National Institute of Allergy and Infectious Diseases with a total potential value of about $23.5 million.
The experimental plasmid codon-optimized NS3/4a DNA vaccine is designed to target chronic hepatitis caused by hepatitis C virus (HCV) infection. The vaccine is being delivered using Inovio's MedPulser DNA Delivery System. The plasmid vaccine is delivered into muscle tissue with the assistance of electroporation with the goal of achieving expression of and T-cell immune responses to the NS3/4A antigen. Enrollment has been completed in this Phase I proof-of-concept study of Tripep's HCV vaccine and additional interim results are expected before year end.