Inovio at ASGT 9th Annual Meeting

Inovio Biomedical Corporation has announced that the focus on the company's technology at the American Society for Gene Therapy's (ASGT) 9th Annual Meeting demonstrated the potential of electroporation for delivering gene-based treatments in humans.

Presentations relating to six pre-clinical studies and a clinical trial employing the company's MedPulser^® DNA Electroporation System were made by Inovio representatives, Vical Incorporated, and the University of South Florida in conjunction with H. Lee Moffitt Cancer Center & Research Institute (Moffitt).

In general, these studies indicated that the use of Inovio's non-viral electroporation technology to deliver therapeutic DNA demonstrated statistically significant levels of gene expression and immune response in a safe and tolerable manner, indicating its promise as an alternative to viral and other non-viral DNA delivery methods.

The process of electroporation uses short electrical field pulses to temporarily open cell membranes so that therapeutic DNA can enter target cells.

Once inside the cells, this DNA may then elicit the production of proteins to stimulate an immune response or provide therapeutic gene expression.

The presentations at the ASGT meeting featured results relating to the use of Inovio's technology for delivering different DNA vaccines and other gene-based therapeutics designed to treat cancer, infectious diseases, and protein-deficiency diseases.

"Electroporation has demonstrated the ability to enhance immune responses to DNA vaccines," stated Vijay Samant, president and CEO of Vical.

"We continue to use Inovio's electroporation technology in our Phase 1 gene-based IL-2 trial for melanoma and are exploring its potential for other therapeutic DNA vaccine applications."

Vical has an exclusive license to use Inovio's MedPulser^® DNA Electroporation System for a DNA plasmid encoding IL-2 for melanoma, a non-exclusive license for DNA vaccines designed to treat HIV and CMV, and an option to license the technology to deliver antigens relating to other infectious diseases.

"We were pleased to see our DNA electroporation technology broadly displayed at such an important scientific conference," said Avtar Dhillon, MD, president and CEO of Inovio.

"Growing evidence shows that electroporation has the potential to enable or enhance the ability of DNA vaccines to generate clinically relevant immune responses and the ability of gene-based therapeutics to treat protein-deficiency diseases such as hemophilia."

"Highlighting positive results from a human study represents a milestone for Inovio and our proprietary delivery platform."

"Our goal is to establish electroporation as a preferred method of DNA delivery and to ensure Inovio's technology is a widely accepted method for commercializing DNA therapy."

The following is a summary of the presentations made by Inovio and collaborators at the ASGT meeting:

- "Electroporation-Based Gene Therapy," part of a workshop, "Non-Viral Gene Therapy"

Richard Heller, PhD, University of South Florida, professor of molecular medicine

Interim results of a Moffitt-sponsored Phase I clinical trial delivering plasmid DNA encoding a cytokine, interleukin-12, into tumor cells to mount an immune response against malignant melanoma were presented by Dr. Heller, a co-researcher with Dr. Adil Daud, principal investigator of the study and an oncologist at Moffitt and the University of South Florida, College of Medicine.

With 15 patients treated to date, results indicate that electroporation-mediated gene delivery was well tolerated, reproducible and without any dose limiting toxicity.

The study showed efficient expression of IL-12 by the plasmid DNA, with demonstrable immune responses.

Prior pre-clinical studies conducted by Heller and his team found that electroporation of IL-12 plasmid also resulted in IL-12 expression in the tumor and an 80 percent complete regression of a very aggressive melanoma in a mouse model.

Based on an assessment of international, peer-reviewed scientific publications, Inovio believes this is the first-ever study using electroporation to deliver a gene-based treatment in man.

- "Overview of Gene Vaccines"

Alain P. Rolland, Pharm.D., Ph.D., Vical, senior vice president of product development

- A study in rabbits indicated that electroporation enhances the onset and magnitude of antibody production against an encoded cytomegalovirus (CMV) antigen in the company's CMV vaccine program.

- A study demonstrated that vaccination by DNA electroporation enhances anthrax lethal toxin neutralizing antibody production by several orders of magnitude.

- A study in rabbits indicated that plasmid DNA is cleared from injected muscles after intramuscular injection followed by electroporation and risk of integration into the host genome is negligible at 60 days.

- "Industrial Liaison: Clinical Developments in Gene Vaccines" - workshop

Michael Fons, PhD, Inovio's executive director, corporate development

Dr. Fons spoke about clinical electroporation and reviewed the pre-clinical and regulatory steps needed to begin clinical evaluation of plasmid delivery with Inovio's proprietary technology.

- "Protection Against In Vivo Tumor Growth after Electroporation-Enhanced DNA Vaccination with the Hepatitis C Virus Non-Structural 3/4A" - poster presentation

Rune Kjeken, Gustaf Ahlen, Jonas Soderholm, Torunn Tjelle, Iacob Mathiesen, and Matti Sallberg

A study conducted with Tripep AB of Sweden indicated that electroporation enhanced cellular immune responses capable of eliminating HCV-antigen expressing cells.

Results indicated that immunization without electroporation was ineffective. The company believes these results validate the concept of electroporation-augmented therapeutic vaccination against hepatitis C virus infections.

The two companies are aiming to initiate a phase I clinical trial using this vaccine by the end of 2006.

- "DNA Vaccines: Induction of Humoral and Cellular Responses Via Skin or Muscle Immunization Enhanced by Electroporation" - poster presentation

Lei Zhang, Georg Widera, Susan Bleecher, and Dietmar Rabussay

This presentation summarized a study that demonstrated the capability of certain methods and devices, which are proprietary to Inovio, to elicit powerful immune responses with either skin or muscle as the target tissue.

Immunization via skin electroporation can be performed non-invasively, which affords potential advantages over invasive muscle electroporation.

- "Feasibility of Cutaneous Gene Therapy Using a Factor VIII Gene and a Marker Gene in Factor VIII-Deficient Mice by Non-Invasive Electroporation" - poster presentation

Lei Zhang, Amy Goldbeck, Hongbo Lu, Edward Nolan, Dietmar Rabussay, and Steve Fakharzadeh

This presentation described a preclinical study conducted in collaboration with the University of Pennsylvania showing that injection of DNA encoding the blood clotting factor VIII (FVIII) into the skin of hemophilic mice gave rise to the expression of the FVIII gene.

This confirms previous results indicating that electroporation-enhanced DNA delivery may be an attractive method of DNA delivery for the treatment of genetic diseases amenable to plasmid DNA-based gene therapy.