VGX™ Pharmaceuticals

VGX is developing Growth hormone Releasing Hormone (GHRH) technology for a number of indications including cachexia in cancer and HIV patients as well as for age-related disorders. The underlying technology was developed in the laboratories of Dr. Robert Schwartz, Dr. Ruxandra Draghia-Akli, and their colleagues during their time in the Department of Molecular & Cellular Biology at Baylor College of Medicine (BCM).

VGX™ GHRH is a naturally occurring molecule with similar characteristics and activity in humans and animals. GHRH is a key potentiator of the GHRH - Growth Hormone (GH) - Insulin like growth factor (IGF-1) axis and studies in different animal models and humans have shown that GHRH has both direct and indirect functions in development, muscle metabolism and maintenance of hematological and immune status under physiological and pathological conditions.

A significant advancement in the use of GHRH to treat conditions such as cachexia or anemia, to optimize development, or to stimulate immune function has been the creation of myogenic plasmid vectors that express GHRH. These species-specific DNA plasmids can be injected into a skeletal muscle, are not integrated into the cell’s genome and are expressed by muscle cells for desired periods of time. Plasmid uptake can be enhanced by electroporation. Studies demonstrated expression for up to two years in large animal models such as cows and pigs. No repeat treatments are necessary within this time period. This innovative method allows GHRH to be naturally produced and maintained under physiologic feedback regulation.

Pre-clinical Testing in Animal Models: VGX has developed Plasmid-based GHRH technology.
	Extensive testing has been conducted for safety and efficacy in several food and companion animal species (cattle, pigs, dogs, cats and horses), as well as laboratory animals (mice and rats).
	Long-term hematological parameters and quality of life were improved after a single plasmid GHRH administration in dogs with spontaneous malignancies or geriatric disabilities.
	Preliminary studies on dogs and cats with renal failure showed that the treatment resulted in correction of anemia, while renal function was maintained.
	In directly treated cattle, plasmid-mediated GHRH supplementation stimulates T cell and natural killer cell numbers that may be associated with an improvement in immune function, nutritional and health parameters.
	The clinical consequences in cattle were a significant reduction in morbidity and mortality as well as improved body condition scores as compared to control animals.
	Recent results in rats, pigs and cows have also demonstrated that when pregnant animals are administered plasmid-mediated GHRH supplementation, they gave birth to healthier offspring.
	Offspring of plasmid-mediated GHRH treated pigs demonstrated a decrease in mortality of 57% compared to offspring from untreated animals.
	Morbidity in offspring from treated animals was substantially reduced suggesting the potential for discontinuation of routine antibiotic treatments.
	Horses with chronic arthritis/laminitis had significant improvements in body condition, metabolic profiles and resolution of lameness.
Potential GHRH Applications in Humans: Extensive data in the literature and Phase I/II human clinical trials using protein GHRH formulations support the following applications for plasmid-based GHRH hormone therapy:
	Management of cachexia and anemia associated with cancer and its therapies.
	Management and supportive therapy for complications of HIV/AIDS such as lypodystrophy.
	Age – related sarcopenia / cachexia, loss of cognitive function, and sleep disorders in elderly.
	Age-related diastolic dysfunction.
VGX is currently pursuing a development program for a cancer cachexia product, VGX-3200, for which it filed an IND in February 2008.