Proprietary Liposomal Technology

Transave's proprietary liposomal technology is designed specifically for delivery of pharmaceuticals to the lung and provides for potential improvements to the conventional inhalation methods of delivering drug to the pulmonary system. Transave's proprietary technology provides potential advantages over conventional methods of inhalation therapy in terms of efficacy, safety and patient convenience.

Underpinning these potential advantages are the following four factors:

Sustained delivery of drug to the lung – The liposomes provide for a relatively sustained release of drug to the lung, which may be important in treating certain bacterial infections that have a significant pulmonary component. Maintenance of anti-bacterial levels in the lung above the minimum inhibitory concentration (MIC) for prolonged time periods is an important component in the effectiveness of antibiotics; the area under the concentration curve (AUC) reflects drug exposure;

Endogenous lipid excipients - The lipid components of Transave's compounds are the same as those in the lung's pulmonary surfactant, which may ensure a more natural metabolism and clearance than polymeric drug delivery systems. This may reduce the chance of adverse reactions;

High efficiency encapsulation – Transave's liposomes are designed to encapsulate very high concentrations of drug into relatively small liposome structures. This efficiency allows Transave's compact, drug-laden liposomes to physically penetrate bacteria-generated mucoid biofilms in pre-clinical models. Importantly, these liposomes deliver drug effectively near the bacteria as drug is released because of specific lytic factors that exist inside the biofilms;

Charge-neutral liposomes - Transave's liposomes can be charge neutral, which may be an important factor in penetration of any patient mucus and bacterial biofilm. A positive charge, such as that naturally found with cationic antibiotics, can prevent the penetration of these molecules into the mucus and bacterial biofilm, due to the natural negative charge of these biological surfaces.

Transave's liposomal technology can be used for the successful delivery of low molecular weight products like classic pharmaceuticals as well as high molecular weight compounds such as peptides, proteins and genes. Transave's unique lipid-based delivery systems are not dependent on the inhalation device and can be administered either as a nebulized aerosol spray or as a dry powder.

A goal of localized targeting of drugs using this unique delivery system is to reduce systemic toxicity by minimizing the exposure of non-disease sites to the drug. Another potential benefit may be enhanced efficacy as a result of larger amounts of the drug being delivered directly to the site of disease.

Liposomes are microscopic artificial sacs that can consist of a single membrane bilayer, or they can be onion-like structures characterized by multiple membrane bilayers, each separated from the next by an aqueous layer. The bilayer is composed of two lipid monolayers having a hydrophobic "tail" region and a hydrophilic "head" region. The structure of the membrane bilayer is such that the hydrophobic (nonpolar) tails of the lipid monolayers orient toward the center of the bilayer, while the hydrophilic heads orient toward the aqueous phase. In a liposome drug delivery system, the drug is trapped in the liposome and then administered to the patient to be treated. Water soluble drugs would be located in the liposome's aqueous core, while hydrophobic/lipophilic drugs may be found in or associated with the lipid bilayer.

The company's proprietary liposomal technology provides for a sustained release of drug to the lung, which may be important in treating certain bacterial infections that have a significant pulmonary component.