TECHNOLOGY

Bio-Path’s neutral lipid delivery technology provides systemic distribution of nucleic acid drugs throughout the human body through simple intravenous transfusion. Bio-Path’s delivery technology applies to both double stranded (siRNA) and single stranded (antisense) nucleic acid drugs. This technology has the potential to revolutionize the treatment of cancer and other diseases where the targets of disease are well characterized. The reason is because the neutral lipid delivery capability enables systemic delivery of nucleic acid drugs to diseased cells, something no other technology can do.

Delivery of siRNA Molecules: Small interfering RNAs, or siRNAs, are the molecules that mediate RNA interference (“RNAi”) and interfere with the process of producing proteins inside cells. The siRNA are short double stranded nucleic acid molecules that can be synthesized chemically and introduced into cells, creating enormous possibilities for using siRNAs as drug candidates to treat major diseases including cancer. Introduction of a double stranded nucleic acid molecule specific to a target disease-causing protein conditions cellular machinery to shut-down production of that target protein. Potential advantages of siRNA drugs include:

The ability to target virtually any disease-causing protein where the targets of the disease are well-characterized.
With siRNA therapeutics, it is possible to block the production of disease-causing proteins, which provides improved capability for disease control.
Because siRNA are designed to target a specific disease-causing protein, the potential for other interactions that might cause toxicity is minimized.

However, the greatest challenge facing successful deployment of siRNA drugs has been lack of technology that can deliver the double stranded nucleic acid siRNA molecules to the target diseased cells. Bio-Path’s patented delivery technology solves this problem by employing DOPC neutral lipid formulations to incorporate the siRNA into liposomes. These liposomes are inert in the body, incorporate the siRNA with high efficiency and form nano-sized particles that can migrate inside tumors.

Testing of Bio-Path’s delivery technology in animals has demonstrated a 10-30 fold advantage in delivering siRNA to target cancer cells.

Delivery of Single Strand Nucleic Acids: Similar to siRNA, a second class of RNAi drugs involving single strand nucleic acid molecules has been developed by the pharmaceutical industry. Introduction of a single strand nucleic acid molecule specific to a target disease-causing protein blocks the ability of the cellular machinery to produce that target protein. However, delivery of single strand nucleic acid molecules to target cells has been a challenge that has limited pharmaceutical industry development of effective drug products employing this technology. Bio-Path has patented delivery technology that solves this problem by employing a DOPC neutral lipid formulation for single strand molecules that incorporate into liposomes.

Tumor Targeting of Liposomes: This new technology involves delivery of antisense technologies and FAK siRNA. Tumor targeting will enhance the Company’s liposome delivery technology by adding vectors to the liposomes targeted to a receptor that is specifically over-expressed on a majority of solid and hematological tumors and on eighty percent (80%) of metastatic epithelial tumors. The Company believes this liposome tumor-targeting technology for antisense and FAK siRNA delivery is a highly promising strategy for treating primary and metastatic cancers.

The historical perspective of cancer treatments has been drugs that affect the entire body. Advances in the past decade have shifted to treating the tumor tissue itself. One of the main strategies in these developments has been targeted therapy, involving drugs that are targeted to block the expression of specific disease causing proteins while having little or no effect on other healthy tissue. Nucleic acid drugs, specifically antisense and siRNA, are two of the most promising fields of targeted therapy. Development of antisense and siRNA, however, has been limited by the lack of a suitable method to deliver these drugs to the diseased cells with high uptake into the cell and without causing toxicity. Bio-Path’s currently licensed neutral-lipid based liposome technology is designed to accomplish this. Studies have shown a 10-fold to 30-fold increase in tumor cell uptake with this technology compared to other delivery methods. The Company’s first drug with this delivery technology is scheduled to commence a Phase I clinical trial in the fourth quarter 2009.

The new liposome tumor targeting technology being licensed will be developed as an extension of the Company’s current delivery technology, with a goal towards more powerfully focusing delivery of the antisense and FAK siRNA cancer treatments to the tumor tissue. Adding a vector to the liposome that targets a receptor that is highly expressed on the surface of tumor cells is expected to drive uptake of the liposomes into the tumor tissue, enhancing relative deposition in the target tumor tissue. In animal studies conducted at
M. D. Anderson Cancer Center, researchers demonstrated an ability for vector targeted neutral lipid-based liposomes to increase transfection efficiency and siRNA molecule uptake 5 to 8-fold into cancer cells compared to those of untargeted liposomes and controls. These efficiencies are in addition to the delivery efficiencies noted above from the core neutral lipid-based liposome delivery technology.