BioCancell is focusing on the development of its leading product - BC-819, a plasmid comprised of the H19 gene regulatory sequences that drive the expression of Diphtheria Toxin A (DTA). The implementation of the Patient-Oriented Targeted Therapy approach using BC-819 means verifying that the patient's tumors are expressing high levels of H19, then administering the drug to achieve the targeted destruction of tumor cells without affecting surrounding normal tissue.

Two BC-819-based delivery approaches have been developed. The first is for bladder cancer wherein DTA-H19 is mixed with a transfection agent (to facilitate entry of BC-819 molecules into the cancer cells) for bladder instillation. The second BC-819 approach is for advanced stage cancers such as pancreatic, ovarian, and liver carcinomas in which plasmid DNA is injected directly into the tumor or instilled into the peritoneal cavity. Different routes of administration are employed, according to tumor type (intravesical administration for bladder cancer, intratumoral injection for pancreatic and hepatocellular carcinoma, intraperitoneal administration for ovarian cancer with ascites, and hepatic artery infusion for liver metastases). In addition, formulations for systemic administration are under development for use in combination with intratumoral or hepatic artery infusions and other oncotherapeutic agents.

BC-819 has also demonstrated potential with respect to combination therapy. Even in cells that produce small amounts of H19 regulatory RNA, BC-819 has been shown to act to reverse the resistance of the cancer cells to chemotherapeutic agents. Moreover, in BioCancell's therapeutic approach, the plasmid being used to synthesize DTA does not incorporate into the genome of the host. It is believed that this has significant advantages over gene therapy platforms for cancer that depend on a "genetic correction" strategy.

Animal Efficacy & Toxicity Studies

From 2000-2005, Professor Hochberg's research team conducted extensive animal efficacy studies in BC-819. The plasmid was introduced into the bladders of bladder-carcinoma carrying rats (orthotropic model) and mice (heterotopic model), and significant tumor growth inhibition was observed after treatment.  
Between 2006 and 2007, toxicology studies were conducted in rats and mice, in accordance with Good Laboratory Practices Regulations. The studies included repeated administrations of BC-819 at increasing dosages. The dosage given to the animals was higher than the expected equivalent human dosage. No gross pathological findings were evident in the intravesical administration study, and mild to moderate side effects were evident in the intraperitoneal administration study. The studies established the safety of the drug at the examined dosages. Additional toxicology studies in 2008 showed no observable adverse affects at a dosage of at least 10mg per kilogram of body weight (for comparative purposes, participants in the Phase IIb bladder cancer trial of BC-819 receive 20mg doses).