OTHER CANCER PROGRAMS
In a 2003 amendment to our prior agreement, Merck acquired options for rights to use our core DNA delivery technology for three cancer targets. The two disclosed targets were human epidermal growth factor receptor 2, or HER-2 and carcinoembryonic antigen, or CEA.In 2005, Merck initiated a Phase 1 clinical trial of a DNA cancer vaccine based on our DNA gene delivery technology that uses pDNA encoding HER-2 and CEA. The Phase 1 trial will evaluate the safety, tolerability and immunogenicity of the vaccine.
In 2004, we granted an exclusive license to Merial, a joint venture combining the animal health businesses of Merck and sanofi-aventis, for use of our core DNA delivery technology in a vaccine to protect dogs against melanoma. Under the agreement, Merial is responsible for research and development activities. The Merial canine melanoma vaccine received conditional approval from the United States Department of Agriculture, or USDA, in 2007.
IL-2/EP
In July 2005, we initiated a Phase 1 study which incorporated the enhanced delivery of plasmids encoding human IL-2 for patients with recurrent metastatic melanoma. Intravenous delivery of IL-2 protein is approved as a treatment for metastatic melanoma and renal cell carcinoma, but frequently causes severe systemic toxicities. The novel treatment approach being studied in this trial involved direct injection into a tumor lesion of pDNA encoding IL-2 followed by electroporation, a process involving the application of electrical pulses to targeted tissues to potentially open pores in cell membranes and allow greater transfer of material into the targeted cells. The pDNA is designed to cause cells within the tumor to produce high levels of IL-2 protein locally and stimulate the immune system to attack the tumor without the associated systemic toxicities.
Treatments in the trial were administered once a week in two four-week cycles, with each cycle followed by an observation period. The initial dose-escalation phase of the trial enrolled three subjects each at doses of 0.5 mg, 1.5 mg and 5 mg delivered to a single tumor per subject, with a final group receiving 5 mg in each of three tumors per subject. Additional subjects were treated at the highest dose of 5 mg per tumor in up to three injectable tumors.
In June 2007, we announced interim data on 19 subjects from the trial demonstrating that intratumoral delivery of pDNA encoding IL-2 into melanoma tumors, followed by electroporation, was administered safely following sedative premedication. No serious adverse events related to the study drug or to the administration procedure were reported and the treatment was well-tolerated. The majority of related adverse events were localized to the treatment site, with the most frequent being mild injection site pain.
Individual tumor responses were seen in 12 of 39 (31%) evaluated tumors after injection of different escalating doses (0.5 to 5 mg per tumor). Treated tumors (7 of 18, or 38%) showed local responses more frequently than did untreated tumors (5 of 21, or 24%). No overall clinical responses by standard RECIST criteria were observed among the 19 subjects evaluated following one or two cycles of treatment. Two subjects (11%) showed activity in distant, untreated tumors, including one subject showing shrinkage and disappearance of lung tumors.
The primary objective of the IL-2/electroporation study was to evaluate the safety and tolerability of electroporation. We believe the interim results of the study support electroporation’s potential value in treating advanced cancer or other serious diseases. However, the need for premedication would limit the use of the current electroporation technology in less serious disease applications. We currently have no plans to pursue further development of our IL-2/electroporation product candidate.