BioWorld International Correspondent

Danish therapeutic vaccine specialist Pharmexa A/S is planning to move its DNA-based HER-2 Autovac pharmaccine for treatment of breast cancer into Phase II trials early next summer, following encouraging data from a Phase I/II trial involving 27 patients with advanced metastatic breast cancer.

"We expect to file in March," CEO Søren Mouritsen told BioWorld International.

The Phase I/II data indicate that the product was safe and well tolerated at all three dose levels; that it was capable of inducing HER-2-specific cytotoxic T cells; and that it exhibited some antitumor activity in severely diseased subjects, as evidenced by transient but significant tumor regression in two patients and stable disease in two others. Additional anecdotal evidence, not reported formally, also supported those observations, Mouritsen said.

Hørsholm-based Pharmexa's AutoVac technology is based on the concept of inducing immunological responses to self proteins that are associated with disease. Autovac breaks normal immunological tolerance by engineering promiscuous foreign epitopes into recombinant versions of the relevant antigen. It is developing both DNA-based pharmaccines, which induce cytotoxic T-cell responses, and protein-based pharmaccines, which induce polyclonal antibody responses. The DNA-based HER-2 pharmaccine comprises a plasmid bearing a human promoter that governs expression of a HER-2 gene containing two T-cell epitope inserts derived from Clostridium tetani.

Preclinical development of a protein-based version of HER-2 Autovac is nearing completion, Mouritsen said, and the company plans to commence a Phase I/II trial in the U.S. in February or March. It expects to report results late in 2003 and to progress the two products in parallel. "We are now in a process where we are seeking a partner for both projects," Mouritsen said.

Glaxo SmithKline plc, of London, has an option to negotiate a license for the protein-based candidate, which it gained as part of a license agreement under which Pharmexa is using its Drosophila-derived vector-cell production system. That is a nonbinding agreement, however. "If we don't agree about terms or choose not to outlicense after Phase I, their rights have terminated," Mouritsen said.

Meanwhile, Pharmexa also gained a milestone payment from a separate program, a research collaboration on Alzheimer's disease with Danish pharmaceutical firm H. Lundbeck A/S, of Copenhagen. The companies are using Autovac to develop a protein-based pharmaccine that elicits an antibody response against an undisclosed target supplied by Lundbeck. They have now established proof of concept in animals, and the program is expected to progress to human trials in 12 to 18 months, Mouritsen said.