BioWorld International Correspondent
Danish therapeutic vaccine developer Pharmexa A/S disclosed that GlaxoSmithKline plc holds an exclusive option to negotiate a license for its AutoVac HER-2 Protein project for breast cancer. GlaxoSmithKline, of London, has held this position since June as part of a licensing agreement involving its Drosophila-derived vector-cell production system.
Horsholm-based Pharmexa has decided to press ahead with this expression system in its advanced preclinical and clinical development work. It transferred production of the HER-2 Protein pharmaccine to a contract manufacturer and plans to commence animal toxicology studies this month. Clinical trials are slated to begin early next year. The option will expire following a defined, but undisclosed, period after the completion of Phase I studies. “The idea is if GSK decides to say no’ or if we cannot come to terms, then we are free to license it to a third party,” Pharmexa Chief Operating Officer Birger Borregaard told BioWorld International.
A complementary program, which involves the development of an AutoVac HER-2 DNA therapeutic vaccine, has entered Phase I/II clinical trials, but is not yet partnered out. “We are in discussions, but unless we get a fairly good offer on the DNA side there’s no reason why we shouldn’t wait until Phase II,” Borregaard said.
He said the company evaluated a number of different expression systems as part of the HER-2 Protein project, but the GlaxoSmithKline option proved best for preserving protein structure. “The more we can preserve the tertiary structure, the better the [immune] response we get,” he said.
Pharmexa’s proprietary AutoVac technology is based on stimulating immune responses to self-antigens by circumventing normal tolerance mechanisms. It achieves this by creating recombinant pharmaccines containing the target antigen plus promiscuous foreign epitopes derived from sources such as the tetanus toxoid or the PADRE technology, which the company licensed from Epimmune Inc., of San Diego. They can provoke a range of polyclonal antibody or T-cell responses, depending on the nature of the pharmaccine.
“The immune effector mechanisms we think we can elicit with the protein are quite different from the immune effects we would expect from the DNA,” Borregaard said. The company would expect the DNA-based vaccine to stimulate the production of cytotoxic T lymphocytes that would kill off cancer cells expressing the HER-2 antigen, whereas it expects the protein-based vaccine to elicit the production of antibodies that bind to the HER-2 receptor and inhibit its oncogenic action. “Because they would work synergistically, it would make sense for one [partner] to do both,” he said.