Zenyth licence to boost antibody targets

Zenyth Therapeutics (ASX:ZTL), formerly Amrad, has taken a licence from Massachusetts-based Dyax Corp, to use the US company's proprietary phage display libraries to develop antibody therapeutics for inflammation and cancer.

Zenyth CEO Dr Andrew Nash said the agreement provided his company with a powerful new tool for developing human antibody-based therapeutics. He said Zenyth would apply the technology immediately to existing and new projects, and would soon make further announcements about these projects.

Phage display technology offers substantial advantages over conventional methods of developing human antibody therapeutics, according to Nash.

"There are three fairly standard platform technologies for generating therapeutic human antibodies, and we wanted to have at least one operating in-house for current and new targets," he said.

"We've previously used the Medarex UltiMAb human antibody platform, but we've had some experience with phage display technology through Cambridge Antibody Technologies, and it's the most flexible of the technologies out there."

Medarex uses transgenic mice expressing human antibody genes to generate fully human monoclonal antibodies. The third approach is to 'humanise' antibodies raised in mice, to minimise the risk of the patient's own immune system attacking them as alien, and triggering life-threatening anaphylactic shock.

With phage display technology, hypervariable antibody genes from human B lymphocytes are cloned into bacteriophage viruses, which 'display' the expressed antibodies at the end of their rod-shaped particles. A phage display library potentially contains a trillion unique antibodies, enough to complement any molecular shape found in nature. Phages whose monoclonal antibodies make the strongest 'matches' with the target antigen then under successive rounds of mutation and selection to increase their specificity.

Nash said both the Medarex and humanisation techniques involve generating antibodies to the target antigen in mice -- failure results in an impasse.

"With phage-display technology, antibody selection for the target antigen is done in vitro, with no mouse involved," he said. "It's quite rare to get an animal antibody that will cross-react with the equivalent human antigen. With phage display, you can develop and test surrogate antibodies in species like mouse, pig or monkey, and get indications of toxicology and efficacy before moving to test the human antibody in humans."

Asked whether there were still market opportunities amid intense international competition to develop anti-inflammatory mAbs, Nash said it all depended on the quality of the target antigen, and the therapeutic response obtained. "There are certainly a lot of candidates out there, but not all of them are supported by quality preclinical data."

Nash said Zenyth had large amounts of data on the GM-CSF receptor as a proprietary target, and is "very confident' of its commercial potential. Zenyth was moving through the manufacturing process with leading Swiss-based mAb manufacturer Lonza Biologics.

"Our other lead program is with interleukin-13 (IL-13) in collaboration with Merck, for the asthma market," he said "Asthma is poorly covered by current anti-inflammatory therapies."