Peptech, Domantis in new cancer target development

Sydney biotech Peptech (ASX:PTD) has signed up with its 36.1 per cent owned UK partner Domantis to develop a domain antibody (dAb) for the cancer target identified by its Sydney joint venture partner Biosceptre.

Peptech and Biosceptre plan to develop the dAb as a potential diagnostic, therapeutic, drug-delivery vehicle and imaging agent for solid tumours.

In the past six months, Peptech has released the results of preclinical trials of a monoclonal antibody targeting Biosceptre's antigen, which remains a closely guarded secret while the partners swathe it in protective patents.

Peptech and Biosceptre have previously announced they are developing a topical cream to treat common skin cancers, based on a monoclonal antibody (mAb), and have confirmed that the mAB reliably detects ovarian tumours.

Almost in passing, they have mentioned its potential diagnostic and therapeutic applications for various other tumours.

Make that all solid tumours, according to Peptech executive chairman, Mel Bridges. "Of all the projects I've looked at in various biotech companies over the years, this is the one that really got me excited," he said.

"We've been reasonably secretive about the target, but it's present on the surface of every solid tumour we have tested. It's the first marker I know of that is found across almost all cancers -- the only exceptions we currently know of are leukaemias and lymphomas.

"We know that the monoclonal antibody definitely binds to its target, so it definitely works diagnostically.

"We've had very encouraging results in therapeutic trials in volunteers with skin cancers, which are the easiest of all cancers to excise surgically, and we're encouraged at the potential of mAb-based treatments for a much wider range of solid tumours."

Highly selective

Because the 'universal antigen' is present only on the surface of solid tumours, the mAbs provoke a highly selective inflammatory reaction. In the skin-cancer trials, it killed only the tumour cells, leaving healthy cells intact. Healthy cells rapidly recolonise the site, leaving almost no scarring.

If that result translates to internal solid tumours, the joint venture partners have a potential generic cancer drug on their hands: something as broadly applicable as the new wave of angiogenesis inhibitors, which starve and asphyxiate tumours by blocking the growth of new blood vessels.

Bridges said the specificity of the mAb -- or the new domain antibody being developed by Domantis -- could also be exploited to deliver cytotoxic drugs to enhance tumour killing.

The antibodies can also be linked to radioisotopes and used to image primary tumours, or to highlight secondary, metastatic tumours forming in other organs like the liver or brain. Whole-body scans could reveal 'hotspots' indicative of early-stage primary or metastatic cancers.

Not only is the antigen apparently present in all solid human tumours, Bridges said, it is also highly conserved across mammal species, so antibody therapeutics, diagnostics and imaging agents could be used in veterinary medicine as well.

Why develop a domain antibody when the company already has mAbs that do the job well?

Bridges said the dAb would be developed in parallel with the mAb agent. "What we've seen in comparative tests between our TNF [tumour necrosis factor] monoclonal antibody and our TNF dAb, is that the dAB is about half the size.

"It can get into tissues that the mAb can't, which is a potential advantage in imaging. We can also adjust the half-life of dAbs to the particular application, because they're incredibly flexible to work with. And because dAbs can be made more cheaply, they'll be very competitive with monoclonals.

"We're definitely thinking about using the antibodies to deliver cytotoxic drugs, and it would be very straightforward to develop them as tumour-imaging agents."

Bridges said Domantis was continuing to impress the pharmaceutical industry with its proprietary dAb technology, and had clearly demonstrated their versatility as potential therapeutic agents for a wide range of medical conditions.