After 17 years at CSL, seven at Millennium Pharmaceuticals in the US and a couple overseeing the merger of the struggling Meditech Research with Alchemia in 2006, it was going to take quite an interesting offer to draw Dr Ian Nisbet out of the consulting world and into another CEO role.

In January this year, it was the venom-derived peptide company Xenome that managed to tempt him back. Since joining the company, Nisbet has had the pleasure of announcing a nice little investment from venture capitalists and good results from a Phase II trial for the relief of chronic pain in cancer patients.

Like Meditech, Xenome has had a bit of chequered history, with internal divisions and long delays in early stage trials due to problems with patient recruitment, but in the last year it has raised over $16 million in equity and investment.

Nisbet has put plans for an IPO on hold until the market rights itself, but in the meantime has raised US$6 million from Melbourne biotech investment group GBS Venture Partners and announced the good trial results at a world congress on pain in Glasgow in late August.

Xenome was founded by well-known scientists Richard Lewis, Paul Alewood and Queensland chief scientist Peter Andrews, all then from the University of Queensland, along with CSIRO’s Roger Drinkwater. Lewis and Drinkwater are still with the company – Lewis is the chief scientific officer and Drinkwater the vice president of R&D – and a chief medical officer, Dr Wendy Martin, was recruited last year and is based in San Diego.

The original concept that started the company was that venoms, particularly venoms from cone snails, also called cone shells, and other venomous creatures were a good starting point for pharmacologically active agents, Nisbet says.

“When you think about it, these are molecules that have over evolutionary time been designed to act at very small doses, by injection,” he says. “They have exquisite activity on fundamental molecular targets to induce paralysis. Conceptually, as a starting point for doing drug discovery, venoms seem a good place to start.”

Cone shell venoms were the original molecules of choice, as unlike spider and snake venoms, which are large peptides and are complex to make synthetically, cone shell venom peptides are quite small.

“They are generally less than 20 amino acids in length,” Nisbet says. “The concept was that we have a cornucopia of venomous creatures on our doorstep, let’s go through and identify smaller molecular-weight peptides, make libraries of these peptides and start screening them against interesting targets.”

Xenome now has a library of more than 2000 synthetic peptides, covering about 50 different species of cone shells. One venom peptide of interest was found to have activity against the norepinephrine transporter (NET), with the inhibition of this transporter found to elevate levels of norepinephrine in the spinal cord, modulating pain signals from the brain.

This native peptide served as a starting point for a synthetic analogue that became Xenome’s lead drug candidate, Xen2174.

“It’s about 1.14 kDA so it is small, 13 amino acids, and has two disulphide bridges,” Nisbet says. “This is a tightly constrained, three dimensional structure and that gives it not only a clear structure for a pharmacophore but it also provides some stability over and above a linear peptide.”