BIO profile: Hit and hit again for Bionomics

Adelaide-based biotech Bionomics has announced better than expected preclinical data for its lead cancer drug candidate BNC105.

Dr Gabriel Kremmidiotis, Bionomics' vice president of discovery research, told an American cancer research conference that preclinical findings revealed BNC105 had even greater capability to regress tumours than initially expected. The mouse studies showed that following two cycles of BNC105 treatment, 14 per cent of mice carrying human breast cancer became tumour free.

"Although we have previously seen BNC105 stopping tumour growth or causing tumour regression, in our latest dose optimisation experiments we saw for the first time that BNC105 caused some tumours to completely disappear", Kremmidiotis said.

In studies involving 64 tumour-bearing animals, four injections of BNC105 produced significant suppression of tumour growth or regression in 45 per cent of the animals and an additional 14 per cent of the animals were cleared of their tumour burden with the tumours not re-appearing, he said. In this 70-day study, BNC105 was administered on days 1, 8, 29 and 36.

"In addition, more recently we have obtained evidence that BNC105 is likely to be active against more than one tumour type," he said. The studies showed that BNC105 exhibited very high potency in disrupting blood vessels in a model of human colon cancer.

Bionomics' CEO Dr Deborah Rathjen said phase I clinical trials will begin later this year, following its anticipated Investigational New Drug (IND) submission to the US Food and Drug Administration (FDA).

BNC105 is a new type of drug called a vascular disruption agent (VDA) that acts to rapidly shut down the blood supply within a tumour. It thereby "starves" the tumour of the oxygen and nutrients it needs to survive.

VDAs have significant clinical potential in the treatment of cancer, as they may potentially be applied across a very wide variety of cancer types, including colon, lung and breast cancers.

Company background

In addition to its work on BNC105, Bionomics has also joined forces with Australia's new Co-operative Research Centre (CRC) for Cancer Therapeutics, the only drug discovery partner in the venture and a move that Rathjen says will fill a critical need in the discovery of new cancer drugs and, importantly, the ability to move them from proof-of-concept to the clinic.

"There has been a significant gap in Australia so the CRC brings together all of the key players that are able to move new drug candidates forward," Rathjen says. "Bionomics has a number of well-validated drug targets that have come out of our genomics activities and we are hoping that the Cancer Therapeutics CRC will give us the opportunity to supplement our cancer pipeline with new drug candidates."

Rathjen has led Bionomics since mid-2000, following a highly successful time at Peptech, where she helped develop one of its anti-TNF drugs. Since then, Bionomics has made a number of acquisitions, including a European subsidiary called Neurofit SA that has a broad capability in pre-clinical central nervous system research.

"We also acquired a Melbourne-based company called Iliad Chemicals which is now fully integrated into Bionomics," she says. "Their proprietary chemistry is called MultiCore. Those two acquisitions, combined with Bionomics' proprietary platforms, which are called IonX - for CNS drug discovery and ion channel drug discovery - and Angene, which is our cancer drug discovery platform, really underpin the company and give it great strength in terms of identifying new molecules with some potential through to moving drug candidates rapidly forward."

It was a combination of the company's proprietary Angene platform and Iliad's focused library of compounds, based around a known molecule with vascular disruption activity, that provided the genesis of BNC105, she says.

"BNC105 is a very impressive anti-cancer agent - it specifically targets the tumour vasculature, gets in there and starts to disrupt it - but it is also able to provide a double hit through a direct cytotoxic action on the tumour cell.

"That's why we call it a 'hit-and-hit-again' drug. It has this huge specificity, about a hundred-fold or greater for tumour blood vessels relative to normal blood vessels, and then once it's trapped there in the tumour it's able to provide a second hit with a direct cytotoxic action. Then there is rapid tumour death.

"We've seen regression and we've seen animals cured of their tumours. In all of my years in biotech it has been the most impressive anti-cancer agent that I've seen in the pre-clinical setting."

It has also proved a remarkably fast process, with the Iliad acquisition completed in July 2005, the drug candidate identified in April 2006, a pre-IND meeting held with the FDA in January 2007 and plans afoot to submit the IND in the third quarter of this year.

It has meant putting another drug candidate for the BNO69 angiogenesis gene on the backburner. The new CRC venture, however, should assist in further developing this target, Rathjen says, and the company is still working in other fields.

"In our CNS platform we have a focus on ion channels. We are still in the process of selecting our drug candidates there but we are on track for nomination of drug candidates in 2007. We have very exciting lead compounds there with good bioavailability.

"We have also identified some diagnostic applications from our epilepsy gene discovery and these were in the identification of different forms of childhood epilepsy. We've licensed those genetic tests to Athena Diagnostics, a specialist diagnostics company in the US."

It has also secured a deal with a Danish antibody company called Genmab. "We had a group of eight very well-validated antibody targets, which as a small molecule company we couldn't develop ourselves, so we out-licensed those last year to Genmab in return for an upfront payment, future milestone payments on pre-clinical and clinical milestones and a royalty on any products sold. It's a very nice deal for Bionomics."

Bionomics will exhibit as part of the Australian Pavilion at BIO 2007 in Boston.