BIO 2012 biotech profile: Bionomics

This feature appeared in the May/June 2012 issue of Australian Life Scientist. To subscribe to the magazine, go here.

Conventional fast-acting anti-anxiety drugs, such as benzodiazepines (Valium), often cause a host of unwanted side-effects, including detrimental effects on memory, attention and motor co-ordination, along with the threat of addiction.

As such, the prospect of an effective anti-anxiety treatment that comes without the attendant side-effects is something that is sure to make heads turn, not least because of the $10+ billion that are spent on anxiety and related conditions worldwide. And turn heads is precisely what Bionomics has been doing thanks to its experimental anti-anxiety compound, BNC210.

In the opening days of this year, the South Australian biotech signed a global partnership agreement with specialty pharmaceuticals company Ironwood Pharmaceuticals to further develop and commercialise the BNC210 compound. This deal alone could be worth as much as US$345 million in milestone payments and royalties, making it potentially the largest deal in Australian biotechnology to date for a phase I asset.

Bionomics was founded in 1999, around the time that many aspiring Australian biotechs took root. Its specialisation is drug discovery and early-stage development, concentrating on small molecule treatments, particularly for cancer and central nervous system disorders.

Heading the company is biotech veteran, Deborah Rathjen, who has been in the boss’ chair since joining the company in 2000 shortly after it was established. Prior to this role, Rathjen has had a long career in the life sciences industry. She got her start as a research scientist, working on the behaviour of cytochromes in anticancer responses and in inflammatory diseases including rheumatoid arthritis and chromes disease.

As a part of her scientific credentials, Rathjen is co-inventor of a patent covering anti-tumour necrosis factor (TNF) antibodies and their use in treating inflammatory conditions. This patent covers the anti-TNF antibody Humira, which is expected to become the highest selling pharmaceutical drug of any class in the world. Thanks to some IP enforcement activities on Rathjen’s behalf, Bionomics now receives a royalty on Humira sales.

For Rathjen, joining Bionomics was “just one of those lucky events that happen in your life sometimes, where a number of people that you’ve worked with form a company,” she says. “I was working at my former company, Peptech, and I got a call out of the blue in relation to Bionomics. It all started from there.”

Rathjen says it was the company’s “forward looking vision” that first attracted her to the role. “Bionomics started as a genomics company. The group that were intimately involved in the company were the only Australians to have participated in the Human Genome Project, and one of the founders was a past chair of the Human Genome Organisation,” she says. “It was in the vanguard of genomics research.”

In modern drug development, it’s becoming increasingly important to have a deep understanding of the genetics of various conditions, Rathjen says. This is especially true in the field of oncology, but a genetic focus can also be beneficial in other fields, including mood disorders.

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Anti-anxiety without the worries

BNC210 is Bionomics’ flagship compound under development for the treatment of anxiety and depression. Early stage trials in animals and healthy volunteers indicate that the drug has the potential to be rapidly acting, non-addictive and free of the side-effects associated with currently marketed drugs. Another trial indicated that the compound may be able to alleviate the symptoms of a panic attack within 10 minutes, compared to an hour for a placebo.

Ironwood Pharmaceuticals, a mid-scale US pharmaceutical company, is gearing up to submit an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) and pursue further clinical trials.

Under the terms of the licensing deal, Ironwood has agreed to fund all trials and be responsible for worldwide development and commercialisation of all BNC210 products, with Bionomics receiving a royalty on sales, along with an upfront US$3 million payment and milestone payments, which together could amount to a total of US$345 million.

“It was very pleasing that we discovered that molecule and had it taken through clinical trials, where we have a very significant global partnership in place for its continued development and commercialisation,” Rathjen says.

According to Bioshares co-owner and co-editor David Blake, the BNC210 compound is perhaps the most promising of the compounds Bionomics has under development. He says there is a good opportunity to release a drug that provides the benefits of major drugs, including diazepam, without the side-effects.

“It’s a good strategy to improve on what’s offered in a particular known market segment, but not necessarily having to reinvent the wheel,” says Blake. “It means there’s a lot of ways in which you can demonstrate efficacy. You don’t have to be the first drug treating a known condition, where the commercial environment is unclear.”

The deal is a significant milestone for Bionomics. It’s a huge deal for a drug candidate that has yet to leave phase I trials. Ironwood appears to be a good match for Bionomics, with it being big enough to handle the trials and further development of BNC210, but small enough to give it the singular attention it needs. And if all works out, the deal could be very lucrative for both companies, particularly thanks to the royalties pouring in to Bionomics.

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Fighting platinum-resistant tumours

BNC210 also isn’t the only horse in Bionomics’ stable. Another compound in advanced development is BNC105, a vascular disrupting agent with potential applications in treating a range of solid tumour types.

BNC105 selectively targets and shuts down blood vessels found in the centre of solid state cancers while leaving normal blood vessels untouched. It has also been shown to have a direct cytotoxic effect on cancer cells including – crucially – platinum-resistant cells.

A number of chemotherapy drugs, including cisplatin and carboplatin, contain platinum derivatives. These complexes are used to cause crosslinking of DNA, and trigger programmed cell death. But cancer cells treated with platinum-based products often develop chemoresistance, to the point where the therapy is no longer cytotoxic.

In laboratory tests, BNC105 has demonstrated a cytotoxic effect on the cisplatin-resistant cancer cell line A2780cis. And in animal trials, the compound reduced tumour growth and increased survival in rates in animals with tumours resistant to platinum-based drugs.

“Furthermore, for those tumours where there’s no resistance to platinum-based drug, we’ve found that BNC105 will combine synergistically with a platinum-based drug to give an even better anti-tumour response,” Rathjen says.

BNC105 is being developed for use in conjunction with a number of anti-cancer regimes, she says. These include chemotherapy as well as biological therapy – drugs like angiogensis inhibitor bevacizumab (Avastin). “In animals it has been shown to work synergistically with Avastin, and also to give very significant benefits when used in combination with radiation therapy as well.”

Bionomics is engaged in an ongoing clinical trial of BNC105 in kidney cancer, and in late March was granted approval from the FDA for a phase I/II trial of the treatment candidate in women with ovarian cancer. The trial is on track to commence this quarter, Rathjen says.

The compound has potential applications in solid tumour types beyond ovarian and kidney cancers, including lung, prostate and breast cancers, melanoma and mesothelioma. “We’re very excited by the potential of BNC105,” Rathjen says.

However, Blake believes the commercial possibilities of BNC105 could be more limited than BNC210 due to the particularities of the oncology sector. “There are different dynamics, different factors that affect the clinical viability and commercial potential for cancer therapies,” he says.

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Chemistry and biology

Bionomics has also been collaborating with Merck Serono since 2008 to develop possible treatments for multiple sclerosis. The partnership involves the development of Kv1.3 blockers. Kv1.3 is a key regulator of effector-memory T-cells. As well as multiple sclerosis, the drug target has potential applications in other autoimmune diseases such as psoriasis and rheumatoid arthritis, and Rathjen says Bionomics is looking at exploring these applications.

Another program under development is Alpha 7, which aims to develop a drug candidate to modulate the alpha 7 nicotinic acetylcholine receptor. This could potentially reduce cognitive impairment in patients with Parkinson’s disease, MS, schizophrenia or ADHD. Rathjen says that in following with its business model, the company will pursue a partner for the Alpha 7 program when the time is right.

Bionomics also has a subsidiary, Neurofit, which is a contract research organisation specialising in peripheral and central nervous system disorders. Rathjen called Neurofit a cash-flow positive business with “a lot of strategic importance for the company.”

According to Blake, one of Bionomics’ biggest advantages is that it is able to be a “chemistry and biology company. They have a capability to discover drug targets and apply chemistry to develop drugs. It’s that throughput capacity that is its strength.”

But the company’s focus on small molecule drugs might also be a source of vulnerability, says Blake. “It’s hard to get a real point of difference with small molecule drugs, where the point of difference can come from a huge improvement on performance.”

Still, Bionomics has added itself to the ranks of second generation antipodean biotechs that have begun to blossom after a decade or more of gruelling product development since they were founded in the 1990s.

The deal with Ironwood will lend Bionomics a welcome cash injection and lighten the load of developing BNC210 under its own steam, allowing it to invest more time and money into other candidates, such as BNC105. Under the steady hand of Rathjen, Bionomics could prove to be another biotechnology success story, and is definitely a company to watch in the years ahead.

This feature appeared in the May/June 2012 issue of Australian Life Scientist. To subscribe to the magazine, go here.