Bionomics' oncology approach targets cancer stem cell therapies in solid tumours. Cancer Stem Cells are the seeds that give rise to initial tumour formation and if left unchecked, give rise to tumour recurrence and metastasis.

BNC101

BNC101 is a monoclonal antibody that targets cancer stem cells. Cancer stem cells are a subset of cells within a tumor thought to play a critical role in tumour initiation, recurrence and metastasis. They are also implicated in resistance to current standard of care cancer treatments. Eliminating cancer stem cells, in conjunction with other therapies that address the tumor bulk, represents a new cancer treatment paradigm that could offer a distinct advantage over existing strategies and a solution for chemoresistance.

BNC101 was originally developed at Biogen Idec, a global leader in biotechnology. Biogen Idec’s Cancer Stem Cells Program, started in 2004 and led for 7 years by Dr. Peter Chu and Dr. Chris Reyes, led to the discovery of BNC101, a unique and novel therapeutic highly specific for cancer stem cells. Through its acquisition of Eclipse Therapeutics, a Biogen Idec spinout founded in 2010 to advance BNC101 and other novel CSC therapeutics into the clinic, Bionomics acquired a promising CSC drug pipeline, Eclipse’s CSC Rx Discovery Platform, and deep expertise and intellectual property in CSC therapeutics. 

BNC101 is a first-in-class humanized monoclonal antibody that targets a cancer stem cell receptor highly overexpressed in most solid tumours, including colorectal, breast, pancreatic, ovarian, lung, liver and skin cancer. Preclinical studies performed at Biogen Idec and Eclipse Therapeutics showed BNC101 to be highly effective at targeting and reducing the frequency of cancer stem cells derived from primary patient colorectal tumours both in vitro and in vivo. Additional preclinical studies suggest that BNC101 may be relatively safe compared to competitor CSC agents currently being developed, as a result of its therapeutic window.

Bionomics plans to file an IND for BNC101 in 2015.

 

 

BNC105   

BNC105 is a novel compound being developed by Bionomics as a Vascular Disrupting Agent (VDA) for treatment of cancer. VDAs are drugs that disrupt the blood vessels that nourish tumours.

This approach has a number of advantages over classical chemotherapy: occlusion of a single blood vessel can result in the death of thousands of tumour cells, it is applicable to a wide variety of cancers and since the therapy targets the blood vessel rather than the tumour, it is unlikely that mutant tumour cells will emerge that are resistant to the therapy.

The company has employed its proprietary MultiCore® technology to create novel compounds that effectively shut down tumour blood vessels without affecting the blood vessels of normal organs.

Competitive Advantages of BNC105

BNC105 has several important properties that make it superior to VDAs being developed by other companies:

  • Safety and tolerability now established in a large patient group.
  • BNC105 has a higher therapeutic index, meaning that that there is a larger window between its effective dose and the dose at which toxic effects are observed (in mice the therapeutic index for BNC105 is 26 times greater than that for Combretastatin A4 (CA4), another VDA in development). It achieves this superior therapeutic index by being more selective for blood vessels of tumours than CA4.
  • BNC105 has a "dual mode" of operation. In addition to its effect as a VDA, BNC105 has a direct cytotoxic effect upon tumour cells. Bionomics has demonstrated in preclinical studies that these combined activities enable BNC105 to inhibit tumour growth as a single agent, an effect not seen with combretastatin.
  • It also effectively combines with radiation therapy and with other cytotoxic agents to generate a greater anti-tumour response.
  • Pharmacokinetic studies demonstrate that BNC105 is selectively retained within tumours. This "lock-in" effect improves the selectivity of its action upon the cancer, leading to an increased safety margin in treatment and may explain the lack of serious side-effects of BNC105 treatment in clinical trials to date.
  • BNC105 does not appear to be affected by the multidrug resistance gene, P-glycoprotein which affects the bioavailability of many anticancer agents by causing secretion of the drug out of cells.

A 47-centre Phase II clinical trial of BNC105 in combination with everolimus (marketed by Novartis as Afinitor) in patients with metastatic Renal Cell Carcinoma completed enrolment in June 2013.  In May 2012, Bionomics launched a Phase I trial of BNC105 in women with ovarian cancer in Australia, New Zealand and the United States.  The 18-centre randomised Phase I/II trial is evaluating BNC105 in combination with carboplatin and gemcitabine. 

Bionomics completed a Phase II trial of BNC 105 as a second line treatment for metastastic mesothelioma in 2012.