BNC105
BNC105 is a novel compound being developed by Bionomics as a Vascular Targeting Agent (VDA) for treatment of cancer. VDAs are drugs that disrupt the blood vessels which 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 MultiCoreŽ 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:
- 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 enhanced 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 tumor cells. Bionomics has demonstrated in preclinical studies that these combined activities enable BNC105 to inhibit tumor 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 an enhanced anti-tumour response.
- Pharmacokinetic studies demonstrate that BNC105 is selectively retained within tumors. This "lock-in" effect enhances the selectivity of its action upon the cancer, leading to an enhanced 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.
- BNC105 is now shown to be effective in animal models of six human tumour classes: head and neck, brain, prostate, breast, colon and lung.
In January 2008, Bionomics initiated Phase 1 human clinical studies of BNC105 under a US FDA IND. In June 2009, the Hoosier Oncology Group Inc, headquartered in Indianapolis, IN (USA) was engaged to undertake a Phase II clinical trial to evaluate the efficacy of BNC105 in renal cell carcinoma.
In December 2009, the Australasian Lung Cancer Trials Croup (ALTG) and the NHMRC Clinical Trials Centre (CTC) were contracted to conduct a Phase II clinical trial on 60 mesothelioma patients.
