A number of ORIL compounds were tested in a series of in vitro cell growth inhibition (IC50) studies. The compounds were tested against a panel of over 40 cell lines representing a wide range of cancer indications including breast, lung, colon, ovary, prostate, melanoma and pancreas. The inhibition profiles for our lead candidate, ORIL007, in a subset of these cell lines are shown in Figure 1.
Figure 1. ORIL007 has been shown to have a very distinctive inhibition profile with a dramatic drop in survival for all of the cancer cells tested.
Importantly, in addition to these highly positive results in vitro, ORIL007 has also been proven to be effective against tumours in vivo. Formulated ORIL007 was administered to mice that had been inoculated with MIA PaCa-2 pancreatic cancer cells. The response, compared with vehicle, is shown in Figure 2.
Figure 2. This study used intravenous and then intraperitoneal administration of liposomal ORIL007. It clearly illustrates the effectiveness of administration of ORIL007.
For a development drug, showing in vitro and in vivo efficacy is a minimum requirement. One of the most common stumbling blocks in drug development is finding that the candidate drug is not only effective against the target tumour but also toxic to the patient. Toxicology analysis, such as MTD (maximum tolerated dose) studies performed in vivo can shed light on a drug’s toxicological profile. An MTD study was conducted using intravenous administration of ORIL-007 in mice. The results, showing that ORIL007 is safe to be administered in vivo, are shown in Figure 3.
Figure 3. No weight loss was found in an MTD study with a prototype formulation.
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