Prolarix™ for primary liver cancer and other selected tumours
Prolarix™ fact sheet
We are developing Prolarix™, a novel targeted cancer therapy based on an elegant prodrug system involving the co-administration of two small molecules. This approach exploits the finding that an endogenous enzyme called NQO2 is over-produced in a number of cancers, including hepatic cell carcinoma (HCC), relative to normal human tissues.
We have discovered a way of enabling NQO2 (using a co-factor called caricotamide; previously designated EP-0152R which is a vitamin analogue) to convert an inactive prodrug called tretazicar (previously CB1954) to a potent cancer killing agent. The treatment is expected to be associated with less toxicity than is the case with many drugs used to treat cancer because NQO2 is more abundant in certain tumour cells than in normal tissue, and systemic exposure to the activated drug is expected to be limited by its short half-life. The system has been demonstrated to be effective in both in vitro and in vivo model systems.
A phase 1 study of Prolarix™ is being run under the auspices of Cancer Research UK (CRUK). The maximum tolerated dose (MTD) for Prolarix™ has been determined, and an additional cohort of six patients is being recruited to evaluate the effects of repeated cycles of Prolarix™ on various tumour types. The study is expected to complete in the first half of 2008. Having reached the MTD, Protherics plans to start a phase 2 programme in the first half of 2008 to investigate tumour responses in primary liver cancer (HCC) patients treated with up to six cycles of Prolarix™. This phase 2 programme will comprise an open-label run-in to a larger controlled study in which Prolarix™ will be added to sorafenib and compared with sorafenib alone. The open-label run-in should provide an early indication of potential efficacy in HCC patients.
HCC is the fourth most common cause of cancer in the world and is commonly linked to chronic hepatitis B & C infection, alcoholism and exposure to aflatoxin. Neither chemotherapy nor radiotherapy is effective in this cancer and surgery or transplantation is only possible in a small number of cases. As a result, the outcome for patients is poor with less than 20% surviving beyond 1 year, and less than 5% surviving beyond 5 years. Despite the considerable unmet clinical need, there are few new therapies under development for the treatment of HCC.
A patent protecting our technology in regard to the co-factor has been granted in the UK, US, Hong Kong and is under examination in other territories.
We intend to develop Prolarix™ in the US and EU in the lead indication of HCC, and to sign a licensing partner for Asia. Please contact our
Business Development team for more information on the Prolarix™ licensing opportunity.