Public Funding for Cellcentric Limited

1 in 4 cancer deaths in men and women are a result of lung cancer. Despite significant advances in recent years, both in terms of early detection and novel therapies, there remains a significant unmet need for cost-effective drugs that offer long term benefits. CellCentric has developed a novel, highly potent potential drug for the aggressive form of prostate cancer, that is expected to be taken orally 1-2 times a day. This is advancing to clinical trials. Recent studies reported in the literature by others (Jan-Mar 2016) have unexpectedly, indicated that CellCentric's drug could have specific application for 10-15% of patients who have non-small cell and small cell lung cancers. These tumours are readily identifiable with existing bioassays. The patients, particularly in the advanced stages, have few alternatives. This project will use tests involving cells and human tumour tissues to seek to extend some of the findings reported by others, and confirm whether CellCentric's easy to administer drug could be used beyond prostate cancer, for lung cancer too. Even a 10-15% lung cancer opportunity represents a significant patient population, that would derive meaningful clinical benefit from such an approach.

Prostate cancer is the second leading cause of mortality among men. Initial treatments focus on reducing the levels of circulating male hormones in the body which the cancer requires for growth. Overtime however, in 10-20% of cases, the cancer cells circumvent this treatment and develop into ‘castration-resistant’ prostate cancer (CRPC). This is the lethal form of the disease. CellCentric have identified an enzyme that regulates the cellular processes that lead to the development of this lethal form of the disease. It is proposed to identify and optimise an inhibitor of this enzyme as a potential new drug for the treatment of CRPC. On-going research at CellCentric has identified prototype inhibitors of the enzyme. The research proposal aims to optimise these inhibitors so that they can be assessed for anti-tumour activity in models of CRPC. If these ‘proof of concept’ studies are successful, a candidate compound will be nominated for further evaluation in human clinical trials.

The aim is to develop a process which can distinguish good from bad induced pluripotent stem cells (iPS cells) in terms of their differentiation capacity. Batches of iPS cells derived from multiple patient tissue samples will be analysed and grouped in terms of their ability to differentiate into the three cell lineages (endoderm, mesoderm and ectoderm). The key epigenetic marks which are the most important as distinguishing features to be able to divide them into “good” (those which can fully differentiate) versus “bad” (those which can’t) cell lines will be determined. Thus, the output of the project will be an optimised and validated key signature gene set predictive of the iPS cells differentiation capacity which would form the basis of a diagnostic tool

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