Cambridge, UK, 25 July 2005: KuDOS Pharmaceuticals Limited, the drug development company that targets DNA damage sensing and signalling to improve the treatment of cancer, today announced that the first patient has been dosed in a Phase I clinical study of its oral PARP inhibitor (polyADP ribose polymerase inhibitor).
Dr Peter Harris, Development Director of KuDOS commented, "The entry of our PARP inhibitor into the clinic represents a key milestone for KuDOS. This is the first time that this new oral anticancer agent has been administered to patients. KuDOS commenced its PARP discovery programme in 2000 and this represents the first product of its in-house research to enter the clinic."
Most patients are treated with drugs that kill tumour cells but also damage normal cells, leading to distressing side effects such as nausea and hair loss. The advantage of KuDOS' oral PARP inhibitor is that it is targeted at inherited breast and ovarian tumours (BRCA 1 and 2 deficient) and at a wider range of other cancers that display similar characteristics ("BRCAness"); tumour cells are killed while normal cells appear unaffected.
The Phase I study is being conducted at the Royal Marsden Hospital, Sutton, Surrey under the supervision of Professor Stanley Kaye and Dr Johann De Bono. The study will investigate the safety and tolerability of the PARP inhibitor in patients with solid tumours and provide key data to establish the human dose, using a new technique to measure the inhibition of the enzyme drug target. Patients with confirmed BRCA deficient tumours will also be eligible for enrolment in the study.
Prof. Stanley Kaye remarked "We are delighted to be conducting the first patient clinical study with this new agent especially as Professor Alan Ashworth, working in the Breakthrough Breast Cancer Centre at The Institute of Cancer Research, this hospital's academic partner, has been involved with KuDOS in ground breaking research to elucidate utility in BRCA1&2 deficient tumours."
Dr De Bono added "An orally active agent should make administration much more convenient for patients. This study will establish the safe and efficacious dose that can be taken forward into Phase II clinical studies in BRCA and other patients".
This clinical study follows the earlier publication in Nature of the underlying science where PARP inhibitors were shown to be selectively cytotoxic to tumours lacking BRCA 1 and 2; these include the inherited breast and ovarian cancers. Evidence is also accumulating that many more types of cancer displaying loss of BRCA or related components of the homologous recombination pathway may respond similarly to PARP inhibition. In addition, PARP inhibitors have been shown to enhance significantly the effect of a number of widely used cytotoxics that damage DNA. This enhancement should offer greater effectiveness of treatment of cancers with minimal increase in toxicities.