Monday 25 July 2005
PARP Inhibitor Targeted at Inherited Breast and Ovarian Cancers
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
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Notes to editors
- PARP inhibitors
- Research has shown that women who inherit faults in either the BRCA1 or BRCA2 genes, where the tumour cells have lost a specific mechanism that repairs damaged DNA are predisposed to a higher incidence of breast and ovarian tumours. PARP inhibitors work by selectively killing cells where this form of DNA repair is absent and so are highly effective in killing BRCA deficient tumour cells and other similar tumour cells. Normal cells are largely unaffected by the drug as they still possess this crucial DNA repair mechanism. Other tumour types that lack or display dysfunction of BRCA 1&2 or other components of homologous recombination DNA repair (“BRCAness”) may also respond similarly to use of a PARP inhibitor.
- KuDOS Pharmaceuticals Limited holds a leading position in the discovery and development of drugs based upon the science of DNA damage sensing, signalling and repair to address unmet medical needs in cancer treatment. The company develops small molecule drugs that selectively inhibit the repair process in cancer cells thus facilitating their destruction and improving cancer management.
- KuDOS currently has three drugs in clinical trials: Patrin™, which is being developed for the treatment of cancers resistant to alkylating agents, AQ4N, which targets hypoxic regions of tumours, and PARP inhibitors which target tumours cells lacking the BRCA1 and BRCA2 genes. Research continues on DNA-PK, ATM and mTOR inhibitors.
- For more information about KuDOS please visit, www.kudospharma.co.uk.
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