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IOmet Pharma Demonstrates Superior In Vivo PK/PD Properties in Pre-Clinical IDO, TDO and Dual IDO/TDO Cancer Immunotherapy ProgramsIOmet Pharma, a privately-held company focused on cancer immunotherapy and cancer metabolism, today presented data demonstrating superior pharmacokinetic / pharmacodynamic (PK/PD) properties in its pre-clinical IDO, TDO and IDO/TDO Dual Inhibitor programs. The data was presented at the Keystone Tumor Immunology Symposium in Banff, Alberta, Canada. IOmet is developing multiple, distinct novel chemical series of potent, IDO-selective, TDO-selective and dual-acting IDO/TDO inhibitors. IDO (indoleamine-2,3-dioxygenase) and TDO (tryptophan-2,3-dioxygenase), the rate-limiting enzymes in the pathway that metabolises the essential amino acid tryptophan, have emerged as key targets for the pharmaceutical industry in the cancer immunotherapy field. Overexpression of these enzymes has been detected in a variety of cancers, including glioma, melanoma, lung, ovarian and colorectal cancers, and is associated with poor prognosis and survival. IDO and TDO overexpression leads to tryptophan depletion and high tumour levels of the breakdown product, kynurenine. This elevated kynurenine/tryptophan (K/T) ratio supresses the body's immune response to cancer, thus facilitating tumour progression and metastass. Extensive preclinical evidence, and emerging clinical data, suggests that inhibition of IDO and/or TDO may synergise with, and help overcome resistance to, existing clinical cancer therapies, in particular other immunotherapy-based treatments Compared to IDO inhibitors identified to date, IOmet's compounds demonstrated highly favourable in vitro human and rodent PK properties, which translated to superior in vivo PK/PD relationships. In a poster presentation today, IOmet Pharma showed that, as expected, all three classes of inhibitor raised tryptophan and lowered kynurenine levels, thereby reducing the plasma K/T ratio by up to 80%, following a single 10 mg/kg oral dose in rats. Sustained lowering of the K/T ratio was observed up to 8-12 hours post dosing. Cancer immunotherapy is an exciting and rapidly growing field of research investigating the use of therapies that harness the body's own immune system in the fight against cancer. Tumours utilise a variety of mechanisms to evade host immune detection. The aim of the cancer immunotherapy approach is to prevent a tumour's ability to suppress its own detection and elimination by the patient's immune system. About Iomet Pharma IOmet Pharma Ltd is a privately-held drug discovery company based in Edinburgh, UK. Founded in 2008, IOmet is focused on the development of innovative medicines for the treatment of cancer, with particular emphasis on the fields of cancer immunotherapy and cancer metabolism. IOmet has a team with a proven track record of success in bringing small molecules from discovery phase to the clinic, and is advised by internationally-renowned experts in the fields of cancer immunotherapy (Prof Holbrook Kohrt, Stanford Cancer Institute) and oncology drug development (Dr Rob Williams, Chief Drug Development Scientist, Cancer Research UK (CRUK) and Dr Ian Waddell, Head of Biology, Drug Discovery Unit, CRUK Manchester Institute). For more information, please visit www.iometpharma.com |
