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harminox Ltd, a cancer drug discovery and development company originally spun out from the UK’s Oxford University, has gained an exclusive worldwide licence to Cancer Research Technology’s (CRT) programme targeting telomeres and telomerase.

Telomeres are the repeat sequences of DNA and associated proteins found at the ends of chromosomes, acting as protective shields to maintain chromosomal integrity, explained CRT, the development and commercial arm of Cancer Research UK. Telomerase is the enzyme responsible for maintaining the telomeres.

In normal cells, noted CRT, the telomere shields get smaller every time a cell divides, eventually shrinking to the point where the cell stops dividing and eventually dies. In most cancer cells, though, that part of the telomere lost in cell division is restored by the telomerase enzyme, allowing the cells to continue dividing.

Telomerase is thought to be expressed in around 90% of tumours but its activity is barely detectable in normal tissues, making the enzyme an important target for cancer drug development, CRT said.

According to Professor Malcolm Stevens, who led the original research programme funded by Cancer Research UK at the University of Nottingham and is chief scientific officer at Nottingham-based Pharminox, the telomeres programme “has made considerable progress and we have already seen promising anti-tumour activity in preclinical tests”. But there is “still some way to go before the compounds from the programme could be used as new cancer treatments”, he cautioned.

The compounds discovered at the University of Nottingham appear to have a dual mechanism of action: they prevent telomerase from replacing the telomeric DNA lost in cell division and they also have the capacity to disrupt the protective cap around the telomere itself, inducing cell damage and exerting a more rapid anti-tumour effect, Professor Stevens pointed out.

Under the terms of the licensing agreement, CRT will receive an undisclosed upfront payment and will be eligible for milestone payments as well as royalties on net sales of any resulting treatments. The upfront payment, milestones and royalties will be shared between CRT, the University of Nottingham and The Institute of Cancer Research, whose scientists contributed to the research.

Last week the Nobel Prize in Physiology or Medicine for 2009 went to three US researchers – Elizabeth Blackburn, Carol Greider and Jack Szostak – for discovering how chromosomes are protected by telomeres and telomerase.

In December 2006, Pharminox signed a deal potentially worth up to US$40 million with US pharmaceutical major Schering-Plough for a joint research programme aimed at discovering novel small molecule anti-cancer therapies.

In April of that year, Pharminox signed an agreement with Cancer Research Technology giving the company a 12-month option to in-license exclusive worldwide development and commercialisation rights to a preclinical oncology programme based on Professor Stevens' research and focused on telomere signalling targeted agents (TSTAs).