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The programme has come out of research by Professor Malcolm Stevens OBE, Director of the Cancer Research UK Experimental Cancer Chemotherapy group at the University of Nottingham, who is also Chief Scientific Officer of Pharminox.
Under the terms of the agreement, CRT has granted Pharminox an exclusive 12-month option to in-license exclusive worldwide development and commercialisation rights to the programme. A lead candidate, RHPS4, has already been selected and is expected to move into formal preclinical development within the next 12 months.
Commenting on today’s announcement, Peter Worrall, Chief Executive of Pharminox, said: “This agreement is our third collaboration with CRT and we welcome the opportunity to build on the strong relationship that we already have with CRT. The TSTA programme is a very valuable addition to our portfolio and represents another important step towards our goal of building a pipeline of targeted, small-molecule anti-cancer agents with novel mechanisms of action spanning research through to early-stage clinical development.”
Mechanistic studies with RHPS4 suggest that it exerts its activity primarily by disrupting the function of the telomere, the single-stranded piece of DNA at the end of chromosomes. RHPS4 is also a potent inhibitor of telomerase, an enzyme whose role is to maintain telomere length in order to prevent cells entering a process known as apoptosis (programmed cell death). Telomerase is known to be highly up-regulated in 90% of all cancer cells.
RHPS4 has shown potent anti-tumour activity against a range of common human tumours in in vitro and in vivo testing. In xenograft models, it has shown tumour growth inhibition of up to 90% relative to control when given as a single agent. In a combination study with the marketed anti-cancer agent paclitaxel (Taxoltm) in a uterine tumour model, it produced complete and rapid eradication of the tumours with no observable re-growth throughout the remainder of the study. Paclitaxel given as a single agent in a separate arm of the same study achieved good tumour growth inhibition but no tumour regression.
Professor Stevens commented: “I am delighted that Pharminox has been able to secure the rights to this exciting programme. TSTAs represent a highly promising new area of cancer research and we believe RHPS4 to be one of the most advanced compounds in this class. During the option period our intention is to carry out additional in vivo studies to build on the impressive data that we have already seen and to inform the design of a clinical trial.”
Dr Phil L’Huillier, CRT’s Director of Business Management, added, “We are enthusiastic about the prospects for this novel programme and we are pleased to be able to facilitate its continued development under the auspices of Pharminox and Professor Stevens.”
Notes to editors
About telomere signalling targeted agents
Telomeres are the single stranded pieces of DNA that protect the ends of chromosomes. In normal cells, a fragment of the telomere is lost each time the cell divides until a critical telomere length is reached, triggering a process of senescence (cell ageing) followed by apoptosis (programmed cell death).
Approximately 90% of cancer cells produce an enzyme called telomerase, unlike the majority of normal cells, which essentially produce no telomerase. The role of this enzyme is to replace the fragments of the telomere lost in cell division, stabilising telomere length above the critical threshold required for cell survival. In this way cancer cells are able to circumvent the normal cell ageing process and become “immortalised”, leading to the uncontrolled cell proliferation that is a feature of cancer tumours.
Research in this area previously focused on compounds that inhibit telomerase, but it is now believed that such compounds may not be sufficiently fast acting to have therapeutic utility. Compounds such as RHPS4 that have a direct effect on the function of the telomere are predicted to produce a much more rapid onset of action.
About Pharminox Ltd
Pharminox (www.pharminox.com) is an emerging UK biopharmaceutical company focused on the discovery and development of small molecule drugs for the treatment of cancer. It was formed in late 2001 as a spin-out from Oxford University with backing from IP2IPO plc, but has subsequently moved its discovery research activities to Nottingham. It owns or has acquired the rights to a number of novel programmes from the laboratories of Professor Malcolm Stevens OBE, Director of the Cancer Research UK Experimental Cancer Chemotherapy Group, and is currently seeking further funding to progress these programmes into development.
Professor Stevens, who joined Pharminox in 2004 as Chief Scientific Officer, has had a long and distinguished career in cancer research. He was responsible for the discovery and early development of temozolomide (Temodaltm), a treatment for glioma (the most prevalent form of brain cancer), which is marketed by Schering Plough and in 2005 achieved global sales of almost $600 million.
