On November 18, 2002 Cancer Research Technology Limited ("CRT") and the University of Cambridge (UK) reported a collaboration with Cyclacel Limited and a top 5 Pharmaceutical company to develop tools for target validation and drug discovery based on the technique of RNA interference (Press release, Cancer Research Technology, NOV 18, 2002, View Source [SID1234523466]).

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The term RNA interference ("RNAi") describes the cellular response to double-stranded RNA that results in sequence-driven gene specific silencing. Originally established as an important tool for functional genomics in the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, the potential for this technology was recently recognised in higher eukaryotes. In late 1999, Dr. Magdalena Zernicka-Goetz and colleagues (Dr. Florence Wianny, Professors David Glover and Martin Evans) at the University of Cambridge (UK) provided the first definitive demonstration of RNAi-mediated inhibition of endogenous genes in mammalian cells. This work in oocytes and early stage embryos sparked a flurry of research in the area, culminating recently in the use of short interfering double stranded RNA (siRNA) to achieve knockdown of a wide range of mammalian genes, and the development of specific vectors to express these effectors.

There are a number of published patents on techniques for performing RNAi, and undoubtedly more applications in the pipeline. CRT is the holder of two key patent applications in the field, one of which relates to the work of Dr. Zernicka-Goetz and colleagues. The second patent filing from CRT covers pSUPER, a vector for long-term expression of RNAi effectors in mammalian cells, developed at the Netherlands Cancer Institute (Amsterdam) in the group of Professor Rene Bernards. CRT is offering licenses to this portfolio of intellectual property, branded the SUPER RNAiTM System, for target validation, drug discovery and therapeutics. Several pharmaceutical and biotechnology companies are working with CRT towards generating RNAi-based systems to meet the current demands of the industry for higher throughput analysis of mammalian gene function and rapid production of disease models to aid drug discovery. In addition, CRT is exploring the potential for a new class of therapeutics, using RNAi for the inhibition of genes that are aberrantly expressed in cancers.

The collaboration announced today is funded in part by Cancer Research UK. The partners aim to build on the pioneering work in the Cambridge laboratory, and the recent exciting discoveries in the field, to establish RNAi as a viable tool for transient or persistent gene knockdown in mammalian cells and whole animals (e.g. the mouse). The successful development and optimisation of RNAi in mammalian systems will facilitate gene analysis in the academic laboratory, meanwhile use of this technology for commercial target validation and drug development will accelerate the gene-to-drug process.

On October 2, 2002 Cancer Research UK reported its new technology transfer company with a remit to exploit the fruits of its world class research programme into preventative strategies, diagnostic kits and new therapies for the benefit of cancer patients (Press release, Cancer Research Technology, OCT 2, 2002, View Source [SID1234523468]).

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Cancer Research Technology (CRT) is formed through the merger of Cancer Research Ventures (CRV) and Imperial Cancer Research Technology (ICRT), the respective technology transfer companies of the Cancer Research Campaign and the Imperial Cancer Research Fund who themselves merged on February 4, 2002, to become Cancer Research UK.

Harpal Kumar has been appointed as Chief Executive. David Newbigging, Deputy Chairman of the Council of Cancer Research UK, has been appointed non-executive Chairman and it is intended that Melanie Lee, who is a non-executive Director of CRT and Research and Development Director of Celltech plc, will succeed him in due course

On August 19, 2002 De Novo Pharmaceuticals Ltd, The Northern Institute for Cancer Research at the University of Newcastle and Cancer Research Ventures Ltd are pleased to reported that they have entered into a collaborative agreement for the discovery of small molecule inhibitors of the MDM2-p53 interaction (Press release, Cancer Research Technology, AUG 19, 2002, View Source [SID1234523469]). The MDM2-p53 pathway is a target which is implicated in the suppression of abnormal cell proliferation, and therefore may have therapeutic potential in several forms of cancer.

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Under the terms of the collaboration, full details of which have not been disclosed, De Novo Pharmaceuticals will provide drug discovery expertise through their suite of proprietary software to develop small molecule inhibitors based on seed molecules provided by The Northern Institute for Cancer Research. The Northern Institute for Cancer Research and Cancer Research Ventures have considerable expertise in this research area and will provide medicinal chemistry and screening for the output of the collaboration.

Dr Ian Hardcastle of The Northern Institute for Cancer Research commented, "We are delighted to have the opportunity to work with De Novo Pharmaceuticals in our quest for novel small molecule drug candidates against this important protein target. We believe this collaboration with De Novo will enable the Northern Institute for Cancer Research and Cancer Research Ventures to accelerate research against this important therapeutic target".

Dr Steven Beasley, Chief Operating Officer of De Novo, added, "Our discovery portfolio concentrates on key target areas where there is an urgent need for high quality leads with potential for rapid progression into development. As we move forwards, we are building a network of efficient and flexible collaborations with academic groups and Universities where this adds value to the Company. We are delighted to be working with The Northern Institute for Cancer Research and Cancer Research Ventures Ltd, who have done much of the pioneering work on this important target.”

"CRV are delighted to be able to facilitate this collaboration which highlights the quality of Cancer Research UK-funded science at The University of Newcastle, a leading institution in the fight against cancer" said Dr Guy Wood-Gush, CRV Chief Executive.

On July 1, 2002 Cancer Research Ventures ("CRV") reported that it had signed a non-exclusive license with Exelixis, Inc, USA for the rights to two patent families relating to the use of certain transposon-based technologies, which can be used to transfer DNA across the species barrier (Press release, Cancer Research Technology, JUL 1, 2002, View Source [SID1234523471]). The technology was jointly developed by the Netherlands Cancer Institute, Amsterdam and Crucell, bv, Leiden (formerly IntroGene).

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CRV was pivotal in mediating a mutually acceptable revenue sharing agreement between the two inventing parties and assigned in the intellectual property to act as the exploitation partner on their behalf. CRV ensures that all revenues received from licensing the invention are returned to both parties in a proportion reflecting their contribution to the invention.

Simon Youlton, the project manager responsible for this technology at CRV said that he "was expecting this to be the first non-exclusive license to a technology that will have considerable utility to any company wishing to validate gene targets in various different animal models. It may also prove to be a very versatile system for the construction of gene delivery vehicles for research and possibly gene therapy".

CRV’s CEO, Dr. Guy Wood-Gush added that "this validates the international role CRV plays in facilitating the transfer of key technologies for the benefit of future developments in the pharmaceutical industry whilst ensuring the inventors and their respective institutions are adequately rewarded for their efforts".

On April 8, 2002 Cancer Research Ventures (‘CRV’) reported that it has signed an agreement with BioSphings AG to assign rights to a patent estate that it had formerly been appointed to commercialise (Press release, Cancer Research Technology, APR 8, 2002, View Source [SID1234523470]). CRV has invested in many exciting early stage cancer developments, over recent years and this was the second advance CRV has taken forward on behalf of the inventor Dr. Eberhard Amtmann from The German Cancer Centre (‘DKFZ’) in Heidelberg. The new company, BioSphings of which Dr.Amtmann is a co-founder, will take the development of this exciting inhibitor of neutral sphingomyelinase in to the clinic, alongside its other clinical candidate, which is a Herpes Simplex Anti-viral cream.

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Dr Amtmann’s earlier research at DKFZ had selected the lead compound from a large anti-viral screen and subsequently found that the drug was highly selective for a particular form of sphingomyelinases that were up-regulated in tissue and cells showing pathogenic phenotype but not to the same extent in normal tissues. Neutral Sphingomyelinase is a critical enzyme involved in the Fas/CD95 driven apoptotic pathway, and it is thought that the abundance of the enzyme in these diseased cells prevents the cells from undergoing apoptosis or ‘programmed cell death’ to completion. For example in arthritis, inflammation is caused by a build up of activated T-cells. In a normal immune response the activated T-cells will die naturally once they have completed their task. Dr Amtmann has shown that an inhibitor of neutral sphingomyelinase will restore the apoptotic pathway and allow cells to die. Unlike other potential and current therapies for auto-immune disorders this does not rely on a non-specific suppression of the immune system which can prove dangerous for the patient. Instead it is highly selective only for the cells that the body has already targeted for apoptosis after induction of Fas. Consequently the inhibitor has no effect on non-activated T-cells or other cells of the immune system such as the antibody producing B-cells. The inhibitor has shown very clear anti neoplastic properties in mouse xenografts where it sensitises tumours to the effects of cisplatin and Tumour Necrosis Factor and when administered orally, has been shown to remove T-cell lymphomas in mice.

CRV has to date underwritten the patent costs and ensured a good intellectual property position in the field over the last two years. Now that the inventor has secured finance for the clinical development, CRV were very happy to hand back rights to this promising candidate. This continues the recent trend CRV has shown to help foster new start-up companies, mainly in the cancer field, with Qugen, Singapore and Chroma, Oxford, UK being the most recent. CRV said that it has plans to incorporate another UK based company in the next two months based on cancer pro-drugs and is currently involved in helping seed companies in the Netherlands and Italy.