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.

On March 27, 2002 RiboTargets Limited, the structure-based pharmaceutical research company, Cancer Research Ventures Limited ("CRV"), a global cancer technology transfer company, and The Institute of Cancer Research reported a collaboration to identify and develop inhibitors of the HSP90 ‘chaperone’ family as potential anti-cancer drugs (Press release, Cancer Research Technology, MAR 27, 2002, View Source [SID1234523472]).

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Proteins called "oncogenic proteins" are responsible for uncontrolled cell division – a characteristic of tumour growth in cancer. Chaperone proteins, such as HSP90, are of particular interest in anti-cancer drug development because they ensure these oncogenic proteins remain in the correct shape to function. The Institute of Cancer Research has extensive experience working on chaperone proteins and has identified some compounds which inhibit HSP90’s activity using their in-house assays. Professor Paul Workman and Professor Laurence Pearl have led the research in this area at The Institute of Cancer Research. Funding for this work has come from Cancer Research UK, The Institute of Cancer Research and The Wellcome Trust.

Under the terms of the collaboration, The Institute of Cancer Research will continue to evaluate the inhibitors of HSP90 and continue to provide the expertise in the biology of HSP90 and the pre-clinical and clinical trials necessary for drug development. RiboTargets will provide chemistry and structure-based design capability to identify new inhibitors and, going forward, the Company will manage the emerging intellectual property and take responsibility for development and commercialisation of any products that arise from the collaboration. Significant resources will be employed at both RiboTargets and The Institute of Cancer Research as part of this collaboration. Financial details have not been disclosed.

Commenting on the collaboration, Dr Susan Bright, Director of the Enterprise Unit at The Institute of Cancer Research, said: "For over five years, The Institute of Cancer Research has been researching the role of HSP90 proteins in cancer and we will be using our capability to translate this research into a drug discovery programme. RiboTargets has developed a powerful drug identification technology and will provide the development and commercial expertise to translate our scientific work into new agents that will inhibit the growth of tumours. We look forward to using our expertise alongside RiboTargets."

Guy Wood-Gush, Chief Executive of CRV, added: "This deal demonstrates CRV’s central role in the commercialisation of new innovative cancer therapies. Through its close association with Cancer Research UK, the Institute of Cancer Research, and other leading research institutions around the world, CRV is able to facilitate the development of many novel cancer related technologies, so bringing benefit to cancer patients."

Simon Sturge, Chief Executive of RiboTargets, commented: "This collaboration marks RiboTargets’ entry into the oncology arena and we are delighted to be working with two of the world’s leading cancer research organisations. In particular, The Institute of Cancer Research and Cancer Research UK have the experience in conducting clinical trials with novel anti-cancer therapies which will be invaluable to the collaboration. We also believe that this collaboration validates the general applicability of our technology and highlights the role that structure-based design can play in the identification and development of new drugs."

On November 1, 2001 Cancer Research Ventures (CRV) Limited, Auckland UniServices Limited and The Institute of Cancer Research, London, reported that they had formed a new company to develop new therapeutic strategies for the treatment of cancer (Press release, Cancer Research Technology, NOV 1, 2001, View Source [SID1234523473]). Proacta Therapeutics Limited, which is to be based in Auckland, New Zealand, has been formed to further develop novel prodrugs and the technology for their localised activation only at the site of tumours.

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Proacta has a strong and broad Intellectual Property portfolio, holding 21 patent families based on technology from the Institute of Cancer Research and the Auckland Cancer Society Research Centre (ACSRC) of the University of Auckland.

The Company’s focus is to develop new treatment modalities for cancer, which are directly targeted at the tumour itself. The approach Proacta is taking is to develop essentially non-toxic prodrugs which do not have the often severe and unpleasant side effects associated with conventional chemotherapy and radiotherapy. The prodrugs are converted to highly active anti-cancer agents under certain conditions that either occur naturally within tumours, or are artificially generated locally within the tumour.

Proacta’s prodrug activation strategies include a number of proprietary enzymes delivered to the tumour by gene therapy, and the natural hypoxia found in most solid tumours. Proacta also has access to a new class of prodrugs which are activated by direct radiation of the tumour itself and which may, by substantially increasing the efficiency of existing radiotherapy treatment, allow lower doses of radiation to be given. In addition to its prodrug strategies, Proacta has a number of directly cytotoxic compounds, which can be targeted to the tumour using selective antibodies.

The Company’s scientists include Professor Caroline Springer and Dr. Richard Marais of The Institute of Cancer Research, based in the Cancer Research Campaign Centre for Cancer Therapeutics, and Professor Bill Denny and Bill Wilson of the ACSRC.

"The establishment of Proacta is a very encouraging development which should accelerate the development of this very exciting new cancer treatment modality", said Dr. Guy Wood-Gush, CEO of CRV in London. "The establishment of such a notable scientific team drawn from these top cancer research centres in the UK and New Zealand clearly underpins the exciting potential of these technologies."

"We have been collaborating with the Auckland team of scientists for some time and we are very much looking forward to implementing our plans and taking our drug candidates into the commercial arena", said Professor Springer of The Institute of Cancer Research.

Last week it was announced in Seattle that Proacta and Seattle Genetics Inc. had entered into a licensing agreement with Seattle Genetics acquiring from Proacta licensed-rights to a class of cell-killing Compounds. President and Chief Scientific Officer of Seattle Genetics, Dr. Clay B. Siegall, said the drugs developed by Proacta’s scientists would add significantly to his company’s pipeline of novel agents under development for the treatment of cancer.

"The Proacta compounds represent a unique class of drugs that are ideally suited for targeted drug delivery, providing a means to selectively kill cancer cells while limiting damage to normal tissue", he said.

Proacta plans to develop a certain number of its company proprietary prodrug candidates jointly with other parties as well as through an in-house drug development programme.

Shareholders in Proacta include CRV, The Institute of Cancer Research, Auckland UniServices Limited and the Centre for Applied Microbiological Research (CAMR) based in Porton Down, UK.