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.

On August 30, 2001 Antisoma plc, the UK-based biopharmaceutical company developing novel targeted cancer therapies, reported that it has in-licensed DMXAA, a vascular targeting agent, from Cancer Research Ventures Limited ("CRV"), a global cancer technology transfer company created by the Cancer Research Campaign ("CRC") (Press release, Cancer Research Technology, AUG 30, 2001, View Source [SID1234523474]). The product, which has already completed two Phase I studies, brings the number of products Antisoma has in clinical development to four.

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Vascular targeting agents have significant potential to selectively restrict the blood flow to a tumour that would otherwise feed its growth. Additionally, DMXAA appears to cause the blood vessels to release substances such as tumour necrosis factor and interferons which may make the tumour more sensitive to other chemotherapeutic agents.

DMXAA was discovered by Professors Bruce Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre ("ACSRC"), University of Auckland, New Zealand. In extensive pre-clinical studies carried out by the ACSRC, DMXAA, when used in combination with a number of other anti-cancer agents, particularly taxanes, was seen to control the growth of tumours in animal models and, in several cases, to eradicate them.

"It is still at an early stage, and we have a long way to go before we know what human tumours it may be most effective in, but the results so far have been very promising," Professor Baguley said. "A single dose of DMXAA in combination with another chemotherapeutic agent caused tumours to disappear at a rate we have not seen before."

Dose-ranging, Phase I clinical trials, sponsored by the CRC in the UK and in New Zealand, have provided safety data and indicate that DMXAA causes a reduction in tumour blood flow when used alone.

Glyn Edwards, Antisoma’s Chief Executive Officer, commented:
"This fascinating approach to tumour control further broadens our clinical pipeline. DMXAA has tremendous potential to treat established solid tumours, which comprise a major proportion of all diagnosed cancer. As a small molecule it further diversifies our portfolio. We hope to complete Phase I testing of DMXAA alone and start Phase Ib studies using DMXAA in combination with chemotherapy by the end of 2002."

CRV’s Chief Executive Officer, Dr. Guy Wood-Gush, added: "This deal is an excellent example of how CRV works with partners on a global basis. We have brought together a commercially experienced partner, Antisoma, and an important new drug discovered by scientists in New Zealand, supported by data from Phase I clinical trials run by the CRC. This clearly illustrates CRV’s key role in the worldwide market for early stage cancer products and CRV’s strong growth prospects."

Antisoma acquired exclusive worldwide rights to DMXAA in exchange for an upfront consideration of £700,000 inclusive of an equity component, as well as future milestones and royalties.

On June 5, 2001 Cancer Research Ventures ("CRV") reported that it had signed a license with Epigenomics which focuses on developing diagnostics and therapeutics based on the study of DNA methylation patterns of the genome (Press release, Cancer Research Technology, JUN 5, 2001, View Source [SID1234523475]). They have extensive expertise, proprietary intellectual property and know how in this field.

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Dr Guldberg funded by the Danish Cancer Society has invented a useful, patent protected high speed methylation detection assay. It is hoped that it will lead the way to the use on a routine basis of diagnostic tests based on DNA methylation.

Epigenomics will develop and commercialise this novel methylation detection assay. Most recent research has shown that DNA methylation patterns correlate with various disease states and in particular with cancer. Identification of the aberrantly methylated genes will certainly lead to the development of novel diagnostics and therapeutics.

CRV provides commercialisation and intellectual property management services to cancer research institutes world-wide. CRV’s goal is to bridge the gap between exciting new research, in this case funded by the DCS at the Institute of Cancer Biology and its timely development by the best suited commercial partner.