Project: Dual System Independent Sequential Targeting
This project has four principal goals:_x000D_1) Identification of specific genomic DNA sequences associated with proven cancer targets _x000D_2) Preclinical development of an optimised lead therapeutic against a selected target_x000D_3) The Design of antibody-drug conjugates (ADC) targeted at specific tumour types in cancer, or other cell types indicated in other therapeutic areas._x000D_4) Preclinical development of an optimised ADC against specific cell type(s) or tumours. _x000D__x000D_Hence a two pronged attack:_x000D_a) At one level the design and optimisation of an antigene system to silence the aberrant genes, and the evaluation of desired and potential off target effects. In addition this system is directed at silencing the gene, and not trying to deal with the gene product. _x000D_b) Targeting of the tumour that has resulted from the aberrant gene (or is associated with the gene) and directing the ADC directly to the tumour resulting in a direct and rapid reduction in tumour size, with reduced drug concentration and fewer systemic or ‘off target’ effects, and/or specific cell types implicated in other disease areas, such as arthritis._x000D__x000D_A strong, diverse consortium has been assembled to meet these goals bringing expertise in the design and synthesis of antigene therapeutics and diagnostics. ValiRx PLC is a UK biotech company with a novel gene knockdown technology platform, GeneICE (Gene Inactivation through Chromatin Engineering) that works by selectively targeting specific sequences of DNA in aberrant (diseases associated) genes. The DNA is then collapsed by recruiting a natural gene regulatory enzyme so that it cannot be read and translated into RNA and subsequently proteins. This approach to gene inactivation at the DNA level, rather than at the RNA level (such as antisense and RNA interference approaches) is potentially highly efficacious and long lasting with high specificity. The company has a strong IP position and will have optimised aspects of the linking chemistry prior to commencement of this project. Critical aspects to this approach include identification of the target sequence, to avoid modifying non-disease associated genes, and design modifications to the triplex forming sequence to optimise binding to the target sequence. ValiRx has now identified its first set of oligonucleotides for this preclinical programme. Pharmatest Services, Finnish contract research organization, will lead the consortium and it will focus on the discovery of new therapeutic targets for the GeneICE technology. Global transcriptomics profiling of the functional effects of the targeted gene silencing will be performed to analyse the epigenetic regulation of gene expression as a result of the GeneICE activity and to probe for non-specific effects._x000D__x000D_The targeting antibodies will be based on antibody fragments (scFv) designed and produced by Dr. Ahuva Nissim of ‘Barts and the London’, Queen Mary’s School of Medicine and Dentistry (QMUL), an international expert in antibody technology and various forms of phage display. Human antibody fragments will be produced and conjugated with other biological molecules, or small molecules. _x000D__x000D_The primary market for Gene knockdown based therapeutics as well as tissue targeting will initially focus on the oncology sector. The business model will be to license/P clinical development beyond phase Ib, or enter into a co-development deal if a potential P wishes to P at the end of preclinical phase. This strategy is supported by the growing appetite for new technologies from large pharma to address dwindling product pipelines and imminent patent losses from blockbuster products. Michael Harris, Executive Editor of BioWorld magazine commented that the “imminent reality of gene therapy technologies and drugs” is seen as a key factor in turning bioPing activities between innovative biotech companies and large pharma into “a permanent drug development market core dynamic”. Development of a detailed preclinical data package will allow progression to first in man clinical studies, a major value inflection point, and a critical step towards attracting interest from large Pharma. _x000D__x000D_Several headline deals between big Pharma and companies with gene silencing technologies have taken place over the last few years. Both Roche and Takeda have announced development deals with Alnylam with potential values of $1Bn and Merck and Co. aquired Sirna for $1.1Bn in 2006. Validation of the technology in a specific disease model will open further opportunities for collaborative development in additional “non-core” disease states outside of the oncology field. ValiRx has in vitro data in several models including Alzheimer’s. Earlier opportunities exist for the development of knockdown reagents for use in the life science industry. Gene silencing is a valuable tool for studying effects of specific genes and proteins as well as drug target validation.
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Acronym
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D-SIST
(Reference Number: 8295)
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Duration
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01/09/2013 - 31/08/2016
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Project Topic
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The project will develop dual targeting system to combat cancer by developing GeneICE technology to enable the selective silencing of specific genes in cell lines and by design and validation of antibody-drug conjugates (ADC) targeted at specific tumour types in cancer.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 10
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Project partner
