C4X Discovery : collaboration with E-Therapeutics identifies new pathophysiological mechanisms in Parkinson’s disease

C4X Discovery Holdings plc

('C4XD' or the 'Company')

C4X Discovery collaboration with E-Therapeutics identifies new pathophysiological mechanisms in Parkinson's disease

Early results point to novel approaches to drug discovery for this debilitating disease

Manchester and Oxford, UK, 6 December 2018: C4X Discovery Holdings plc (C4X.L) ('C4XD') and e-therapeutics plc (AIM: ETX, 'e-therapeutics'), the network-driven drug discovery (NDD) company, are pleased to announce an update on their collaboration (announced 1st May 2018) to identify novel intervention strategies for the potential treatment of Parkinson's Disease (PD).

This collaboration has identified additional novel biological pathways for the treatment of PD and both companies consider that further work in this area has the potential to transform the treatment landscape for these patients, where there remains a significant unmet need.

Craig Fox, Chief Scientific Officer at C4XD, said: 'Following the identification of novel drug targets for the treatment of PD from the direct findings from our Taxonomy3® platform we recognise there still remains untapped potential in this proprietary analysis. By working with the team at e-therapeutics and utilising their NDD platform, we have been able to access cutting-edge mathematical and data analysis techniques to augment and interrogate the vast amount of biological information currently available in both public and private databases. This combination has identified additional novel biological pathways for the treatment of PD and we look forward to moving these findings forward to initiate new drug discovery programmes.'

Alan Whitmore, Head of Discovery Biology at e-therapeutics, said: 'The initial results from this collaboration highlight the critical importance of considering biology in a network context to gain insights into clinically relevant biological mechanisms in complex disease. The ability to link genetic data to disease mechanism remains one of the greatest challenges of our industry. By using the advanced computational analytics of our NDD platform, we have been able to confirm the centrality of a number of known mechanisms in PD and, importantly, identify potential new ones. This in turn, opens up the prospect of new approaches to the discovery of effective novel drugs to tackle this and other undertreated, debilitating conditions.'

Further details of the collaboration

PD is a progressive neurological disease which affects up to 10 million people worldwide and incidence is increasing as the global population ages¹. Whilst to date some PD drivers have been identified, this has not resulted in any novel therapies.

C4XD's proprietary genetic target discovery technology Taxonomy3® has found multiple novel disease-associated genes in Parkinson's Disease (PD) in addition to identifying discrete patient sub-groups that could potentially provide an opportunity in stratified medicine. It has been estimated that selecting genetically supported drug targets should double the success rate of investigational new drugs in clinical development². These genetic discoveries provide a significant opportunity to uncover biological processes central to the causation and progression of disease.

e-therapeutics proprietary Network-Driven Drug Discovery (NDD) approach has been applied to this unique and rich dataset. Using e-therapeutics' cutting-edge technology, harnessing the latest mathematical and data analysis techniques to augment and interrogate this complex biological information, the study analysed approximately 200 PD-associated genes identified by C4XD's Taxonomy3 genomics platform.

Initial results derived using the advanced computational analytics of the e-therapeutics NDD platform have identified novel potential pathophysiological mechanisms relevant to PD as well as highlighting known mechanisms. The implications of these insights are now being explored further and suggest a number of novel intervention strategies that could be taken forward using ETX's NDD approach as well as providing another basis on which to select targets derived directly from C4XD's Taxonomy3® platform. Ultimately this approach might yield new drugs to treat this debilitating disease.

Importantly, the combination of network aware approaches and genetic target discovery has identified novel relevant biological pathways and processes that when targeted may subsequently address the pathophysiological phenotype. Key to this is the ability of the network perspective to tie together complex genetic information. This leads us to believe that the synergistic power of NDD with direct genetic findings will lead to new disease insights and identification of better treatments for PD.

Both C4XD and e-therapeutics believe their Taxonomy3® and NDD platform approaches are particularly relevant to diseases with poorly or partially characterised genetic predispositions, including PD, Alzheimer's, and inflammatory disorders such as multiple sclerosis. Both companies consider that further work in this area has the potential to transform the treatment landscape for these disorders, where there remains a significant unmet need.

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¹Parkinson's News Today. (2018). Parkinson's Disease Statistics - Parkinson's News Today. [online] Available at: https://parkinsonsnewstoday.com/parkinsons-disease-statistics/ [Accessed 19 Nov. 2018].

²Nelson et al, The support of human genetic evidence for approved drug indications. Nature Genetics volume 47, pages 856-860 (2015)