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Public Funding for C4X Discovery Limited

Registration Number 06324250

University of Manchester (The) and C4X Discovery Limited

2019-05-01 to 2022-06-30
Knowledge Transfer Partnership
To transfer, and embed into drug discovery, cutting edge biomolecular NMR techniques for the characterisation of dynamics of protein: ligand complexes in solution. Synergies will be identified and developed with the proprietary ligand NMR technology.

Harnessing the synergy between Conformetrix technology and crystallography to expedite identification of novel, selective a4b7 integrin inhibitors for the treatment of IBD

139,965
2018-11-01 to 2019-09-30
Feasibility Studies
"The objective for this project is to deliver an oral, small molecule anti-inflammatory agent for the treatment of mild-severe, inflammatory bowel disease (IBD). IBD is a collection of idiopathic diseases caused by a dysregulated immune response to host intestinal microflora. The most common sub-types are ulcerative colitis (a continuous band of inflammation throughout the colon) and Crohn's disease (transmural, ""skip lesions"" affecting any segment of the gastrointestinal tract). IBD patients are stratified as mild, moderate or severe. The current standard treatment for mild patients is aminosalicylate progressing to corticosteroids and then immunosuppressants as disease severity increases. Treatment for mild-moderate patients sees mixed response and is associated with significant side-effects. Moderate/severe patients that do not respond to immunosuppressants are progressed on to biological therapies which have revolutionised the treatment of moderate/severe disease. Unfortunately, a significant proportion of patients do not respond to biological therapies often due to the production of neutralising antibodies. Gastroenterologists have identified a clear need to develop non-biological agents that effectively maintain remission in moderate/severe patients. This need also extends to mild-moderate patients where cost effective, oral, non-biological, anti-inflammatory treatments with improved efficacy and side effects could prevent disease progression. C4X Discovery will use its proprietary Conformetrix technology which has been previously been used to rapidly identify novel chemical scaffolds from known ligands, by elucidating their 3D shape(s) in solution. The technology will be used synergistically with protein crystallography to compare free and bound ligand 3D-shapes to pin-point the exact areas of the molecules that will need optimising leading to the identification of potent anti-inflammatory compounds. An effective, safe, oral small molecule therapy for IBD could meet the healthcare need across IBD patient severities and help reduce the significant economic burden caused by the disease. There are currently over 300,000 patients in the UK with IBD and prevalence increasing. The NHS economic cost of IBD was £720 million in 2006\. An effective oral anti-inflammatory agent will lower the healthcare burden by reduced hospitalisation of patients, lower Cost of Goods compared to biologics, and no necessity for hospital visits for administration, thereby increasing patient access to a life-changing therapy. The positive impact at a patient and community level would be a pain free, convenient, discreet medication reducing social stigma."

Oral Agonists of GPR142, an Innovative New Target for the Treatment of Type 2 Diabetes

139,640
2017-01-01 to 2017-12-31
Feasibility Studies
Type-2 diabetes (T2D) affects over 420 million people worldwide, creating an enormous healthcare and socio-economic burden. The GPR142 receptor has been recently reported to be an exciting new target for the treatment of T2D with several advantages. Firstly, its activation results in insulin secretion but only in the presence of high blood sugar levels, avoiding the life-threatening side effect of low blood sugar associated with insulin-based therapies. Secondly, GPR142-based medicines would be orally administered, avoiding compliance issues caused by injectable therapies. Additionally, activating GPR142 leads to the release of GLP-1 - a clinically validated mechanism for the treatment of T2D. By applying its proprietary NMR-based approach to drug discovery, C4X Discovery has identified hit molecules for GPR142. This project is scoped to characterise and develop these hits to enable a chemical optimisation programme aiming to ultimately lead to a new, convenient, safe and effective class of T2D medicine that would have an enormous positive impact on long-term patient health and reduce the economic burden associated with the disease.

C4X Discovery - Validation of GPR142 as a Target for Type II Diabetes

59,954
2015-04-01 to 2015-12-31
GRD Proof of Concept
Type-2 diabetes (T2D) affects over 340 million people worldwide, creating an enormous healthcare and socio-economic burden. The GPR142 receptor has been recently suggested as a potential new target for treating T2D with a key advantage: its activation results in insulin secretion as desired but, unlike other targets, it does this only in the presence of high blood sugar levels. Medicines that work through GPR142 should therefore provide marked health benefits over existing T2D therapies, as they will avoid the life-threatening side effect of low blood sugar levels. Moreover, GPR142-based medicines would be orally administered, avoiding the problems caused by injection-based therapies. Poor patient complaince with injectables results in many of the T2D disease symptoms and most of the healthcare and financial burden on the NHS. GPR142-based medicines, if feasible, would therefore not only substantially improve T2D sufferers’ health but also reduce the cost burden on the NHS too. This project aims to carry out vital studies to confirm if GPR142 is indeed the exciting new target for T2D that it promises to be. Very encouraging preliminary literature reports show beneficial effects in clinically relevant acute animal models but, because T2D is a chronic disease, further validation work to assess the chronic effects of GPR142 control is vital to see if it is suitable for safe, long term control. The aim of this project is to perform chronic target validation studies and, if positive, thereby open up a new and better class of T2D medications. If positive, C4X has a head-start in leading this new area, having already designed hit molecules for GPR142 with excellent properties. Positive results would justify a subsequent C4X drug development programme. In time, this would lead to the creation of a new, convenient, safe and effective class of T2D medicines that would have an enormous positive impact on long-term patient health and the economic burden associated with T2D.

Small-molecule agonists of GLP-1R for the treatment of Type-2 diabetes

148,293
2014-07-01 to 2015-09-30
Feasibility Studies
Type-2 diabetes has assumed almost epidemic proportions, resulting in a significant financial burden to healthcare systems in developed countries. GLP-1R agonism represents one of the mainstays of therapy for type-2 diabetes, but existing GLP-1 mimetics necessitate injection and have been associated with severe side effects. Through the use of its proprietary NMR-based approach to drug design, C4X Discovery (C4X) has built the first comprehensive pharmacophore GLP-1R agonist 'map' and used this to derive the smallest orthosteric agonist of GLP-1R so far reported. As part of the project, C4X will explore whether this molecule can form the basis of a chemical optimisation programme that will enable the creation of orally-available and cheaper alternatives to exisiting therapies, thereby providing a significant healthcare benefit in terms of increased patient convenience, improved compliance and reduced economic burden.

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