Opening up opportunities in autoimmune disease treatment
Cambridge, UK, 5th November 2012.
Domainex Ltd., a UK-based drug discovery company, has developed a number of chemical series with potent and selective activity against two closely-related kinases TBK1 and IKKepsilon. IL-17 mediated signaling is known to induce the expression of cytokines and other effectors that can cause a variety of immunological diseases such as psoriasis and Chronic Obstructive Pulmonary Disease (COPD). Domainex researchers are now the first to report that small-molecule inhibitors of TBK1/IKKepsilon are able to affect IL-17 signaling. These results suggest that the Domainex inhibitors may have utility in a wide range of clinically-important diseases that have great unmet medical needs.
Recent clinical studies reported in The New England Journal of Medicine by Lilly and Amgen have shown that neutralizing anti-IL-17 monoclonal antibodies can have a major impact on psoriasis (Leonardi et al. 2012 and Papp et al. 2012 respectively). The demonstration by Domainex that small-molecule drugs targeting IKKepsilon can inhibit IL-17 signaling indicates that these compounds have great clinical potential in this disease and other important settings.
Domainex has developed three series of drug-like compounds, each series having inhibitors with high potency and selectivity against other kinases. The lead compounds have good metabolic properties and the Company is now driving these compounds forwards towards a clinical candidate.
Domainex’s Research Director, Trevor Perrior, said: “Domainex, in collaboration with The Institute of Cancer Research, has previously shown that its inhibitors of TBK1/IKKepsilon have activity against a variety of cancer cell-lines. Domainex has also demonstrated that its inhibitors are very potent blockers of interferon-beta production in immune cells, showing the compounds may have utility in diseases such as lupus. The latest finding that our TBK1/IKKepsilon inhibitors can also inhibit IL-17 signaling suggests that the compounds are also of potential use for treatment of other major diseases such as psoriasis and COPD. Domainex has recently obtained funding from the government-backed Biomedical Catalyst programme to explore the use of its inhibitors of IKKepsilon in COPD.”
Eddy Littler, CEO of Domainex, said: “The latest results showing the activity of Domainex’s TBK1/IKKepsilon inhibitors against IL-17 signaling reinforces the fact that this project is of very high interest to pharma. Indeed Domainex is already in discussion with a number of potential partners with a view to them helping us to progress the programme to the clinic, and fully exploit its enormous potential. We are also grateful for the Biomedical Catalyst award that will enable us to extend our work to COPD, and help us fully exploit our intellectual property on inhibitors of TBK1 and IKKepsilon”.
- Domainex uses unique and proprietary technologies to resolve common bottlenecks facing the pharmaceutical and biotechnology industries in the post-genomic era. Major discovery 'gaps' exist between the vast amount of genomic information that is now available, the accessibility of the corresponding proteins for use in target validation and drug discovery, and the identification of robust hits in a cost effective manner. Founded in 2002, Domainex is a privately owned company based in Cambridge, UK.
- Domainex has developed a discovery platform, which enables rapid progression of drug discovery projects from novel target through to Candidate Drug by means of its Combinatorial Domain Hunting technology, LeadBuilder virtual hit screening software, and its integrated approach to medicinal and computational chemistry.
- Domainex is developing an oncology-focused pipeline of novel drug compounds. It has chosen a number of well-validated but challenging targets, that we have successfully unlocked with its Combinatorial Domain Hunting and LeadBuilder technologies. The pipeline is focused upon some exciting kinases and on lysine methyltransferases (KMTs) involved in epigenetics. Domainex intends to take these projects into lead optimization and candidate selection, and looks for collaborators who may be interested in working with Domainex on their further development through the clinic.
- Domainex’s patented CDH technology enables the cloning and expression of soluble drug target protein domains in E. coli, followed by the identification of those constructs that are able to bind a ligand. This enables binding assays to be developed, facilitating hit identification studies. In only 3-4 months, all expressible ligand binding domains of a target protein are identified (from libraries of 20,000-100,000 constructs), enabling key rate limiting steps in early drug discovery to be easily overcome and resulting in large time savings over standard approaches.
- Domainex has also developed LeadBuilder - a virtual screening approach for targets which is specifically aimed at quickly identifying hit molecules that are ideally suited for further development.
- The experienced medicinal chemistry team has a proven track record in supporting biotech or university groups by providing expertise to take hit compounds through lead optimization and on to candidate selection. Three compounds to date arising from these collaborations are currently in clinical evaluation, with two additional drugs in preclinical studies.
- The Biomedical Catalyst, announced by Prime Minister David Cameron in December 2011, is a programme of public funding designed to deliver growth to the UK life sciences sector. Delivered jointly by the Medical Research Council and the Technology Strategy Board, the Biomedical Catalyst provides responsive and effective support for the best life science opportunities arising in the UK. The programme is open to UK academics and SMEs and seeks to support those opportunities which demonstrate the highest scientific and commercial potential, irrespective of medical area. For further information please visit: http://www.innovateuk.org/content/competition/biomedical-catalyst.ashx
For more information see: www.domainex.co.uk or contact:
Head of Business Development
Tel +44 (0)7775 437107