David Madge



Xention Ltd. is a drug discovery company that specializes in the discovery of orally available, small molecule, ion channel modulators. The company, which has over 50 employees, is located in Cambridge (UK). Over the last decade, Xention has accumulated extensive expertise and capabilities in the ion channel drug discovery area, which has led to its status as a global leader in its core disciplines; electrophysiology and ion channel medicinal chemistry. The key elements of Xention’s capabilities comprise:

  • Comprehensive manual and automated electrophysiology screening capabilities, which cover a wide range of throughput capacities.
  • A highly experienced medicinal chemistry team with ion channel-focussed experience and comprehensive discovery chemistry capabilities.
  • Extensive ion channel tissue culture experience and expertise, enabling the development of stable cell lines expressing single channels of interest in recombinant systems, and provision of suitable cells for automated electrophysiology screening.
  • Expertise in developing detailed translational assays through the use of electrophysiological recordings from relevant tissue types. For example, Xention routinely obtain human atrial tissue, which has allowed the development of an ex vivo proof-of-concept assay that enables the characterization of compounds on action potentials measured from disease relevant tissue.
  • An extensive compound screening collection, which includes a collection of around 70,000 compounds focused towards ion channels.
  • Detailed in silico ion channel databases and efficacy prediction capabilities based on large datasets from proprietary sources and literature data.

The decision to concentrate its discovery capabilities exclusively on target class, rather than on a particular disease focus, has allowed Xention to work on projects across a wide range of therapeutic areas, whilst continually building expertise and facilities that can be rapidly implemented for any ion channel target. This discovery platform has been leveraged to support both internal projects in the cardiovascular area, as well as enabling the provision of an integrated drug discovery service for companies that share an interest in ion channels as drug targets.

In the cardiovascular area, Xention has focused its resources on two targets, IKur and IKACh, which are widely recognised by cardiologists as the preferred targets for the prevention of atrial fibrillation. Xention’s lead drug candidate XEN-D0103, an IKur antagonist, has recently completed a Phase 1 clinical study, and is expected to progress into a Phase 2 clinical study later in 2012. XEN-D0103, which is highly selective to IKur over other atrial and non-atrial ion channels, was observed to be well tolerated with no significant adverse effects being reported. In addition, Xention has successfully identified highly potent and selective antagonists of IKACh, which have been observed to selectively prolong the human atrial action potential in ex vivo studies. A clinical development candidate is expected to be selected shortly.

Furthermore, Xention has signed two major research collaborations, with Ono Pharmaceutical Co. Ltd. and with the Grϋnenthal Group, which are focused on the identification of pre-clinical candidates for exciting ion channel targets in other therapeutic areas. This discovery service is an aspect of the business that Xention plan to expand by establishing further collaborative research alliances, which may build on existing internal programmes already in place at Xention or may involve new targets selected by our collaborators.

In addition to the major research alliances with Ono Pharmaceutical and Grϋnenthal, Xention has also forged collaborations with other pharma and academic research partners by participating in FP7 sponsored projects.

  • EDICT – a consortium focused on generating structural information on ion channels and transporters, as well as providing computational tools focused on ion channel targets.
  • Eurostars – Xention partnered with Axxam SpA to identify novel, orally bioavailable, small molecule inhibitors of the ICRAC current as new autoimmune therapies for the treatment of diseases, such as rheumatoid arthritis and multiple sclerosis.
  • MAREX – a consortium investigating the potential of new marine-sourced bioactive molecules as ion channel modulators.
  • EUTRAF – a consortium that undertook a five-year research project with the objective of improving the diagnosis, prevention and treatment of AF through the application of a highly integrative research approach.

The expanding number of collaborative projects at Xention has been paralleled by the identification and validation of further ion channel targets, as well as an increasing global awareness of the tractability and attractiveness of ion channels as a drug target class. This is reflected by the fact that the average number of ion channel publications retrieved by Pubmed, over five year periods, has increased progressively over the last 20 years. Xention plans to capitalize on the growing interest in ion channels by continuing to expand its discovery expertise and capabilities, with the intention of developing more research collaborations.



For more information please contact:

Dr David Madge
VP, Research
Xention Limited
Iconix Park
London Road
CB22 3EG

Tel: +44 1223 493938
Fax: +44 1223 493901
Email: david.madge@xention.com




Gabriele Costantino
Univ. of Parma, IT

Editorial Committee

Erden Banoglu
Gazi Univ., TR

Lucija Peterlin Masic
Univ. of Ljubljana, SLO

Leonardo Scapozza
Univ. of Geneve, CH

Wolfgang Sippl
Univ. Halle-Wittenberg, DE

Sarah Skerratt
Pfizer, Sandwich, UK

Executive Committee

Uli Stilz President
Gerhard F. Ecker Past Pres.
Koen Augustyns Secretary
Rasmus P. Clausen Treasurer
Hein Coolen Member
Gabriele Costantino Member
Phil Jones Member

For more information please contact info@efmc.info