ELF programmes available for partnering

News
16 April 2020

Since its inception, the European Lead Factory (ELF) has been recruiting high quality drug discovery programmes from all over Europe. Over the past five years, the thorough recruitment and selection process has led to a balanced portfolio of innovative disease targets that have been screened against our unique compound library. We now have three successful ELF programmes in the field of CNS & Neurology available for partnering.

The first programme is an in vivo Proof of Concept, targeting an ion channel with the potential to generate a new class of analgesic drugs, with the opportunity to treat chronic pain without affecting normal sensation and perception. This project has identified a number of highly potent and selective ion channel enhancers using a combination of fluorescent Tl+ flux screening and electrophysiology assays. Kinetic analysis of these data sets has allowed for triaging of compounds by modality of action, selecting for the most pharmacological advantageous profiles. Exemplar compounds from the lead series have been further profiled, exploring their pharmacokinetic and ADME properties both in vitro and in vivo. By partnering, the project team hopes to further develop their in vivo testing for efficacy in pain conditions and continue toxicology and ADME testing.

The second programme has been developed by Graeme Wilkinson’s team at The Research Network Ltd. In collaboration with the European Lead Factory, they have identified and further exemplified novel lead-like compounds that are potent, sub-nM inhibitors of the MrgD receptor. In addition, they have generated pharmacokinetic data, which supports their oral bioavailability. Their goal is to build on this work and identify candidate molecules that have the potential for clinical development in pain and / or itch (pruritus). This will be done through a focused lead optimisation campaign that will include the demonstration of efficacy and target engagement.

Thirdly, we have a programme developed in Italy that is applicable for a range of human diseases, with highly variable phenotypes, affecting the skeletal system (e.g. brachyolmia type 3 & spondyloepiphyseal dysplasia), and the peripheral nervous system (e.g. Charcot-Marie-Tooth disease type 2). The scope of the project is the development of selective TRPV4 antagonists. After HTS on a recombinant human TRPV4 cell-based assay, 50 molecules showing pIC50 > 5 on TRPV4 and pIC50 < 4.7 on mock cells were prioritised. Some Hits appear to possess interesting levels of potency, with a pIC50 > 7. The team is looking for a partner with complementary expertise and capabilities in medicinal chemistry, in vitro ADME, in vivo PK, and animal models to further develop the molecules through the subsequent phases of drug discovery.

These three programmes are now available for partnering. If you are interested in collaborating and progressing programmes like these, please get in touch with the Programme Office at programme@europeanleadfactory.eu. And make sure to keep an eye on our Portfolio page, as we’ll be updating it regularly with new programmes.