Portfolio

Seeding the priority medicines of the future

From the start, the European Lead Factory has been recruiting high quality 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.

New programmes available for partnering

Previously highlighted programmes

The crowdsourced portfolio currently contains >80 drug discovery programmes distributed among all relevant therapeutic areas. As this portfolio matures, the results are starting to be disseminated to the wider public. The first follow-up investments have been publicly announced, patents have been granted to Programme Owners and collaborations are initiated to further progress the results. The success of the ELF approach has been widely acknowledged and the output has shown to be of high quality, worth following up and investment-ready. Funding for further development has been secured for several programmes, and by March 2018 two programmes have led to partnering deals being closed between the Programme Owner and an established pharmaceutical company.

The EU Lead Factory has selected target programmes continuously over the past years with the start in 2013. As a consequence, only a handful of programmes have progressed to the stage where results can be disclosed. The major impact of the portfolio and opportunities for investment and translating the ELF results towards the clinic are to be expected in the upcoming years.

New programmes available for partnering

We have three successful ELF programmes in the field of CNS & Neurology 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.

Programmes available for partnering

  1. Pain | In vivo PoC | New class of analgesic drugs
  2. CNS & Neurology | Lead optimization | MrgD receptor inhibitor
  3. CNS & Neurology | Lead optimization | TRPV4 antagonist
  4. Neglected Tropical Diseases | Early Hit | REL1
  5. CNS & Neurology | Early Hit | Adrenomedullinreceptor antagonist

Previously highlighted programmes

  1. Metabolic diseases / cardiovascular | Lead optimization | Selective agonists for EPAC1
  2. Oncology | Lead optimization | KLK6 reduction
  3. CNS & Neurology | On the way to clinical candidate selection | KEAP1 inhibitors to combat neurodegenerative diseases
  4. Metabolic diseases | Preclinical development | New target for metabolic diseases
  5. Oncology | On the way to clinical candidate selection | Selective inhibitors of ACSS2
  6. CNS & Neurology | Lead optimization | CNS-active NAPE-PLD inhibitor
  7. Antimicrobial resistance| Lead to candidate | Novel antibiotics
  8. Neglected tropical diseases | Lead optimization | New chemotherapeutic options for Leishmaniasis
  9. Neglected tropical diseases |Lead optimization | Selective inhibitors over human PDEs
  10. Oncology | Discontinued | IDO1 inhibitors
  11. Oncology | Discontinued | Kinase inhibitor for Acute Myeloid Leukemia

Programmes available for partnering

Pain | In vivo PoC | New class of analgesic drugs

This 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.

CNS & Neurology | Lead optimization | MrgD receptor inhibitor

This 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.

CNS & Neurology | Lead optimization | TRPV4 antagonist

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.

Neglected Tropical Diseases | Early Hit | REL1

Trypanosomatid parasites cause a variety of devastating neglected diseases in humans and their livestock, including leishmaniasis, Chagas disease and animal African trypanosomiasis. A characteristic property of these organisms is a remarkably complex mitochondrial RNA editing process that, as a key player, involves an enzyme called RNA editing ligase 1 (REL1). An ELF programme has targeted REL1 and delivered chemically diverse small molecule inhibitors, some of which inhibit REL1 from several trypanosomatid species. The Programme Owner’s laboratory has expertise in molecular parasitology, biophysical characterisation of protein-ligand interactions and protein crystallography and has access to animal models of disease. They are now looking for partners with complementary expertise in medicinal chemistry and ADME/PK to further develop the molecules through the subsequent phases of drug discovery.

CNS & Neurology | Early Hit | Adrenomedullinreceptor antagonist

Adrenomedullinreceptor (AM) antagonists as potential therapeutic targets for major depressive disorder. This program has identified non—peptidic AM receptor modulators. These compounds could be a crucial first step towards the elucidation the biological function/activity of these receptors, with a view to develop novel therapies for the treatment conditions such as MDD, anxiety disorders and chronic pain.

AM is a 52 amino acid peptide that has partial structural homology with the calcitonin gene-related peptide (CGRP) and has shown anti-inflammatory activities and has previously been linked with several psychiatric disorders, as well as chronic pain. AM has been proposed to have several functions in the CNS including neurogenesis. AM works through a complex of three proteins including the G protein-coupled receptor related to the calcitonin receptor, CALCRL, and the CGRP-receptor component protein, RCP. CALCRL and RCP associate with two different receptor activity-modifying proteins (RAMPs) generating two different AM receptors (CALCRL+RAMP2 = AM1 and CALCRL+RAMP3 = AM2), which are essential for functional activity.


Previously highlighted programmes

Metabolic diseases / cardiovascular | Lead optimization | Selective agonists for EPAC1

Scientists from the Yarwood Lab and the European Screening Centre have jointly published on the discovery of a new class of EPAC activators. The study, which describes the identification, optimisation and characterisation of a new chemical class of selective agonists for EPAC1, is the result of another successful collaboration within the framework of the European Lead Factory (ELF).

Read more.

Oncology | Lead optimization | KLK6 reduction

Scientists from the German Cancer Research Center (DKFZ) have successfully discovered potent and selective inhibitors of enzymes associated with the development of some cancers and neurodegenerative diseases. Published in ChemMedChem, the findings mark a significant step in the development of potential new cancer treatments.

Read more.

CNS & Neurology | On the way to clinical candidate selection | KEAP1 inhibitors to combat neurodegenerative diseases

Keapstone Therapeutics is preparing to make the next steps in clinical candidate selection and first-in-human studies. This investment brings the total seed investment to € 2,4 million. Last year Parkinson’s UK together with Sheffield University launched the virtual biotech Keapstone Therapeutics to further develop compounds that boost the internal cellular defence mechanisms against oxidative stress to combat neurogenerative diseases.

Read more.

Metabolic diseases | Preclinical development | New target for metabolic diseases

Servier, an independent international pharmaceutical company, and Scandicure, a Swedish spin-out of the University of Gothenburg, today announced the establishment of an agreement to exploit Scandicure’s innovation in the field of metabolic disease. Scandicure, in collaboration with the IMI-funded European Lead Factory, has developed inhibitors of a novel biological target for non-alcoholic steatohepatitis (NASH), type-2 diabetes and potentially other metabolic diseases.

Read more.

Oncology | On the way to clinical candidate selection | Selective inhibitors of ACSS2

Metabomed, an Israeli biotech company that has been successful in progressing results through the European Lead Factory (ELF), has discovered a series of potent and selective inhibitors of ACSS2 (the AcetylCoA Short chain Synthase 2 enzyme) for the treatment of cancers dependent on acetate metabolism. Metabomed’s recent successes have led to the company securing a further $12.5 million in funding. These funds will go towards moving the clinical candidate for its ACSS2 programme towards IND approval.

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CNS & Neurology | Lead optimization | CNS-active NAPE-PLD inhibitor

In his screening proposal to ELF, Professor van der Stelt suggested to search for new inhibitors of NAPE-PLD, the protein responsible for the production of anandamide in the brain. The ELF partners carried out High-Throughput Screening (HTS) on the JECL and performed deselection assays ending up with five high-quality hits with four different chemotypes. Further optimisation of the hits by the Leiden chemists and their collaborators led to the discovery and characterisation of LEI-401 as the first CNS-active NAPE-PLD inhibitor. The findings presented by the team may open up new avenues for the treatment of anxiety disorders like post-traumatic stress.

Read more.

Antimicrobial resistance| Lead to candidate | Novel antibiotics

The University of Oxford takes the next step in targeting antimicrobial resistance, with help of the results and hit compounds delivered by the European Lead Factory. The Oxford team, led by Professor Chris Schofield, has got the opportunity to collaborate with the European Gram-Negative Antibacterial Engine (ENABLE) project to further progress this programme towards clinical development.

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Neglected tropical diseases | Lead optimization | New chemotherapeutic options for Leishmaniasis

Leishmania parasites cause leishmaniasis, a neglected tropical disease found in parts of tropics, subtropics and Southern Europe. The infection is transmitted through the bite of infected phlebotomine sand flies. Among the several forms of leishmaniasis, visceral leishmaniasis is the most severe form of the disease, which is fatal when left untreated. At the moment, there is no approved human vaccine and disease control relies mostly on chemotherapy, which is frequently linked to safety issues, drug resistance, among other issues, hindering disease eradication in endemic areas. Coming up with new chemotherapeutic options is, therefore, of utmost importance.

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Neglected tropical diseases |Lead optimization | Selective inhibitors over human PDEs

With help of the European Lead Factory, the Phosphodiesterase Inhibitors for Neglected Parasitic Diseases (PDE4NPD) project takes the next step towards developing novel drugs against kinetoplastid parasites such as Trypanosoma brucei, the causative parasite of African sleeping sickness, and Trypanosoma cruzi, causing Chagas disease.

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Oncology | Discontinued | IDO1 inhibitors

The Netherlands Translational Research Center (NTRC) has identified IDO1 inhibitors with best-in-class properties. They have been developed from a series of inhibitor compounds first identified by screening the JECL of the European Lead Factory against IOD1 and TDO, important targets in cancer immunotherapy. IDO1 and TDO are two structurally unrelated proteins that both catalyse the degradation of the amino acid tryptophan and regulate the T cell response. Thus, inhibition of IDO1 or TDO restore the body’s immune response against cancer cells. IDO1 and TDO inhibitors may also increase the efficacy of immunotherapy with immune checkpoint inhibitors.

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Oncology | Discontinued | Kinase inhibitor for Acute Myeloid Leukemia

Complementing the current anti-leukaemia arsenal with an inhibitor of this protein would have an impact in terms of survival, but also specifically in relapse prevention by suppressing leukemic residual disease. This target is a kinase with a pivotal role in the cytoskeleton dynamics. The cytoskeleton is involved in the cell division and proliferation of cancer. Screening this target against the compounds in the Joint European Compound Library during the Qualified Hit List (QHL) phase lead to finding chemical matter that was clearly different from what they had found before.

Read more.