Experience of others
“I work as a drug discovery manager at Parkinson’s UK, where I identify appropriate projects to fund and support. I see the frustrations of people with Parkinson’s in that they don’t have medicines to help them in a meaningful way. My driver is to be able to do good science, with a tangible outcome for these patients.
One of the projects we fund is spin-out company Keapstone Therapeutics. Dr Richard Mead (University of Sheffield) and his team aim to deliver potential new treatments for Parkinson’s. Their compounds and associated data package, which was developed together with the European Lead Factory, were particularly attractive to us. In order for our projects to be attractive for further development by big pharma companies, we work to industrial standards. These standards are much more stringent than academic ones, because pharma companies need confidence that a project will eventually reach fruition. ELF plays an important role in this. Firstly because the European Lead Factory educates academics in why industry-quality data is required and secondly because ELF helps them to produce these data.
The hit compounds in Richard Mead’s data package were validated to a degree you would expect to see in industry. This gave us confidence to fund the project for an initial 16-month period with a budget of 1.3 M GPB (1.5M€). Based on the positive results so far, it is likely that we will continue funding this project beyond the first term.
When potential collaborators do not yet have the appropriate starting points, ELF would definitely be an organisation we would direct them to. It is a proven opportunity and asset, with many examples of how it has been successful.”
“Selvita is a biotech company engaged in the discovery and development of breakthrough therapies in oncology. In one of our drug discovery programmes, we had performed internally a high troughput screening (HTS) of a 50k compound library, which resulted in only very few hits. As we truly believed in the target, we submitted the programme to the European Lead Factory. It gave us the great opportunity of screening a much larger drug discovery compound collection as well as having the subsequent validation cascade performed at ELF. The resulting Qualified Hit List was of high quality and the obtained chemical matter allowed us to initiate further chemical development at Selvita. One of the indirect benefits of the collaboration with the European Lead Factory was the opportunity to implement some of the ELF’s workflows, procedures and quality criteria to our internal research programmes.
Personally, I consider the European Lead Factory to be a great initiative. It can perfectly support SMEs, which often have the capabilities and the knowhow to progress the hits, but may lack the libraries and infrastructure for the extensive HTS to be run in-house. ELF has the experience, facilities, resources, actually all the assets, needed to successfully support drug discovery programmes. I truly hope that ELF will continue its operations, as I strongly believe it can be a real game changer for many drug discovery programmes.”
August, 2018
“We are working on inhibitors for glioma progression that are suitable as leads for drug development. The European Lead Factory provided us with a unique opportunity. There is absolutely no way a scientist at a university, not even at a top university, can run a high throughput screening on 500,000 compounds, each of which is drug-like. Many of the libraries that exist in academia are of little relevance in true drug discovery.
In addition, ELF has the best trained team imaginable for a small-molecule drug project, with the expertise to retrieve the right compounds from this extraordinary library. We were very impressed with the collaborative way of working with all the people involved in the process. They even suggested what experiments to run and they executed those with excellent quality. This is essential. It’s not only about having a good library. If you have all the money in the world but you don’t know how to make the cake, there will be no cake. In this case we got the best bakers in the world.
It will probably take 10 to 20 years before the true power and the effect of the European Lead Factory will be revealed. We already know that we have a fair chance of ending up with leads that can be developed into a drug. We wouldn’t have been able to reach the point where we’re at now without the European Lead Factory.”
March 2018
“Our goal at CELLIPSE is to develop new drugs for leukaemia patients. We applied to the European Lead Factory (ELF) program to identify new molecules that can be used as a starting point to develop a kinase inhibitor drug. The ability to have access to drug like compounds which come from big pharma is a major advantage. There are many chemical libraries available but many are not very drug like, in contrast to the compounds in the Joint European Compound Library. Also, the number of compounds you can screen against is extraordinary. We were quite impressed with the results obtained during our collaboration with ELF.
Another key asset for us is the access to expertise of the people working at ELF and the interaction with them, especially in the hit exploration phase. Getting from our Qualified Hit List to an optimised hit and later to a lead, requires having shared goals and objectives. The ELF scientists were clearly focused on one thing: the success of our program. Together, we achieved a lot.
For a small biotech company like ours, it is difficult to find a back-up compound. Most probably we wouldn’t have been able to generate back-up with an entirely different chemotype without ELF. For the credibility, validation and value of our drug discovery program this is very important. We will continue to work on the optimised hits we’ve obtained during the Improved Hit List phase, and we hope to start with animal studies soon. We would definitely recommend the European Lead Factory to other SMEs or French researchers.”
March 2018
"Based on my experience, I would say without hesitation that it is worthwhile to work with the European Lead Factory. The Research Network is a virtual entity, we don’t have physical labs. In order to generate new molecules, we need to have a drug discovery engine. That is where ELF comes in. We’ve been working with ELF for 3 years now, and in that time we’ve had five programs accepted. Two of these are about to exit the process and go into discussion with the pharma partners. If ELF didn’t exist, we wouldn’t be able to generate the chemical lead matter that is needed to develop and take forward a new project proposal.
The entire process witness of quality and the resulting compounds have proved suitable for in vivo testing. The value that EU Lead Factory can bring to generating potential new drug starting points and molecules which can be used to understand the mechanisms of human disease is vital."
December 2017
"For a relatively new research group such as ours, the European Lead Factory represents a fantastic opportunity to see the molecules prepared in our synthetic projects make a genuine impact in medicinal chemistry. Our group is interested in developing novel ring expansion approached to medium-sized ring and macrocyclic peptide mimetics.
However, at present we have neither the expertise nor the resources to run bioassays of our synthetic products. By working with the European Lead Factory, >50 of our compounds are now part of the Joint European Compound Library and will soon be part of the ELF screening set. The whole process was remarkably straightforward; after submitting our initial proposal and preparing 2 grams of a single synthetic intermediate, all the subsequent chemistry was done in an ELF partner laboratory.
It really couldn’t have been any easier from our perspective. To know that our products may one day contribute to addressing some of society's major health problems like cancer or antimicrobial resistance, is extremely satisfying and exciting!"
October 2017
"In 2018, an 18 trillion-dollar-bill will be paid to treat dementia and Alzheimer’s disease worldwide. It is a condition that will concern us all, either as a patient, as a relative or as one of the few and relatively lucky ones who will only have to pay that bill.
About 20 years ago, the Director of Research of my department, Prof Frank Gunn-Moore, discovered a protein, which he suspected was involved in the deterioration of the brain that causes dementia. In order to further investigate the potential for this protein as a drug target, we needed compounds to perturbate its action. My task was to develop an assay suitable for screening.
Thanks to the local funding from the Scottish Universities Life Science Alliance (SULSA), I could spend three–four weeks at the European Lead Factory Screening Centre in Newhouse. There, I could work in an industry-like setting to upgrade my assay to the ELF standard. Combining my knowledge of the protein with the ELF expertise and robotics enabled us to optimise the assay really quickly. For a postdoc like me, it was truly a unique experience. I’d recommend to anyone in academia to go for it and take advantage of the opportunity!"
October 2017
“High-throughput screening still is one of the main starting points for drug discovery. The EU Lead Factory provides academics and small pharmaceutical companies with access to a state-of-the-art platform for the identification of hit compounds. To have this facility at hand represents a fantastic breakthrough. In addition, the Joint European Compound Library (JECL) compares favourably with what I have seen from other screening collections. As an external advisor to one of the pharma partners, I get to evaluate their screening results to compose a Qualified Hit List of up to 50 compounds.
I have noticed that the JECL hit compounds are very ‘drug-like’: they are small with favourable physicochemical properties and limited unwanted functionality. Indeed, I have recommended the EU Lead Factory to academics interested in high-throughput screening against their drug target. Academics might not have the tools to develop a 384-well assay in-house, but it’s worth the effort to seek help elsewhere or to contact the Programme Office for advice: the EU Lead Factory is a unique resource with the potential to provide enormous value to small pharmaceutical companies and universities.”
September 2017
"Thanks to outcomes of our European Lead Factory programme, Parkinson’s UK decided to allocate 1 million GBP in a unique collaboration resulting in a joint-venture biotech company - Keapstone Therapeutics. The EU Lead Factory compounds inhibit a protein–protein interaction in a very interesting disease-related pathway triggering the internal cellular defence mechanisms against oxidative stress, which plays an important role in neurogenerative diseases like Parkinson’s disease and amyotrophic lateral sclerosis (ALS).
It would have been absolutely impossible without the high-quality work that the European Lead Factory provided. From assisting with protein production, the optimisation of the HTS assay, developing a totally new biophysical assay, the hit expansion and medicinal chemistry, new protein constructs, and finally also solving inhibitor-bound protein crystal structures. We made incredible breakthroughs! We see that the European Lead Factory is unique in many aspects. It gives us the opportunity to screen a very good and diverse set of compounds from different sources, including the big pharmaceutical companies’ proprietary collections.
Combined with cutting-edge resources, we have world-class infrastructure at our disposal. With this approach the European Lead Factory plays an important role in filling the gap between basic research and late stage drug discovery. The complex agreement might seem cumbersome, but in the end, it protects the target owner. This is a real plus. I truly recommend the European Lead Factory to all my colleagues.”
March 2017
“At our lab we are studying gut-derived pathogens. We have identified proteins involved in pathogen virulence that could be targeted in the combat against antibiotic resistance. To further advance our project, we needed chemical tools. This is why we applied to the European Lead Factory, which makes it possible to access a large and high-quality compound collection.
The infrastructure, expertise and experience of the EU Lead Factory is impressive. In fact, the list of assay requirements for the EU Lead Factory programmes have become the guideline for screen development by the members of the German Centre for Infection Research (DZIF). If they are fulfilled, we know that the assay and target is suitable for a larger screening campaign. We could not quite attain the threshold for one requirement, but that was resolved by one of my PhD students visiting the European Screening Centre site using their instruments.
Furthermore, the University of Oxford group have assisted us producing enough of our target protein to enable a high-throughput screening campaign. In parallel, we’re developing several secondary assays to prove true engagement of the hit compounds with the bacterial target in-house and in collaboration with other EU Lead Factory scientists. Eventually, we hope to use the resulting EU Lead Factory compounds in our mouse model and establish pharmaceutical proof-of-concept in vivo.”
January 2017
“My lab is working on a novel kinase for which no pharmacological tools are available. In our search for an antagonist, we had already performed a small-scale screen that did not identify a compound with sufficient potency to build on. We then turned to the EU Lead Factory, which offered an exceptionally large screen without a fee for service: a unique opportunity for an academic researcher as it is difficult to find dedicated grants for exploitation purposes.
The experts from the EU Lead Factory were very proactive, in particular after the initial high-throughput screen. They defined the need within the programme and developed and performed deselection and orthogonal assays which convincingly confirmed target involvement. The hit compounds on the Qualified Hit List have good IC50 values.
Together we have continued to work on downstream characterization of the antagonists in terms of selectivity profiling and pharmacodynamics properties in cell systems. I have been highly involved in the programme from the beginning, and the synergy in competencies between my lab and the EU Lead Factory has given the project a big push forward.”
December 2016
“My time as part of the European Lead Factory was not only stimulating, challenging and enjoyable, but it was also instrumental in securing me a job as a medicinal chemist in industry.
Despite completing a strong and successful PhD in synthetic organic methodology, my appeal to potential employers was minimal due to a lack of complex molecule synthesis and limited medicinal chemistry knowledge. During my postdoctoral position within the European Lead Factory I worked on numerous and diverse complex molecular scaffolds, which employed a wide variety of fundamental chemical reactions. The emphasis on developing molecular libraries with optimal physicochemical properties provided me with an invaluable introduction to modern medicinal chemistry, and the basic principles that all medicinal chemists strive to adhere to when designing molecular targets.
I strongly believe that it was my experience within the European Lead Factory and prioritising optimal physicochemical properties that secured me the job over other strong candidates, and I continue to use these principles on a daily basis.”
December 2016
“At the start of my PhD-project, I screened a commercial library to find hits for our target. The de-selection took a lot of time. In the end, none of the hits from this library could be confirmed at all. My supervisor, Dr Mario van der Stelt, applied for a screening slot at the European Lead Factory, which gave my research a flying start. The expertise in assay development and the access to very high quality drug-like compounds in the screening collection is unique; you can’t find it anywhere else. I learned a lot from the assay development approach.
Working with the EU Lead Factory not only accelerated my research, but more importantly it gave other young researchers good starting points as well. In our research group currently three PhD students and several master students are working with the Quality Hit List retrieved from the EU Lead Factory. The EU Lead Factory doesn’t just boost a single drug discovery project; but it can boost the research of several people. My advice to other academics with a high quality assay: apply for the EU Lead Factory as soon as possible!”
December 2016
"We had identified what we believed was a good target, but we did not have the resources to run high-throughput screening. That’s when we became aware of the European Lead Factory. We were pleased to experience that the process of submitting a proposal was easy and straightforward.
After a substantial amount of preliminary work, we optimized our assay for 384-well-plate use in collaboration with the EU Lead Factory. Together, we also defined the criteria by which the hit list was composed; I was impressed with the amount of thought that went into these processes. The screen identified chemotypes that we had and hadn’t anticipated, and complementary validation assays were carried out by the EU Lead Factory and in our own laboratories.
At present, we are collaboratively optimizing characteristics of promising compounds; we hope to start resistance testing in an in vivo context within a year. Overall, we are extremely satisfied with the progress, from assay optimization to post-hit validation.
The EU Lead Factory really offers a collaborative effort rather than a service, with an exemplary level of commitment and professionalism from the EU Lead Factory scientists.”
November 2016
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