ELF project member spotlight: James Duffy, MMV

11 January 2021

Dr James Duffy is a Director of Drug Discovery at the Medicines for Malaria Venture (MMV), a not-for-profit product development partnership (PDP) working to reduce the burden of malaria by discovering, developing and delivering new, effective and affordable antimalarial drugs. MMV has been partnering with the European Lead Factory (ELF) since 2018 to run high-throughput screens for novel antimalarials. We spoke with James about his experience of working with ELF, the importance of investing in early drug discovery, and the progress made to date with the MMV-ELF screening programmes.

Can you tell us about your collaboration with ELF?
We have always been excited by the opportunity to screen high-quality, novel drug molecules and were delighted to have been given an avenue to access this in a practical way through the European Lead Factory. We have been partnering with ELF since 2018 and to date, we have run two screening programmes. The first was a phenotypic screen to measure the inhibition of parasite growth in red blood cells in response to compounds. The second was a screen against an essential, validated Plasmodium biological target – in line with renewed interest and opportunities for target-based malaria drug discovery projects. Both screens are being run at Pivot Park Screening Centre (PPSC) in the Netherlands.

ELF provides exciting opportunities for the advancement of anti-malarial drug discovery. We joined ELF as an associate member of the European Federation of Pharmaceutical Industries and Associations (EFPIA) group of partners with a long-term financial commitment. As the only PDP on board the ELF project (so far), MMV provides a fresh perspective on the importance of progressing drug candidates for neglected diseases and other non-commercial indications.

Is it unusual for MMV to make this type of long-term financial commitment?
Yes, this is a different model if you consider what we’ve done in the past. But as a proposition, it is perfectly consistent with a lot of things we very much believe in at MMV. The idea of a high-quality, novel, drug-like screening library that isn’t ‘off-the-shelf’ from a commercial vendor is very exciting to us, particularly given the cost effectiveness of the model. Everyone wants to have access to these kinds of chemical starting points. Doing this in a collaborative professional model, based around sharing of information, data, and know-how, really complements our approach to drug discovery. It was a perfect match.

What has been the progress made to date in terms of screening?
The screening part of the first programme was completed in the first part of 2020, and the primary screen for the second programme was finished towards the end of last year. We are therefore on track to complete two screens in the first two years of the ELF-MMV partnership. For our first screen, I’m expecting that we will soon receive the Qualified Hit List of up to 50 compounds. We’re very excited to start the hit-to-lead phase of the project.

Apart from the tangible outcomes of the screens, are there any other less tangible outcomes that you can identify?
Absolutely. I think it’s very important to be part of the wider European ecosystem of drug discovery and expand our network. The links provided with the technical transfer and the new screening groups is extremely valuable. It really does help to have a seat at the table. It keeps infectious and neglected tropical diseases on the agenda and provides extra weight for these disease areas. And of course, the input we receive from other experts is also of importance.

What is your experience of working with consortia like ELF?
This is a natural environment for MMV. Everything we do is done in partnership. Knowing that things are done collaboratively and that you are accountable to the stakeholders and have shared plans and visions for projects suits us very well. The projects have been encouraging for us and working with the coordinating partner Lygature and the other collaborators has also been very positive.

What do you think consortia like ELF bring to anti-parasitic drug discovery?
They are a hub for making drug discovery happen. They bring together international leaders and provide a safe space for the exchange of knowledge and data. They connect experts with different skill sets, helping to establish a robust research network of public and private partners focused on drug development. We can help build compelling cases to encourage funders to support consortia like this with the confidence that they will deliver.

In the past year, COVID-19 has affected everyone. Did it impact on the progress of your screening programmes?
To some extent, yes, but for the most part we were able to proceed with workflows as usual. We are always modifying our screening cascade as new assays and new thinking comes in. There are therefore times when we’ve had to change track somewhat and re-focus our efforts. Perhaps one of the advantages for us last year was our collaboration with industry partners. Thought had been given by the CROs as to how to keep things moving during the pandemic and how to effectively work within the constraints. As such, we were able to manage the impact of COVID-19 on our drug discovery objectives.

Why should funders invest in early drug discovery?
There are many reasons to invest in drug discovery in non-commercial therapy areas, especially infectious diseases impacting the vulnerable, such as malaria. Firstly, COVID-19 has highlighted the fragility of our shared public health, particularly concerning the impact and transmission of infectious pathogens. It is important to stress that the impressive progress in 2020 with COVID-19 vaccines and other interventions would never have been possible without many years of unsung, sustained funding in the technologies, approaches, and thinking to address such a problem – in short in early drug discovery research. Secondly, given the lack of commercial incentives for companies to deliver life-saving medicines and interventions for such diseases, completely new models to fund research and development are needed. Without the moral leadership and funding from global partners in drug discovery and the translation of these discoveries to patients, we risk an inevitable increase in the mortality, morbidity and economic burden on those who can least afford it. We need funding mechanisms, and we need experts to be able to bridge between the brilliant biological idea and the medicine that the clinician is going to give to the patient. This is a vacuum that a lot of projects operate within and it’s something that consortia like ELF try to fill. Without these kinds of programmes, I don’t know how work like this would progress. We’re hopeful that the world of COVID-19 has changed this, and that more investment will be placed in infectious disease research. Only time will tell.

*This interview was first featured on the Lygature website on 18 December 2020.