Accelerating open drug discovery
1. Why are MMV Open and Malaria Libre considered pioneering approaches to drug discovery?
Open collaboration in research, especially drug discovery, is relatively rare. The advantages are many: researchers collaborating from diverse fields can bring in skills, expertise and facilities, adding immense value to the project. It saves us from reinventing the wheel – for example, it is quite possible that an issue faced in the project has already been addressed and solved by other researchers and their learning can be immediately shared and implemented, thus saving time and resources.
2. What is your role within MMV Open/Malaria Libre?
I am a PhD medicinal chemist with over 20 years of experience, and joined MMV in 2018 to work on MMV Open. I am responsible for building research networks for malaria, particularly in the context of testing MMV compounds such as Open Access Boxes on nonmalaria pathogens for other infectious diseases. I am currently leading the Malaria Libre project, helping to build both the scientific body of knowledge on malaria drug discovery as well as a strong open science community.
3. How does the open science of Malaria Libre fulfil its aim?
The primary aim is to identify a preclinical candidate. In parallel, we are working to build a strong community of next-generation drug discovery scientists committed to collaboration and open sharing of ideas and data. This open approach helps save time and resources. For example, based on the mode of action of a frontrunner compound confirmed by groups at Monash University, Drexel University and Jawaharlal Nehru University (JNU), the team decided to defer medicinal chemistry work on a series until more parasitology data was generated, especially on the propensity to generate resistance that would enable a decision to stop or go ahead with the series.
4. What has Malaria Libre achieved so far and when could it deliver a preclinical candidate to advance into antimalarial research?
Malaria Libre is still at an early hit-to-lead stage, where the hits identified from phenotypic screening are being optimized to identify promising lead compounds. So far, we have been able to build a network of collaborators who have proactively contributed to the project, despite a huge shift towards COVID-19 research. We hope to be able to deliver on our primary goal of a preclinical candidate by 2025, if all goes according to plan, but this is an experiment in a new way of working, so that’s quite an ambitious goal.
5. Malaria Libre is operating out of India and working with several partners across the world – what do they contribute to the project?
India is an important geography for drug research – its drug discovery work boasts a highly competent research community, robust infrastructure and skilled human resources. In India, Malaria Libre launched with the participation of researchers from three institutions: CSIR-Central Drug Research Institute to help synthesize compounds, the Special Centre for Molecular Medicine at JNU to conduct parasitology tests, and TCG Lifesciences to conduct the majority of compound screening, primary assays and syntheses. TCG is also engaged in chemistry work for other MMV projects. Other groups at Monash, Drexel and University of São Paulo have contributed to target deconvolution of the hits that are worked upon and other groups have supported medicinal chemistry. These have been made as in-kind contributions. The project team also has access to all the assay platforms that support the project progression.
6. Does MMV have experience in empowering drug discovery research in other disease areas?
The compound licensed out to Merck from Salvensis1 for preclinical development against schistosomiasis had its origin in one of the MMV Open libraries. In addition, hit compounds identified through screening of open-access compound collections are taken through iterative ‘make-test-analyse’ cycles that design drug candidates for other neglected diseases, like tuberculosis and Chagas.
7. What’s next for MMV Open?
We are anticipating the launch of the Global Health Priority Box (GHPB) in the second half of 2022 in collaboration with the Innovative Vector Control Consortium and Bristol Myers Squibb. Like the previous Open Access Boxes, the GHPB will comprise compounds that have shown promise against malaria or other neglected diseases or for vector control. It will be available free of charge to researchers with the only stipulation that their research is posted in the public domain. Meanwhile, we remain focused on identifying a high-quality preclinical candidate by 2025.
1. A not-for-profit, small molecule drug discovery company with a focus on rare and neglected diseases.
Dr Kirandeep Samby, MMV Open project leader