One molecule: multiple lifecycle stages - MMV's perspective

2014
Dr Paul Willis, Director, Drug Discovery & Dr Lidiya Bebrevska, Associate Director, Translational Medicine, MMV

This molecule has caused a stir among researchers the world over. DDD498 has potent activity against multiple stages of the malaria parasite’s lifecycle, giving it the potential to cure and stop the spread of the disease as well as protect people, all in a single-exposure.

In recognition of the molecule’s promise and the dedication of the team at the Dundee DDU, the project has been named MMV Project of the Year 2014.

 

Dr Paul Willis, Director, Drug Discovery at MMV, and Project Director for the discovery of DDD498 explains how the team came together to discover the compound.

Who were the key partners in the discovery and research of the compound?

The core team involved scientists from the DDU, University of Dundee, working in collaboration with MMV. Dundee has built an academic unit that combines medicinal chemistry, biology and drug metabolism. There are very few academic institutions that integrate these core areas of expertise needed for drug discovery. Working with such a multi-skilled team certainly helped the project to progress quickly.

Leading malaria researchers from MMV’s global network also contributed in various ways, for example, when it came to testing the compound against the various stages of the parasite’s lifecycle. In particular, the whole team benefited greatly from the vast drug discovery experience of Sir Simon Campbell, a member of MMV’s ESAC. Also, contributions from Prof. Julian Rayner of the Wellcome Trust Sanger Institute and Prof. David Fidock of Columbia University were instrumental when it came to understanding the novel mechanism of action.

 


 

Dr Lidiya Bebrevska, Associate Director, Translational Medicine and MMV Project Director for the translational research phase of DDD498 summarizes recent progress and the next steps.

How is the project progressing and what are the next steps?

In 2013, MMV selected DDD498 to enter preclinical development, following recommendation from ESAC. Since then, MMV has been conducting a series of translational activities to progress the compound to early clinical studies in humans. First, ensuring we have sufficient volume of the compound as a drug product of quality suitable for clinical use. Second, ensuring there are no toxicity issues prohibiting dosing in healthy volunteers and estimating the safety limits in humans. Third, planning to start phase I studies and the work on the Controlled Human Malaria Infection Model in Queensland in 2016.1

In addition in 2014, MMV’s business development team worked on identifying a development partner for this project, a company to work with MMV and take the project forward through clinical development.

 


1. Controlled Human Malaria Infection Model: enables candidate medicines to be tested for blood-stage activity in volunteers inoculated with a small dose of malaria in a tightly controlled environment.