MMV welcomes proposals in the following three areas:
1. Compounds addressing the key priorities of the malaria eradication agenda
Novel families of molecules in the hit-to-lead or lead optimization stages are sought without G6PD deficiency liabilities that either:
- kill or reactivate hypnozoites for use as part of a P. vivax radical cure; or
- have activity against sexual stage V gametocytes and evidence of transmission blocking in SMFA.
2. Compounds with activity against asexual liver and/or blood stages
Novel chemical series with EC50<500nM and which have one or more of the following key features:
- A known, novel mechanism of action;
- An inability to select resistant mutants in vitro;
- Activity at more than one life-cycle stage;
- A long half-life (ideally >4h in rodents) and confirmed in vivo efficacy.
For advanced series, we are seeking novel compounds with, ideally, a predicted human half-life >100h and a predicted oral single human dose <500mg or an i.m. dose that can be administered in <0.5mL and sufficient for up to 3 months’ protection in humans.
3. Novel approaches for screening
To help identify new phenotypic and/ or target based hits, as well as confirm activity of MMV compounds on all human malaria asexual blood stages, new screening proposals are sought amongst the three categories below:
- Validated Plasmodium target-based assays, ideally with evidence of target essentiality beyond asexual blood stages. Biological validation should be supported by a biological target based screening assay suited for identification of novel chemical series.
- Novel whole cell phenotypic screening paradigms to potentially identify new relevant chemistry.
- Asexual blood stage assays for vivax, malariae and ovale malaria.
Please see the published MMV Target Candidate Profiles for more information. Early target validation falls outside of our mandate.
MMV also welcomes requests for support to investigate the mechanism of action of compounds:
Compounds for target identification
MMV is working with a consortium funded by the Bill and Melinda Gates Foundation on a project to identify mechanisms of action of compounds having phenotypic activity. Compounds can be considered for such target identification activities provided that the following terms are acceptable:
- The Plasmodium whole cell EC50 <1uM and the chemical structure can be shared.
- A minimum of 10mgs of compound can be provided to the consortium.
- The ongoing studies and data will be discussed with the compound provider but the consortium have permission to publish (with co-authorship from the provider).
A one page Excel template needs to be completed to submit a compound for target ID.
All applications using the specified templates should be sent electronically to proposals [at] mmv.org by 12 noon CET, Friday, 24 March 2017.