MMV048

MMV048

MMV048 is a novel antimalarial compound from the aminopyridine class, with important activity across the entire parasite lifecycle. The compound was researched by an international team led by Prof. Kelly Chibale from the University of Cape Town, South Africa and was the first new antimalarial medicine to enter phase I studies in Africa.

Dr Cristina Donini explains her vision for MMV048, as well as the importance of getting the formulation right and building clinical trial capacity in Ethiopia.

1. What is your vision for MMV048?

Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase

Tanya Paquet,  Claire Le Manach,  Diego González Cabrera,  Yassir Younis,  Philipp P. Henrich,  Tara S. Abraham,  Marcus C. S. Lee,  Rajshekhar Basak,  Sonja Ghidelli-Disse,  María José Lafuente-Monasterio,  Marcus Bantscheff,  Andrea Ruecker,  Andrew M. Blagborough,  Sara E. Zakutansky,  Anne-Marie Zeeman,  Karen L. White,  David M. Shackleford,  Janne Mannila,  Julia Morizzi,  Christian Scheurer,  Iñigo Angulo-Barturen,  María Santos Martínez,  Santiago Ferrer,  Laura María Sanz,  Francisco Javier Gamo,  Janette Reader,  Mariette Botha,  Koen J. Dechering,  Robert W. Sauerwein,  Anchalee Tungtaeng,  Pattaraporn Vanachayangkul,  Chek Shik Lim,  Jeremy Burrows,  Michael J. Witty,  Kennan C. Marsh,  Christophe Bodenreider,  Rosemary Rochford,  Suresh M. Solapure,  María Belén Jiménez-Díaz,  Sergio Wittlin,  Susan A. Charman,  Cristina Donini,  Brice Campo,  Lyn-Marie Birkholtz,  Kirsten K. Hanson,  Gerard Drewes,  Clemens H. M. Kocken,  Michael J. Delves,  Didier Leroy, David A. Fidock,  David Waterson, 
Leslie J. Street and Kelly Chibale

Science Translational Medicine

DOI: 10.1126/scitranslmed.aad9735

Abstract

As part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of small molecules as a good starting point to develop new antimalarial drugs. Stemming from this series, we found that the derivative, MMV390048, lacked cross-resistance with current drugs used to treat malaria.

MMV390048 - A novel antimalarial compound

A novel antimalarial compound from the aminopyridine class, MMV390048, was awarded MMV's Project of the Year. Dr Cristina Donini took over as Project Director in July 2012, when the compound was selected as a candidate. She tells us what's next for this compound.

1. What is exciting about MMV390048?

MMV390048 - Project of the Year

A novel antimalarial compound from the aminopyridine class, MMV390048, becomes the first researched in Africa to enter preclinical development. Kelly Chibale, Project Leader of the UCT team speaks about the compound and the collaboration with MMV. 

1. What is special about the collaboration that identified the compound?

UCT-H3D, MMV and international partners identify second potent antimalarial candidate

The University of Cape Town (UCT)’s Drug Discovery and Development Centre, H3D, has identified a new potent antimalarial development candidate with potential for both treatment and prevention of malaria.

The compound, referred to as UCT943, is the second preclinical candidate to come out of the collaboration led by H3D involving the Switzerland-based Medicines for Malaria Venture (MMV) and an international network of partners.

MMV048

 

Product vision
  • Part of a single-exposure radical cure

  • Potential for chemoprotection

MoA
  • PfPI4K inhibitor

Key features
  • 80mg dose predicted to give coverage above Minimal Parasiticidal Concentration for ≥8 days

  • Good prophylactic activity against P. cynomolgi, in vivo after single dose 

  • Long half-life in human

  • Potential for transmission-blocking activity in a Standard Membrane Feeding Assay

Challenges
  • Preclinical safety limiting further dose escalation in patients

Status
  • Phase I and human volunteer challenge model completed (including with new formulation)

  • FPFV Phase IIa in Ethiopia (end 2017)

Next milestone
  • De-risk safety margin in preclinical species to allow further dose escalation in patients

 
Previously
  • Name MMV390048: Discovery and Phase I partnership with H3D, University of Cape Town
MMV Project Director
  • Dr Cristina Donini

MMV390048

MMV390048 is a novel antimalarial compound belonging to the aminopyridine class. In combination with a partner drug, MMV390048 has the potential to become a new child-friendly treatment for uncomplicated malaria that could be given as one single dose, completing the treatment in just one day instead of the current three days.

MMV048

MMV048 is a novel antimalarial compound from the aminopyridine class, and the first new medicine to be discovered by an African-led team. In 2014, it entered phase I. This is the first time a new antimalarial has entered volunteer studies in Africa. MMV048 is highly potent against the blood-stage of malaria – active at doses of less than 100 mg, so at this stage it appears to be at least 10-fold more potent than many medicines used today. As such, it could be a really important part of a single-exposure cure.

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