1 Evolution of MMV Portfolio. 2 MMV Portfolio May 2000-2001 Dihydroorotate dehydrogenase inhibition (DHOD) Dihydrofolate reductase (DHFR) Falcipains Lactate.

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Presentation transcript:

1 Evolution of MMV Portfolio

2 MMV Portfolio May Dihydroorotate dehydrogenase inhibition (DHOD) Dihydrofolate reductase (DHFR) Falcipains Lactate dehydrogenase project (LDH) ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Synthetic peroxide (OZ) Haem Polymerization

3 MMV Portfolio May DHOD DHFR LDH ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Falcipains Synthetic peroxide (OZ) Isoquine (4- aminoquinoline) Intravenous Artesunate 3rd Generation Antifolate Pyronaridine Artesunate LapDap™ Artesunate Haem Pol Artemisone (semi-synthetic endoperoxide) Pf-PFT Fatty acid biosynthesis (FAS II)

4 MMV Portfolio May DHFR ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Falcipains Synthetic peroxide (OZ) Isoquine Intravenous Artesunate 3rd Generation Antifolate Pyronaridine Artesunate LapDap™ Artesunate Artemisone Pf-PFT FAS II

5 MMV Portfolio Dec DHFR ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Synthetic peroxide (OZ) Isoquine IV Artesunate 3 rd Generation Antifolate Pyronaridine Artesunate LapDap™ Artesunate Artemisone FAS II Pf-PFT Falcipains Pediatric Coartem ® GAPDH 4(1H)- Pyridones New dicationic molecules DB289 Fab I PDF 8-amino quinoline Manzamine A DHA Piperaquine Novel Tetracyclines

6 DHFR ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Synthetic peroxide (OZ) Isoquine Intravenous Artesunate Pyronaridine Artesunate LapDap™ Artesunate Artemisone FAS II Pf-PFT Falcipains Pediatric Coartem ® GAPDH 4(1H)- Pyridones New dicationic molecules DB289 PDF Novel Tetracycline Manzamine Alkaloids IV Artesunate MMV Portfolio May amino quinolines Fab I DHA Piperaquine

7 MMV Portfolio Jan DHFR ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Synthetic peroxide (OZ) PO&IV Isoquine ) Pyronaridine artesunate LapDap™ Artesunate Pf-PFT Falcipains Pediatric Coartem ® 4(1H)- Pyridones New dicationic molecules DB289 Fab I DHA Piperaquine 8-amino quinolines Back Up Pyridones 2nd Generation (OZ) Artemifone

8 Peptide deformylase inhibitor (PDF) MMV Portfolio Jan DHFR ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Synthetic peroxide (OZ) PO&IV Isoquine Pyronaridine artesunate LapDap™ Artesunate Pf-PFT Falcipains Pediatric Coartem ® 4(1H)- Pyridones New dicationic molecules DB289 Fab I DHA Piperaquine 8-amino quinolines 8-amino quinolines Back Up Pyridones 2 nd Generation (OZ) Artemifone

9 Structural Component 2000-Date DHFR ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Chlorproguanil- Dapsone (LapDap™) Artesunate FAS II Pf-PFT Falcipains Fab I PDF GAPDH DHODH LDH

10 4 th Call for Proposals 81 new proposals 10 Projects short-listed in Nov.`04 5 projects recommended for funding by ESAC this week MMV to decide on funding soon

11 MMV Portfolio March 2005 DHFR ExploratoryDiscovery PreclinicalClinical Development LeadLeadTransitionPhase IPhase IIPhase III IdentificationOptimization Synthetic peroxide (OZ) PO&IV Isoquine ) Pyronaridine Artesunate LapDap™ Artesunate Pf-PFT Falcipains Pediatric Coartem ® 4(1H)- Pyridones New dicationic molecules DB289 Fab I DHA Piperaquine 8-amino quinolines Back Up Pyridones 2nd Generation (OZ) Artemifone

12 Project Selection Round 1Round 2Round 3 Europe Co-investigators87 Institutions68 North America Co-investigators59 Institutions47 Developing Countries Co-investigators64 Institutions56 Total Countries Institutions947790

13 The Win/Win Proposition Joint R&D MMV Input $$$ Background IPR Link to RBM Expertise Pharma Input Chemistry IPR* Toxicology Management Know How Assets in Kind Technology Liability for Development Risk MMV Gets Rights in DEC IPR in ‘Field’ Drug Supply Return on non DEC Sales Pharma Gets Rights in non DEC IPR outside ‘Field’ PR Benefit HR Benefit Public Private

14 Future Challenges for MMV Funding to support large number of Clinical Studies Shortage of GCP clinical sites for trials Development & Registration of combination therapies Delivery strategy for effective use and health impact

15 MMV a small team, but … Year Scientists Engaged

16 Proposed profiles of new drugs - for uncomplicated malaria Efficacy against drug resistant strains Cure within three days Safe in pregnancy Appropriate formulations and packaging Low cost of goods Further profiles Intermittent treatment in pregnancy & early infancy P. vivax malaria Severe malaria Prophylaxis Single dose cure!!

17 Drug Discovery Process Nwaka & Ridley 2003