dndi: new drugs for neglected diseases; new hope for forgotten patients
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New Drugs for Neglected Diseases
New Hope for Forgotten Patients
Jana ArmstrongExecutive Director, DNDi North America
Partnering for Cures 2009Thursday, Dec 3, 2010
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Drugs for Neglected Diseases initiative
Neglected Patients• 1 billion people
afflicted• 530,000 deaths/year• Poor, marginalized
populations
Most Neglected Diseases• Ineffective, toxic, expensive, archaic
treatments• No financial incentives to motivate
profit-driven pharma industry• Insufficient public sector leadership
• Non-profit drug R&D organization• Addressing the needs of the most neglected patients• Harnessing resources from public institutions,
private industry and philanthropic entities• Three new treatments delivered since 2003
DNDi: an alternative model for drug development“an experiment borne out of extreme frustration about health care for the poorest”
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Neglected Tropical Diseases (NTDs)
• 13 diseases that affect the poorest populations in remote, rural areas, urban slums or conflict zones
• Urgent patient needs: – improve access & improve innovation
• DNDi Focus: innovation for the most neglected patients and diseases– Comprehensive drug development strategy for “most neglected”
diseases– Respond to patient needs for efficacious, safe and accessible
treatments
Visceral Leishmaniasis (VL)
Sleeping Sickness (HAT)
Chagas Disease Malaria
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Current Treatment Limitations
Patients and Healthcare Workers Need Safe, Effective, Easy-to-Use Drugs
Melarsoprol (arsenic-based IV drug) “Fire in the Veins”
Benznidazole: adult tablets fractioned or macerated for pediatric use
• Ineffective (resistance)• Toxic• Expensive• Painful when delivered• Difficult to use (i.e. IVs requiring round-
the-clock nursing)
• Not registered in endemic regions• Restricted by patents• Lack of pediatric formulations
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Human African Trypanosomiasis (HAT) or Sleeping Sickness
• 60 million at risk in sub-Saharan Africa
• Transmitted by the tsetse fly
• Difficult to diagnose; many patients go undiagnosed until late stage of disease
• Fatal if untreated
• Needs:
• A safe, effective, and practical stage 2 treatment
• A simple stage 1 treatment
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Visceral Leishmaniasis (VL)
• 200 million at risk worldwide (in 70 countries)
• Transmitted by the sandflies• Symptoms: prolonged fever, enlarged
spleen & liver, substantial weight of loss, progressive anemia
• Fatal if untreated• Current drugs: antimonials, Amphotericin B,
AmBisome®, miltefosine, paromomycin• Needs:
• Oral, safe, effective, low-cost and short-course treatment
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Disease LandscapeChagas Disease: A Silent Killer
• 100 million at risk in Latin America• Kills more people in region than malaria• Patient number growing in non-endemic,
developed countries • Transmitted by ‘kissing bug’, blood transfusion,
organ transplantation, as congenitally or orally• Majority of patients undiagnosed until late
stage• 30% will develop life-threatening heart
disease or gastrointestinal complications• Needs:
• An affordable, age-adapted, safe, and efficacious paediatric strength
• A new drug for early chronic stage
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Market LandscapeA Fatal Imbalance
• World pharmaceutical market $712 billion in 2007*
• Market-driven, private enterprise focused on ROI and profitable drugs
• Neglected Diseases:– affect poorest populations in
developing countries– lie outside the world “market”– patient needs remain
unaddressed due to market and public policy failures
*Source: IMS Health, 26.2.2008Chart Data Source: Chirac P, Torreele E. Lancet. 2006 May 12; 1560-1561.
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Source: Moran et al., G-Finder report, 2009
Market LandscapeGlobal R&D funding in 2007
0.51.8
7.3
21
69.4
Public(governments)
Not-for-profit
Big pharma
Small pharmaand biotech
Other
0.9
4.1
54.3
36.7
3.9
Public (IDCgovernments)
Public (OECD-plusgovernments)
Not-for-profit
Private (multi.pharmacompanies)
Other
Neglected Diseases $2.5 billion (US)
Kinetoplastids$125 million (US)
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Brazil
India
KenyaMalaysia
USA
DRC
Japan Geneva Coordination Team + consultants
7 Founding Partners• Indian Council for Medical
Research (ICMR) • Kenya Medical Research Institute
(KEMRI)• Malaysian MOH• Oswaldo Cruz Foundation Brazil• Medecins Sans Frontieres (MSF)• Institut Pasteur France• WHO/TDR (observer)
7 worldwide offices
DNDi “Business” Plan & OrganizationObjectives• Deliver 6 - 8 new treatments by 2014 for neglected diseases, with robust pipeline (malaria,
Chagas, sleeping sickness, leishmaniasis)• Use and strengthen research capacity in disease endemic countries• Raise awareness and advocate for increased public responsibility Key features• Patient-needs focused• Founding partners and governance include research institutes in disease-endemic countries• R&D project management team with strong pharma, biotech, drug development experience• Global but lean core team managing a variety of partnerships & consultants
• 120+ scientific partners, including large pharmaceutical firms, small biotechs, universities, and public institutions
• Investment required: ~$400M / diversified sources
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Strategy
Long-Term projects
Medium-term projects
Short-term projects
New compoundsScreening of
existing libraries>6 years
Therapeutic switch“Rediscovered” compounds
3-6 years
New formulations (FDC)Geographical extensions
Co-administration 3 years
R&D StrategyDNDi Portfolio-Building Model
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Exploratory
Alternative formulations Amphotericin B (VL)
6 to 8 new treatments
Drug combination (Chagas)
Oxaborole (HAT)
Nitroimidazole backup (HAT)
Fexinidazole (HAT)
ASAQ (Malaria)
Fixed-Dose Artesunate/
Amodiaquine
ASMQ (Malaria)
Fixed-Dose Artesunate/Mefloquine
Combination therapy (VL in Asia)
Paediatric benznidazole(Chagas)
Azoles (Chagas)
Exploratory
Combination therapy (VL in Africa)
• Paromomycin• AmBisome®• Miltefosine
8-aminoquinolines – in preparation (VL)
• Sitamaquine • Tafenoquine
Combination therapy
(VL in Latin America) – in preparation
NECTNifurtimox - Eflornithine
Co-Administration
Stage 2 HAT
2 HAT LO Consortium•Scynexis •Pace Univ
Chagas LO Consortium•CDCO•Epichem•Murdoch Univ
VL LO Consortium•Advinus•CDRI
Reference screening centres:LSHTM, Swiss Tropical Institute, University of Antwerp
Exploratory
a robust pipeline
• Compound mining
E.g.: nitroimidazoles, …• Chemical classes
E.g.: macrolides, GSK, Merck, …
• Target-based
E.g. Dundee’s Drug Discovery Unit (DDU), …
• Screening
E.g. natural products (Kitasato, Eskitis), new technology (Institut Pasteur Korea), DDU at Dundee, …
R&D StrategyRobust Portfolio – November 2009
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AccomplishmentsDNDi 6-Year Results
• 2 new malaria treatments delivered• 1 new sleeping sickness combination delivered• Largest pipeline ever for the kinetoplastid diseases• Clinical research platforms in Africa• $187M of $410M needed raised• On track to deliver new treatments per business plan
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ASAQ (Malaria)Fixed-Dose Artesunate/
Amodiaquine
NECT (HAT)Nifurtimox - Eflornithine
Co-Administration
ASMQ (Malaria)Fixed-Dose Artesunate/Mefloquine
Accomplishments3 New Treatments Delivered
Farmanguinhos(Brazil)
Cipla (India)
sanofi-aventis(France)
National Control Programs
MSF
WHO
2007
2008
2009
Partners
• Easy to Use
• Affordable
• Field-Adapted
• Non-Patented
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$187M of $410M Secured (2003-2014)
Private Donors• Médecins Sans Frontières (€29 M)• Bill & Melinda Gates Foundation
(€42M)• Other Private Foundations Public Donors• United Kingdom - DFID (€29 M)• France – AFD & MAEE (€8 M)• Spain – AECID (€7.5 M)• Netherlands – DGIS (€3 M)• USA – NIH/NIAID (€1 M)• Germany – GTZ (€1 M)• Switzerland - Canton de Genève & DDC• European Union - FP 5, 6,7• Italy - Region of Tuscany
Funding Strategy: Independence through diversified sources of funding•Approximately 50% of funding from public institutional donors in line with DNDi’s advocacy objective (public responsibility for NDs)•Approximately 50% from private sector (foundations, major donors, general public)•Key contributions to come from Founding Partners•Maximum of 25% per donor
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Budget~$223M Still Needed for 3-5 More Treatments2004-2014 Projected (€):
www.dndi.org
By working together in a creative way, we can bring innovation to neglected patients!
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