DNDi: New Drugs for Neglected Diseases; New Hope for Forgotten Patients

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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dOverview

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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dDisease Landscape

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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dDisease Landscape

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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dBudget

$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!