1. DNDi Olaf Valverde Mordt Trondheim, 14 March 2017 GLOBVAC Conference
Drug development for African Trypanosomiasis
DNDi model for innovation and access
Olaf Valverde Mordt
Trondheim, 14 March 2017
GLOBVAC Conference

2. DNDi’s Mission
Develop new drugs or new formulations of existing drugs for people living with neglected diseases
Commitment to most neglected diseases and take on new disease areas
Strengthen capacities in a sustainable manner
Adopt a dynamic portfolio approach with new operating models

3. DNDi’s PRIORITY: Neglected Patients
Responding to the Needs of Patients Suffering from Neglected Diseases…
© Sa'adia Khan-MSF
Hepatitis C
Sleeping sickness
DNDi’s PRIORITY: Neglected Patients
Malaria
Mycetoma
Chagas disease
Paediatric HIV
Filarial diseases
Leishmaniasis
…from Bench to Bedside

4. Address immediate patient needs & deliver innovative medicines:
Short- and long-term
New chemical entities
(NCEs)
New formulations
New indications for existing drugs
Completing registration dossier
Geographical extension
Long-
term projects
Medium-
term projects
Short-term projects
Research
Translation
Development
Implementation
Development
> 5 years
3-5 years
1-2 years

5. By 2023: Deliver 16 to 18 treatments with EUR 650 million
2016
7 treatments delivered
2023
9 -11 additional treatments delivered
2023
16-18 treatments
Develop treatments for people suffering from neglected diseases
Strengthen research capacity, led by Regional Offices
Influence the R&D landscape for neglected patients
Political leadership for needs-driven R&D
Creation of a global fund and mechanism
Evidence on alternative R&D models
R&D platforms in disease-endemic countries
Regionally-driven initiatives
Patient access to treatments
Transfer of technology
Deliver treatments
3 new chemical entities (NCEs)
~10 disease areas
Focus on access and measure impact

6. Nifurtimox-Eflornithine Combination Therapy Paediatric Dosage Form
DNDi R&D Portfolio
7 new treatments available and up to 15 new chemical entities in the pipeline
Research
Translation
Development
Implementation
Screen
Hit to Lead
Pre-clinical
Phase I
Phase IIa/PoC
Lead Opt.
Registration
Phase IIb/III
Access
SCYX
SCYX
oxaborole
SCYX-7158
oxaborole
Fexinidazole
NECT
Nifurtimox-Eflornithine Combination Therapy
HAT
Screening
Leish H2L
DNDI-5421 DNDI-5610
oxaborole
DNDI-6148
oxaborole
New Treatments for HIV/VL
SSG&PM
Africa
DNDI-0690
nitroimidazole
New Treatments for PKDL
Amino
pyrazoles
New VL Treatments
Asia
Leishmaniasis
MF/Paromomycin Combo for Africa
CGH VL Series 1
New VL Treatments Latin America
CpG-D35 (CL)
New CL Combination
Screening
Chagas H2L
Chagas Lead Opt
New Benz Regimens +/- fosravuconazole
Benznidazole
Paediatric Dosage Form
Chagas
Biomarkers
Fexinidazole
Filaria
Screening
Macro Filaricide 3
ABBV-4083
TylaMac
Emodepside
Two ‘4-in-1’
LPV/r/ABC/3TC
LPV/r pellets with dual NRTI
Superbooster Therapy
Paediatric HIV/TB
Pediatric HIV
HCV
Ravidasvir/
Sofosbuvir
Malaria
FDC ASAQ
Mycetoma
Fosravuconazole
Malaria
FDC ASMQ
December 2016
New Chemical Entity (NCE); Fexinidazole (for HAT and Chagas disease) = 1 NCE; Fosravuconazole = 1NCE

7. 7 new treatments delivered, recommended, implemented
30 projects, 8 diseases areas
13 entirely new chemical entities (NCEs)
Over 160 partnerships, most in endemic countries
160 staff, half in endemic countries & 700 people working on DNDi projects
EUR 400 million raised equally from public and private sources
4 regional disease-specific clinical trial platforms/ networks and several technology transfers
2016
SUPERBOOSTER
THERAPY P
aediatric HIV/TB HI V
/TB
Easy to use
Affordable
Field-adapted
Non-patented

8. Paediatric HIV: Scaling up with the right tools, right now and bringing ‘4-in-1’s formulations for children
Today
LPV/r Only available treatment for young children: unpalatable (42% alcohol), requires refrigeration, expensive, difficult to store and transport
2016
‘Super-boosting’ ritonavir is recommended by WHO in ARV guidelines 2016 for TB/HIV co-infected children
By 2018
To deliver:
2 new ‘4-in-1’s child-appropriate formulations that are safe, easy to administer, well-tolerated & heat-stable

9. DNDi’s success: Only possible through innovative partnerships
CROs
Int. Org/ NGOs
MoH/
Gov/
Hospitals
Universities/ Research institutes
Pharmas/Biotechs
PDPs
Over 160 partnerships worldwide
Criteria for Success:
Share the same vision
Mutual understanding
Involvement throughout the
whole process

10. Partnering and research capacity building with
MoHs and national control programmes VL
Major Role of Regional Disease Platforms:
Strengthening local capacities
Conducting clinical trials (Phase II/III studies)
Facilitating registration
Accelerating implementation of new treatments (Phase IV & pharmacovigilance studies)
Defining patients’ needs and target product profile (TPP)

11. Cost of developing drugs: DNDi model

12. Geographic distribution of HAT cases
( )
T.b.
rhodesiense
T.b.
gambiense

13. Illustration of DNDi model for innovation and access: Drug development for Sleeping Sickness
From toxic drugs and long treatments towards a medicine for use at village level
13 years ago
Melarsoprol:
Toxic, resistant
Eflornithine:
Unavailable
Since 2009
NECT Improved therapy
2018?
Fexinidazole
Oral treatment (10 days)
Future objective
SCYX-7158
Single-dose,
oral treatment

14. DNDi’s First NCE to Reach Phase II/III Endpoint
New Chemical Entity ∙ New Chemical Entity
DNDi’s First NCE to Reach Phase II/III Endpoint
NCE
DEVELOPMENT
2007: Selection of fexinidazole as pre-clinical candidate for HAT
2008: Pre-clinical development completed. Prototype tablets available
2009: Phase I starts in France
2010: Phase I completed
2012: Phase II/III starts in DRC and CAR. Sanofi industrial partner. Comparing fexinidazole vs NECT in patients with stage 2
2015: Phase II/III inclusions completed. Inclusion of 394 patients. 2 additional studies for stage 1 and early stage 2 (230 p.) and children (125 p.) patients also completed recruitment.
2016: Endpoint for submission reached for the 3 studies + start of an implementation study in outpatients
Phase IIb/III
Registration
Fexinidazole
Objective: Develop and register fexinidazole as a new drug for the treatment of stage 2 T.b. gambiense, ideally also for stage 1 and for children between 6 and 14 years old
PARTNERS: BaseCon; Bertin Pharma; Venn Life Sciences (previously Cardinal Systems); Cardiabase; Médecins Sans Frontières, and other HAT Platform members; Phinc Development; National Control Programmes of the Democratic Republic of Congo and the Central African Republic; RCTs; Sanofi; Swiss Tropical and Public Health Institute (Swiss TPH); SGS; Theradis Pharma

15. New Chemical Entity ∙ New Chemical Entity
Promising Oral-only Single Dose Treatment for Sleeping Sickness to Enter Phase II/III Clinical Study
NCE
DEVELOPMENT
Identified as hits against T.b. brucei at Sandler Center, University of California San Francisco
Innovative partnership with 2 biotechs (Anacor, Scynexis) and 1 university (Pace) in the US
End 2009: First NCE resulting from DNDi lead optimization programme
2011: Pre-clinical development
2012: Phase I study in France
October 2016: Start of Phase II/III clinical study in DRC in adults with stage 2 HAT
Phase IIb/III
SCYX-7158
Objective: Develop and register
SCYX-7158 as a new drug for the treatment of stage 2 T.b. gambiense, ideally also for stage 1.
PARTNERS: Anacor Pharmaceuticals; Advinus Therapeutics; SCYNEXIS; Swiss Tropical and Public Health Institute; Institute of Tropical Medicine – Antwerp; Institut de Recherche pour le Développement; Institut National de Recherche Biomédicale

16. HAT Platform: overcoming health system challenges by strengthening clinical research capacities
Results since 2007:
Key role in every clinical study led by DNDi
NECT, Fexinidazole, SCYX-7158
Trainings (GCP and others)
728 people trained since 2010
Information sharing
17 newsletters since HAT Platform launch
2 platform meetings/year
Chad
PARTNERS: Over 20 institutions and 120 individual representatives
National HAT control programmes of most affected endemic countries
Research institutes: Swiss TPH, ITM-A, IRD, INRB, CDC, KARI-TRC, TMRI, Institut Pasteur, Bangui
Universities: Makerere, Uganda; Juba, Sudan; Edinburgh, UK
NGOs: DNDi, MSF, Epicentre, FIND
Regional networks: EANETT, PABIN, AMANET, CIBAF, INZI project
WHO-NTD as observer
Central
African Republic
Sudan
South Sudan
Guinea
Uganda
Rep. of
Congo
Dem. Rep. of Congo
Angola

17. Conclusions
Neglected Tropical Diseases require specific interventions to respond to the market failure of drug development for profit
They fit into the WHO road map for NTD elimination by 2020 and the Sustainable Development Goals for 2030 (fight poverty, good health, reduce inequality and promote partnerships for the goals)
Elimination need to be sustainable, to reach this point, innovation and adapted tools (drugs, vaccines, diagnosis) are necessary, including simple, safe, effective and logistically feasible treatments

18. Thank you
Takk

19. THANK YOU
TO ALL OUR
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