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ANNUAL
REPORT
2015
Medicines for Malaria
Venture (MMV) is recognized as a leading
product development partnership in the field of antimalarial drug research
and development. It was established as a foundation in 1999
in Switzerland.
MMV’s mission is to reduce the burden of malaria in disease-endemic countries by
discovering, developing and delivering new,
effective and affordable antimalarial drugs.
MMV’s vision is a world in which these
innovative medicines will cure and protect the vulnerable and under-
served populations at risk of malaria, and help
to ultimately eradicate this terrible disease.
© June 2016 Medicines for Malaria VentureAll rights are reserved by Medicines for Malaria Venture. The document may be freely reviewed and abstracted, with a clear and appropriate acknowledgement of source, but is not for sale or for use in conjunction with commercial purposes.
Requests for permission to reproduce or translate the document, in part or in full, should be addressed to the administration of Medicines for Malaria Venture, where information on any translation or reprints is centralized.
MMV Disclaimer This document contains certain forward-looking statements that may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions, or by discussion of, among
other things, vision, strategy, goals, plans, or intentions. It contains hypothetical future product target profiles, development timelines and approval/launch dates, positioning statements, claims and actions for which the relevant data may still
have to be established. Stated or implied strategies and action items may be implemented only upon receipt of approvals including, but not limited to, local institutional review board approvals, local regulatory approvals, and following local laws
and regulations. Thus, actual results, performances or events may differ from those expressed or implied by such statements. We ask you not to rely unduly on these statements. Such forward-looking statements reflect the current views of
Medicines for Malaria Venture (MMV) and its partner(s) regarding future events, and involve known and unknown risks and uncertainties.
MMV accepts no liability for the information presented here, nor for the consequences of any actions taken on the basis of this information. Furthermore, MMV accepts no liability for the decisions made by its pharmaceutical partner(s), the
impact of any of their decisions, their earnings and their financial status.
3
ContentsTooling up to bring malaria down
Message from the Chairman and CEO 4
Key achievements 6
MMV strategic overview 8
MMV-supported projects 9
Working with regulators to advance access to quality medicines
Message from Wendy Sanhai and Wiweka Kaszubska 10
Developing next-generation medicines
Addressing resistance and improving compliance 12
Aiming to stop relapsing malaria with a single-dose treatment 22 Advancing the science of eradication
MMV’s drug discovery engine 25
Opening up malaria drug discovery 26
Open access initiatives to catalyse drug discovery 27
New models to discover new molecules against the relapse 28
MMV Project of the Year 2015: GSK692 30
Getting better medicines to more people
Developing treatment options for children 32
Facilitating sustainable uptake of injectable artesunate 34
Buying time to save lives with rectal artesunate 36
Aiming for elimination 37
Protecting children at their most vulnerable 38
Improving malaria chemoprevention and treatment during pregnancy 39
Financial view 40
Behind the scenes 56
1
2
3
4
5
6
7
1 | Tooling-up to bring malaria down
4
1
Dr David Reddy
CEO
Mr Per Wold-Olsen
Chairman of the Board
Message from the Chairman and CEO
Fired by our mission, in 2015 MMV
tooled up to drive the develop-
ment of new medicines and increase
access to antimalarials for vulnerable
populations – contributing to the global
effort to bring the burden of malaria
down to zero.
The year also marked a key milestone
for the entire malaria community – the
transition from the MDGs to the SDGs.
MMV is proud to have played its part
in the achievement of malaria-related
Millennium Development Goal (MDG)
6.C – to halt and begin to reverse
the incidence of malaria by 2015.
The intensified scale-up of control
measures like bed nets, insecticides
and medicines saved the lives of more
than 6 million people from malaria since
2000, including 5.9 million children
under 5 years of age.1
Yet malaria continues to kill and
debilitate, keeping people entrenched
in poverty and threatening the lives of
young children. More than 300,000
children died from malaria in 2015
alone. The newly adopted Sustainable
Development Goals (SDGs) for 2030
recognize the critical need to pull people
out of poverty into universal health and
prosperity. Stopping scourges like
malaria is one of the cornerstones to
achieving this.
With this end in mind, key global players
recommitted to malaria eradication with
the publication of several far-sighted
reports. The World Health Organization
launched The Global Technical Strategy
for Malaria 2016–2030,2 and the Roll
Back Malaria Partnership launched
Action and Investment to defeat Malaria
2016–2030 (AIM) – for a malaria-
free world.3 Both reports target a
fall of 90% in malaria incidence and
mortality rates by 2030. A plan to
pave the way for malaria elimination
by 2040, From Aspiration to Action,4
was also launched in a joint initiative by
the United Nations Secretary-General’s
Special Envoy for Health in Agenda
2030 and for Malaria, Ray Chambers,
together with the Bill & Melinda Gates
Foundation. In addition, India recently
published its National Framework for
Malaria Elimination.5 Each of these
reports emphasize the need for universal
coverage of core interventions like bed
nets, insecticide sprays, diagnostics
and medicines for all populations at risk.
Increasing the range of high-quality
medicines available to treat these
populations is vital and we are delighted
to report that in 2015 MMV brought
forward another new, high-quality
medicine through registration, bringing
MMV and partners’ total contribution
to six. Child-friendly Pyramax® granules
(pyronaridine-artesunate) (page 32-33)
developed with Shin Poong Pharma -
ceutical received positive scientific
opinion under Article 58 from the
European Medicines Agency and joined
MMV’s first co-developed medicine,
Coartem® Dispersible (artemether-
lumefantrine), as the second stringently
approved paediatric artemisinin-
based combination therapy (ACT).
While much work remains to maximize
the impact of this and other quality
medicines in saving lives, the number
of MMV-supported treatments delivered
continues to rise. For example, in 2015
Coartem Dispersible, co-developed with
Novartis, reached the landmark of 300
million treatments delivered since its
launch.
Looking to the ultimate eradication
of malaria, the strategic reports also
highlight the critical need to develop
new transformational tools, such as
single-dose cures and medicines
to tackle resistance. MMV and its
partners continue to tool up for the
challenge. Of 65 drug development
projects, eight have progressed to
Tooling up to bring malaria down
Mahatma Gandhi
A small body of
determined spirits fired
by an unquenchable faith
in their mission can alter
the course of history.”
“
5
clinical development targeting unmet
needs, including medicines for children,
pregnant women, and people suffering
from relapsing or drug-resistant malaria.
We are developing a new business
plan for the next 5 years and prioritizing
research and delivery activities for the
eradication agenda. Our portfolio of
projects is evolving like never before.
If we are to help the global health
community meet the SDGs by 2030, we
have no time to lose. We are rigorously
testing promising compounds, both
singly and in combination, to ensure
they are fit to progress through the
pipeline. To accelerate the process,
we have begun parallel programmes;
notably artefenomel (OZ439) (page 16)
which, in partnership with Sanofi, was
trialled in combination with piperaquine
(PQP) and also with ferroquine (FQ).
Early indicators showed that the
artefenomel+PQP combination was
unlikely to meet the rigorous criteria for
a single exposure radical cure. While
this setback serves as a reminder that
drug development is complex, risky
and uncertain, MMV was able to rapidly
progress the parallel programme of
artefenomel+FQ while deploying efforts
to other high-potential prospects. These
include DSM265 (page 17), a new
molecule with promise as a single-dose
cure or prophylaxis, which succeeded in
demonstrating initial proof of efficacy as
an antimalarial.
Meanwhile, our partnership network
continues to expand with several new
partners joining the MMV fold: Mitsubishi
Tanabe Pharma, Daiichi Sankyo, OP Bio
Factory Co. and Sumitomo Dainippon
Pharma from Japan and Merck
Serono from Germany. As our network
increases, so does the quantity and
quality of the molecules in our portfolio
alongside the tools and platforms to test
and refine them.
To stay at the cutting edge, we constantly
challenge the status quo. For example,
over the years MMV and partners have
been pioneering more open ways of
working, from publishing screening data
in the public domain in 2010 to launching
the open access Malaria Box, and more
recently the Pathogen Box (page 27).
These two collections of carefully
selected active compounds distributed
for free have proved to be a hit. By
responding to the need for researchers
to access physical compounds, the
projects are helping to catalyse new
drug discovery programmes around the
world. In recognition of this work, MMV
was proud to receive the Tim Berners-
Lee Open Data Innovation Award for the
Malaria Box thanks to a nomination from
the UK Department for International
Development.
Through open research initiatives like
these, as well as sharing our expertise
and resources, MMV’s impact is
stretching beyond the malaria field.
During the Ebola outbreak in West
Africa in 2014–2015, MMV and partners
temporarily stopped a clinical trial in
Guinea yet continued to fund resources
and support the staff thus enabling
them to focus on tackling the outbreak.
Today, the trial’s Principal Investigator is
the focal point for Ebola in Guinea, in
part thanks to the good clinical practice
training he received as part of this
involvement.
As we reflect on 2015, both in terms of
MMV’s progress and that of the wider
malaria community, it’s clear we have
much to celebrate, yet much remains to
be done for the global malaria community
to reach the very ambitious targets it has
set itself. Haunted by the tragedy of
the failed global malaria eradication
campaign in the 1950s and 1960s, in
part caused by waning commitment for
the last-mile push, concerns about the
risk of declining global focus on malaria
remain real until our ultimate goal is
achieved.
MMV’s achievements in 2015 would
not have been possible without the
determination of the team, as well
as the commitment of our donors,
partners and Board of Directors. We are
immensely grateful for this support and
a special debt of gratitude is owed to
Ray Chambers. Ray stepped down after
4 years as Chairman of MMV’s Board of
Directors in 2015, entrusting the role to
Vice Chair, Per Wold-Olsen. Fortunately
for us, thanks to his ongoing role as UN
Special Envoy for Health in Agenda 2030
and for Malaria, MMV will continue to
benefit from his leadership as will the rest
of the malaria community.
The American scholar Warren G Bennis
once said: “Leadership is the capacity to
translate vision into reality.” MMV’s vision
to develop innovative medicines for
vulnerable populations at risk of malaria
is a reality thanks to Ray’s leadership.
Today we are poised to deliver the next-
generation medicines to help change the
course of history and bring malaria cases
down to zero.
1 World Health Organization. World Malaria Report 2015 (2015): http://www.who.int/malaria/publications/world-malaria-report-2015/report/en/
2 World Health Organization. Global Technical Strategy for Malaria 2016–2030, (2015): http://www.who.int/malaria/areas/global_technical_strategy/en/
3 The Roll Back Malaria Partnership. Action and Investment to defeat Malaria 2016–2030 (AIM) – for a malaria-free world (2015): http://www.rollbackmalaria.org/about/about-rbm/aim-2016-2030
4 From Aspiration to Action – What will it take to end malaria? UN Secretary-General’s Special Envoy for Health in Agenda 2030 and for Malaria, Bill & Melinda Gates Foundation (2015): http://endmalaria2040.org/
5 Government of India. National Framework for Elimination of Malaria (2016): http://www.searo.who.int/india/publications/national_framework_malaria_elimination_india_2016_2030.pdf?ua=1
1 | Tooling-up to bring malaria down
6
health-care workers across 1,650 health-care facilities in six
African countries trained to administer injectable artesunate
for severe malaria, via Clinton Health Access Initiative and the
Malaria Consortium in the MMV-led Improving Severe Malaria
Outcomes (ISMO) Project funded by UNITAID
18,000
300 million
medicine for children approved; Pyramax® granules
(pyronaridine-artesunate), co-developed with Shin Poong,
received positive scientific opinion from the European
Medicines Agency via its Article 58 procedure
treatments of Coartem® Dispersible (artemether-lumefantrine) for children,
co-developed with Novartis, delivered
to over 50 countries
New
compounds active against
neglected diseases (the
Pathogen Box) available
for free to boost drug
research
9new medicines in clinical
development prioritizing
eradication and treatment
for vulnerable populations
including children and
pregnant women
ACTs (artesunate-
amodiaquine & artesunate-
mefloquine), developed by
DNDi and partners
transitioned to MMV’s
portfolio
2MMV wins Open Data
Innovation Award for work
on the Malaria Box
1st
400
Key
achie
ve
7
children across the Sahel region benefit from
Seasonal Malaria Chemoprevention using
sulfadoxine-pyrimethamine+amodiaquine,
supplied by MMV’s partner Guilin Pharma
3 million
of investment impact thanks to direct
and in-kind support from partners
USD 1 = USD 3.5
2dossiers for rectal
artesunate suppositories
submitted for WHO
prequalification
by Cipla and Strides
drug candidates brought
forward from discovery
research since 2010
17
doses of Eurartesim® (dihydroartemisinin-piperaquine),
co-developed with Sigma-Tau, distributed in
two ground-breaking mass drug administration
pilots in Zambia and Mozambique
>200,000
2 0 1 5
ments vials of Artesun® (Guilin Pharma’s injectable artesunate)
delivered to treat children with severe malaria, saving
an estimated additional 300,000–350,000
lives compared to quinine treatment
52.9 million
1 | Tooling-up to bring malaria down
8
MMV strategic overview – from malaria control to eradication
To save lives from malaria today
and tomorrow, MMV focuses on
two broad areas: maximizing the use
of current medicines and developing
next-generation medicines to support
elimination and eventual eradication.
Maximizing the impact of current
medicines both for treatment and
protection of vulnerable populations
involves developing formulations for
children and gathering data on the
tolerability of medicines in pregnant
women – the two most at-risk groups.
In addition, we are working with partners
studying the use of currently available
medicines co-developed by MMV
for Mass Drug Administration (MDA)
programmes (page 37). This strategy
has been shown to accelerate the
trajectory to elimination and eradication
by targeting the human reservoir of
malaria infection and thereby reducing
transmission.1
In line with the World Health Organization
(WHO)’s Global Technical Strategy
for Malaria 2016–2030,2 and From
Aspiration to Action3 from the UN and
the Bill & Melinda Gates Foundation,
we are focused on developing future
transformational medicines to get us
from malaria control to eradication.
Given the long-term nature of research
& development (R&D) it is important
to know the characteristics of these
medicines, as described by their Target
Product Profiles (TPPs).
The TPPs of medicines needed for
malaria eradication fall into two broad
categories: treatment and protection.
The ideal medicine for treatment would
be a Single Encounter Radical Cure and
Prophylaxis (SERCaP), effective against
resistant strains of malaria that will
help improve compliance and provide
prophylaxis for at least one month after
treatment; and for protection, a Single
Exposure Chemoprotection (SEC)1
(see Table 1) for vulnerable populations.
Ideally, both medicines would be
suitable for MDA.
Delivering a single exposure medicine
places an extraordinary demand on
a molecule in terms of the required
pharmacokinetics, potency, absolute
dose, safety, tolerability and formulation;
consequently, a trade-off must be
navigated between single- and
multiple-dose therapies, particularly
when multiple-dose regimens show
activity against current resistant
strains. Although 3 days is the longest
acceptable regimen, our goal remains
the development of a single exposure
medicine.
The development of either SERCaP or
SEC will require the combination of at
least two active molecules; MMV has
defined five Target Candidate Profiles
(TCPs) for them corresponding to the
different clinical attributes needed for
the TPPs (see key features column of
Table 1).
To identify these active molecules,
develop future medicines and support
the use of current medicines, MMV is
working extensively with its growing
network of partners that today number
over 400. In 2015, the network was
augmented by the addition of four
new Japanese drug discovery partners
through the Global Health Innovation
and Technology Fund (GHIT Fund)
and Merck Serono, with whom we are
progressing a promising antimalarial
compound, DDD498 (page 20), through
preclinical development.
1 World Health Organization. Guidelines for the treatment of malaria. Third edition. (2015): http://apps.who.int/iris/ bitstream/10665/162441/ 1/9789241549127_ eng.pdf
2 World Health Organization. Global Technical Strategy for Malaria 2016–2030, (2015): http://www.who.int/malaria/areas/global_ technical_strategy/en/
3 From Aspiration to Action – What will it take to end malaria? UN Secretary- General’s Special Envoy for Health in Agenda 2030 and for Malaria, the Bill & Melinda Gates Foundation (2015): http://endmalaria2040.org/
Liver schizonts
TPP and attributes Key features TCP and lifecycle stage
Chemoprevention
The SERCaP (Single Exposure Radical Cure
and Prophylaxis)
D Single dose
D Single exposure
D Radical cure
D Targeting all lifecycle stages
D Treating all five species to infect humans
D High barrier to resistance
The SEC (Single Exposure Chemoprotection)
D Single exposure
D Suitable for mass administration at frequent intervals
D Chemoprevention for all five species to infect humans
D Orthogonal mechanism of action
Treatm
ent
Pre
venti
on
Asexual blood-stage activity
Fast clearance
Long duration of action/post treatment prophylaxis
Liver-stage activity/relapse prevention
Transmission reduction(gametocytocidal or sporontocidal)
Blood stage
Blood stage
Schizonts/Hypnozoites
Gametocytes
Table 1: Attributes of Target Product Profiles and Target Candidate Profiles for eradication
9
MMV-supported projects – 4th quarter 2015
ESAC Expert Scientific Advisory Committee
GSB Global Safety Board
MMV Board of Directors/Executive Committee/Financial Audit Committee
APMACAccess and Product ManagementAdvisory Committee
APAC Authorization for Phase III/Advancement Committee
Access andProduct
Management
GO
VE
RN
AN
CE
Research Translational Product developmentLead
optimizationPreclinical Human
volunteersPatient
exploratoryPatient
confirmatoryRegulatory
reviewPost
approval
Access
Miniportfolio Novartis
1 project Novartis
Miniportfolio GSK
Miniportfolio Sanofi
2 projectsGSK
OrthologueleadsSanofi
TetraoxanesLiverpool School of Trop Med/Univ. Liverpool
DHODHUniv. of Texas Southwestern/Univ. Washington/Monash Univ.
HeterocyclesUniv. Cape Town
HeterocyclesCelgene
HeterocyclesUniv. Campinas
Heterocycles Daiichi-Sankyo
Heterocycles Takeda
Heterocycles Eisai
ScreeningMerck Serono
Whole cellSt Jude/Rutgers Univ./Univ. of South Florida
DiversityorientedsynthesisBroad/Eisai
Other projects 24 projects
P218 (Biotec
Thailand)
MMV048Univ. Cape Town/ Technology Innovation Agency
DSM265(Univ. of TexasSouthwestern/Monash Univ.//Univ. ofWashington)/Takeda
Artemether- lumefantrinedispersible Novartis
Artesunate for injection Guilin
Dihydro-artemisinin- piperaquine Sigma-Tau
Pyronaridine-artesunateShin Poong
Artesunate- amodiaquine
Sanofi/DNDi
Open Source Drug DiscoveryUniv. Sydney
OZ439/PQPSanofi
Leadgeneration
Rectal artesunate Cipla/Strides/WHO-TDR
Pathogen BoxMMV
Artesunate- mefloquine
Cipla/DNDi
Tafenoquine GSK
Dihydro-artemisinin-piperaquinepaediatric Sigma-Tau
Pyronaridine-artesunatepaediatricShin Poong
KAE609 Novartis
KAF156Novartis
SP+AQ(sulfadoxine-pyrimethamine + amodiaquine)Guilin
DDD498Merck Serono/ (Univ. Dundee)
PA92(Drexel Univ./ Univ. Washington/ Genomics Institute of the Novartis Research Foundation)
MMV253(AstraZeneca)
GSK030GSK
SJ733St Jude/Eisai
DSM421(Univ. of Texas Southwestern/Monash Univ./Univ. of Washington)
GSK692GSK
AN13762Anacor
OZ439/FQSanofi
3 day treatment products – TPP1
› Artemether-lumefantrine dispersible (Coartem® Dispersible), generic by Ajanta
› Dihydroartemisinin-piperaquine (Eurartesim®)
› Dihydroartemisinin-piperaquine paediatric (Eurartesim®)
› Pyronaridine-artesunate (Pyramax®)
› Pyronaridine-artesunate paediatric (Pyramax®)
› Artesunate-amodiaquine (CoarsucamTM, ASAQ/Winthrop®) FDC generics by Ajanta,
Ipca, Guilin and co-blistered generics by Strides & Cipla
› Artesunate-mefloquine, co-blistered generic by Acino/Mepha
New compounds to contribute to SERCaP or MERCaP
(Multiple exposure radical cure prophylaxies) – TPP1
Seasonal malaria chemoprevention
› Sulfadoxine-pyrimethamine + amodiaquine (SP+AQ)
Severe malaria
› Rectal artesunate
› Artesunate for injection (Artesun®)
Relapse prevention
› Tafenoquine
The malaria community has defined two Target Product Profiles (TPPs) for medicines to make
eradication achievable: TPP1: a treatment combination that is ideally a Single Exposure Radical
cure and Prophylaxis (SERCaP) and TPP2: Single Exposure Chemoprotection (SEC).
Target Product Profiles
Brought into portfolio after approval. Collaboration with DNDi
Pending review or approval by WHO Prequalification, or by regulatory bodies
who are ICH members or observers
See Table 1 for descriptions of Target Candidate Profiles illustrated by the icons.
2 | Message of Wendy Sanhai and Wiweka Kaszubska
10
Dr Wendy Sanhai
MMV Board Member;
Associate Professor
(adj), School of Medicine,
Duke University, USA
Dr Wiweka Kaszubska
Vice President, Head of
Product Development,
MMV
2 Working with regulators to advance access to quality medicines
Quality is critical to MMV’s mandate.
We strongly believe that everyone,
rich or poor, deserves the most effective
and best tolerated treatments possible
when they are sick. Thus, we are
dedicated to developing innovative
medicines of the highest quality to
address the unmet medical needs of
vulnerable people at risk of malaria.
The best way to ensure quality is by
meeting the rigorous guidelines of
stringent regulatory authorities (SRAs),1
for example, those of the US Food
and Drug Administration (FDA), the
European Medicines Agency (EMA),
Swissmedic or the World Health
Organization (WHO)’s prequalification
programme. SRA approval or opinion
indicates a new medicine has met the
highest levels of safety and effective-
ness in the specific patient populations
in which it was studied. These interna-
tionally recognized approvals also
enable medicines to be procured and
distributed by international funding
bodies, such as the Global Fund to
Fight AIDS, Tuberculosis and Malaria.
The SRA assessment process of a new
drug application (NDA) often takes about
a year. To make the process as smooth
as possible, MMV engages proactively
with regulators early in the drug
development process. Ahead of dossier
submission, we ensure compliance
with the clinical data requirements and
incorporate regulatory guidance into
the design of our protocols and trials.
This decreases the risk of the dossier
failing to meet the SRA’s standard and
makes the process more efficient. In
addition, this collaborative relationship
with regulators, as well as with our
development partners, allows MMV to
leverage drug development experience
and know-how towards the ultimate
goal of benefiting patients.
SRAs are keenly aware of the need for
expedited development of drugs for
neglected tropical diseases and malaria.
In 2012, under its Food and Drug
Administration Safety and Innovation
Act,2 the FDA started the newest of
four expedited review and development
mechanisms for drug development:3
Breakthrough Therapy Designation.4
MMV/GlaxoSmithKline (GSK) received
this designation in 2013 for tafenoquine
(pages 22-23). Consequently, we have
had a number of consultations with the
FDA during the phase IIb and III studies
for tafenoquine and expect that the
application will undergo an expedited
review. The benefit of regular, real-time
feedback translates to shorter drug
development timelines which ultimately,
for patients, means earlier access to life-
saving therapies. To prepare the ground,
MMV has also begun working closely
with regulators in malaria-endemic
countries to make the drug available as
quickly as possible.
To make the process
as smooth as possible,
MMV engages
proactively with
regulators early in the
drug development
process.”
“
11
The EMA is also engaged in activities
to support approval of medicines
for neglected diseases. Since 2004,
in cooperation with WHO, the EMA
has been undertaking regulatory
assessments and providing scientific
opinion on products not intended for
use in Europe through the Article 58
procedure. Pyramax® (pyronaridine-
artesunate), developed by MMV and
Shin Poong, was the first antimalarial to
be granted a positive scientific opinion
by the EMA under Article 58 in 2012
(pages 32-33). In 2015, we were
invited by the EMA to review whether
other drugs in development might be
appropriate for the Article 58 procedure.
We took the opportunity to provide
insights gleaned from discussions with
endemic country regulators on how
Article 58 could be used to expedite
regional approvals.
Beyond the regulatory engagement
on individual drug development
programmes, MMV is representing the
wider global health community and
putting the challenges of antimalarial
drug development even higher on the
FDA’s radar screen. In 2015, we held
an MMV pipeline overview meeting at
the FDA where some of the challenges
were outlined. MMV also proposed a
scientific workshop – bringing together
global experts to discuss challenges
in antimalarial drug development.
The FDA will be hosting this event on
30 June 2016 to identify and bridge
clinical and scientific gaps in antimalarial
drug development, and inform future
regulatory decisions.
MMV also works closely with partners
to ensure their medicines meet the
criteria for inclusion in the WHO list of
prequalified medicines. We consider
WHO prequalification the seal of approval
for medicines already listed on the WHO
treatment guidelines. Recently, after
working with WHO-TDR 5 on transferring
comparative reference data, MMV has
supported two pharma partners in
their pursuit of prequalification of rectal
artesunate suppositories as a pre-
referral intervention for severe malaria
(page 36).
MMV’s goal is crystal clear: to develop
high-quality antimalarials and ensure
their timely access to vulnerable
populations. By interacting with
regulatory bodies at each stage of
development, and meeting their rigorous
standards, we are working to realize this
goal for malaria patients all around the
world.
1 A regulatory body which is: (a) a member of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) as specified on www.ich.org; or (b) an ICH observer, being the European Free Trade Association (EFTA), as represented by Swissmedic and Health Canada (as may be updated from time to time); or (c) a regulatory authority associated with an ICH member through a legally-binding, mutual recognition agreement currently including Australia, Iceland, Liechtenstein and Norway (http://apps.who.int/prequal/)
2 The Food and Drug Administration Safety and Innovation Act, Public Law 112–144, 112th Congress (2012): https://www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf/PLAW-112publ144.pdf
3 The FDA’s Four Expedited Review Pathways for Drugs: http://www.fda.gov/forpatients/approvals/fast/ucm20041766.htm
4 The FDA’s Breakthrough Therapy Designation: http://www.fda.gov/ForPatients/Approvals/Fast/ucm405397.htm
5 WHO-TDR: World Health Organization Special Programme for Research and Training in Tropical Diseases.
MMV’s goal is crystal
clear: to develop high-
quality antimalarials
and ensure their timely
access to vulnerable
populations.”
“
3 | Developing next-generation medicines
12
Addressing resistance and improving compliance
3 Developing next-generation medicines
To stem the emergence of drug resistance and reduce its impact, the World Health Organization (WHO)
recommends the use of a combination of two drugs that act in different ways. Recent reports from south-
east Asia and along India’s borders1 of parasite strains resistant to both artemisinin and partner drugs, such as
mefloquine and piperaquine, are thus of great concern.2 Populations of drug-resistant parasites can lead to an overall
reduction in efficacy and treatment failure.3 In the worst case this could lead to an epidemic of drug-resistant malaria.
Without new and effective treatment at hand, we may then start to see a rise in the malaria burden and mortality.
Current artemisinin-based combination therapy (ACT) must be taken once or twice daily over a period of 3 days. Several
studies suggest that patients often do not complete the full course of treatment, which can lead to incomplete cure and
the appearance of drug-resistant pathogens.4
MMV and partners have prioritized the development of new therapies (see Table 2) aiming to solve the challenges of drug
resistance and treatment adherence by identifying molecules with novel mechanisms of action and activity against all-
known resistant parasite strains. The new molecules either kill the parasite quickly, stay in the blood long enough to ensure
complete parasite clearance, and/or can protect against subsequent re-infection. These compounds could form part of a
Single Exposure Radical Cure (SERC) – a single-dose combination expected to ensure better compliance.
The longer-term aim is to develop a Single Exposure Radical Cure and Prophylaxis (SERCaP) that would provide some
form of additional chemoprotection and be suitable for use in mass drug administration programmes. A Multiple Exposure
Radical Cure (MERC)/MERCaP that demonstrates efficacy against key resistant strains may also be considered.
To bring you the latest on these projects, we spoke to key individuals representing MMV and its partners for their unique
insights into the development of next-generation antimalarial medicines for the treatment and prevention of uncomplicated
malaria.
Artemisinin resistance in south-east Asia is increasing
and has the potential to spread to other malaria-endemic
regions. Recently, parasite strains with resistance to the
artemisinin partner drugs have also been reported, which
could lead to loss of treatment efficacy unless alternative
compounds are identified.
In addition, current treatments must be taken over 3 days
and studies suggest that patient adherence is low. This
can lead to incomplete cure and the spread of resistant
pathogen strains.
MMV is identifying new, fast-acting compounds active
against all-known resistant parasite strains. Ultimately,
these compounds will form part of a Single Exposure
Radical Cure and Prophylaxis (SERCaP) treatment to
increase patient compliance, potentially support mass
drug administration campaigns for elimination and
combat the threat of drug resistance.
ISSUE ACTION BY MMV AND PARTNERS
1 Tun KM et al. “Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker.” Lancet Infect Dis. 15;415-21 (2015).
2 Yeka A et al. “Efficacy and safety of fixed dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children.” PLoS One. 1;9(12);e113311 (2014).
3 Phyo AP et al. “Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study.” Lancet. 379:1960-6 (2012).
4 Bruxvoort K et al. “How patients take malaria treatment: a systematic review of the literature on adherence to antimalarial drugs.” PLoS One. 9(1):e84555 (2014).
13
Tafeno-
quine
Arte-
fenomel
(OZ439)
KAE609 KAF156 DSM265 MMV048 SJ733 P218 DDD498
Target
indication
Single-dose
treatment for
relapsing
P. vivax
malaria
Part of a
single expo-
sure radical
cure
Part of a
single expo-
sure radical
cure
Part of a
single expo-
sure radical
cure
Part of a
single expo-
sure radical
cure
Part of a
single expo-
sure radical
cure
Part of a
single expo-
sure radical
cure
Potential for
seasonal
malaria
chemopro-
tection
Part of a
single expo-
sure treat-
ment of un-
complicated
malaria
Partner GSK Sanofi
(Monash
Univ./Univ.
of Nebraska/
Swiss TPH)
Novartis
(Swiss TPH)
Novartis
(Swiss TPH)
NIH/Takeda
(Univ. of
Texas South-
western/
Univ. of
Washington/
Monash
Univ.)
UCT/TIA St Jude/Eisai
(Rutgers/
NIH)
(BIOTEC
Thailand)
Merck (Univ.
of Dundee,
UK)
Stage of
development
Patient con-
firmatory
(phase III)
Patient ex-
ploratory
(phase IIb)
Patient ex-
ploratory
(phase IIa)
Patient ex-
ploratory
(phase IIb)
Patient ex-
ploratory
(phase IIa)
Human
volunteers
Preclinical Preclinical Preclinical
MMV Project
Leader
Dr Wiweka
Kaszubska
Dr Marc
Adamy
Dr Marc
Adamy
Dr Marc
Adamy
Dr Thomas
Rückle
Dr Cristina
Donini
Dr Lidiya
Bebrevska
Dr Emilie
Rossignol
Dr Lidiya
Bebrevska
Fast
parasite
clearance
Long
duration of
action
Potential
to block
transmission
Potential
to prevent
relapse
Potential
for chemo-
protection
Table 2: Activity of MMV-supported molecules in development, 2015
14
Mom Neth, from Oslev village in
Cambodia, is 20 years old and a recently
qualified VMW or Volunteer Malaria
Worker. Each day she goes to the
homes of people suspected of having
malaria. She conducts blood tests and, if
needed, administers medicines. She also
educates people about malaria and how
to use bed nets properly.
Her job is critical in this part of Cambodia,
close to the Thai border. The area has
been the epicentre of malaria drug
resistance on more than one occasion;
first to chloroquine during the first global
malaria eradication campaign in the
1950s and 1960s and, more recently,
to artemisinin and its partner drugs – the
current standard of care.
Malaria has a big impact on the commu-
nity in Oslev village – patients fall ill time and
again as the parasite develops resistance
to each medicine used to treat it.
“When someone gets malaria, they can’t
earn any money to support their family,”
Mom explains. Today, some patients in the
village are taking longer to get better after
artemisinin-based combination therapy
(ACT) than they used to. “After 3 days of
treatment, some patients still feel weak
and continue to have fevers,” Mom
continues.
It is clear that the malaria parasite is
growing resistant to the drugs being
used against it. As some ACTs are taking
longer to cure Mom’s patients she often
needs to give them alternative ACTs.
Mom and other health-care workers in
the region are concerned that the day
may soon come when all ACTs stop
working altogether and they will have
nothing left to treat their patients. We
have to be prepared for that day, with
treatments developed from new chemical
compounds that are effective against
resistant strains and easier to take. It’s the
only way to ensure Mom’s patients and
others suffering from malaria around the
world can continue to be cured from this
deadly disease.
Mom’s story
CAMBODIA
…the day may
soon come
when all ACTs
stop working
altogether…”
“
+
15
Working with partners in
Cambodia and the USA, MMV
is profiling the activity of new and in-
development molecules against drug-
resistant parasites. This information is
helping to determine which molecules
to prioritize in the development of next-
generation medicines active against all
resistant parasites.
Dr Didier Ménard and Dr Benoit
Witkowski from the Malaria Molecular
Epidemiology Unit, Institut Pasteur in
Cambodia have developed an in vitro
assay to enable testing of molecules
against the most multidrug-resistant
parasite strains we know of today
(resistant to artemisinin and partner
drugs). The assay closely emulates the
conditions the parasite experiences
in patients, and the parasite strains
come from recent clinical isolates from
Cambodian patients. This makes the
assay as representative of a real-world
situation as possible. So far, the team
have analysed around 15 compounds
from MMV’s portfolio.
Prof. David Fidock, Columbia University
Medical Center, New York, is defining
the resistance liabilities of MMV-
supported antimalarials using in vitro
culture and drug pressure methods.
These experiments provide insights into
the minimum number of parasites and
time required for resistance to emerge
as well as the degree of resistance.
Since 2011, the Fidock group have
determined the resistance profile of 44
compounds from MMV’s portfolio.
In the future, once a sufficient number of
these compounds have been trialled in
patients, we will also be able to build
a data set, which can then be used
to help extrapolate, based on in
vitro findings, how new compounds
will fare in the field. This will enable
stronger decision-making around which
compounds to develop to counter drug
resistance.
Determining activity of new compounds against resistant parasites
This molecule belongs to a novel class of antimalarial molecules, the imidazolopiperazines. It has recently completed phase IIa studies in
patients in Thailand where it was shown to be highly effective, with rapid clearance of both P. falciparum and P. vivax parasites. Over the
next year, Novartis will start a phase IIb study of KAF156 drug combinations in adults and children, with scientific and financial support from MMV.
The study will explore both the potential for a single-dose cure, and the potential for a multiday regimen to address the multidrug resistance that
has emerged in south-east Asia.
KAF156 is the result of a Wellcome Trust, MMV and Singapore Economic Development Board-supported joint research programme with the
Genomics Institute of the Novartis Research Foundation, the Novartis Institute for Tropical Diseases, the Netherlands Primate Research Centre
and the Swiss Tropical and Public Health Institute.
KAF156
3 | Developing next-generation medicines
16
What is exciting about
artefenomel as a future
antimalarial?
Usually antimalarial combinations are
developed in adults and then later,
potentially, in children. Artefenomel is
the first antimalarial to be developed
for children and adult populations in
parallel, with the goal of accelerating
access to the main target population,
African children below 5 years of age. If
we can develop a suitable artefenomel
plus partner drug formulation and if
it is confirmed efficacious against all
P. falciparum infections (including those
resistant to the major antimalarial drugs
currently used in the field) it could be
a new ‘gold standard’, that is more
convenient to take and therefore easier
to adhere to. Although an ambitious
goal, I am confident we will be able to
improve on the current 3-day treatment
regimens, with the aim of developing
the combination as a single-dose cure.
In 2015, artefenomel
was in phase IIb trials in
combination with partner
drugs, piperaquine (PQP)
and ferroquine (FQ). What
have we learnt so far and
what are the next steps?
The artefenomel+PQP trial is now
complete – 448 patients from
eight countries participated in the
trial which took 17 months from
first patient dosed to top-
line results. This was
the first-ever Single
Exposure Radical
C u r e ( S E R C )
p r o g r a m m e
we have
conducted
for malaria and provided a wealth
of information. The upper dose of
piperaquine tested was selected based
on its safety profile; however, it did not
reach a satisfactory efficacy level as part
of the combination with artefenomel.
Importantly, we were able to determine
that a dose of 800 mg artefenomel was
well tolerated.
We are now focusing our efforts on the
development of the artefenomel+FQ
combination and have transferred key
methodological learnings from the
artefenomel+PQP trial. These learnings
relate to the selected drug doses
that may be tested in young children,
the importance of Directly Observed
Treatment, and how to optimize patient
recruitment. The artefenomel+FQ
phase IIb trial started in July 2015 and
we expect the results in 2018. As part
of the clinical programme, we will also
be looking at artefenomel’s activity in
patients infected with emerging drug-
resistant strains of the parasite.
Meanwhile, we are investigating
alternative partner drugs that, in
combination with artefenomel, could
meet the requirements of the SERC
Target Product Profile.
Artefenomel, a novel trioxolane, is a lead candidate for inclusion in a new antimalarial combination with a simpler dosing regimen, specifically
formulated for children. Achieving an equivalent efficacy and safety profile in fewer doses than current 3-day ACT regimens is a major
challenge. In partnership with Sanofi, MMV is aiming to overcome that challenge and is conducting a phase IIb trial of artefenomel in combination
with ferroquine.
Q.
Q.Dr Marc Adamy
Artefenomel
Project Leader
at MMV
Dr Marc Adamy describes the potential of this compound, its current status and future plans.
Maurosia and Jemima’s story
Artefenomel (OZ439)
+
UGANDA
Maurosia Nambooze is a farmer and
the mother of 3-year-old Jemima
pictured here. Together with Maurosia’s
husband and elder son, they live in
Kafumu, Uganda, close to the banks of
Lake Victoria in the world’s most fertile
breeding ground for malaria mosquitos.
17
Robert Arch
Senior Director,
Takeda
What is special about
DSM265 as a potential
antimalarial drug?
I find the excellent research that was
published on DSM265 in the journal
Science Translational Medecine
particularly exciting.1 A strong
partnership with industry players was
built early on, and was an important
factor in developing this successful
molecule. Even more exciting are
DSM265’s characteristics, for
example, its safety and tolerability
profile to date and its proven activity
against P. falciparum as a single-dose
monotherapy used up to 28 days.
These characteristics could make
a huge difference to the lives of
populations suffering from malaria.
In 2015, DSM265
successfully completed
a phase IIa study in Peru.
What did the study teach
us about the molecule?
What challenges did the
team face?
The most important element of the
study was to show the efficacy of the
molecule in real-life settings. While the
molecule was shown to be a highly
efficacious selective inhibitor of
P. falciparum-DHODH (leading to
striking single/monotherapy efficacy
against P. falciparum), we did encoun-
ter some challenges; for instance the
compound is not as potent against
P. vivax. While this is disappointing,
it will not stop us from studying the
molecule’s effects against P. falciparum.
How is the controlled
human malaria infection
(CHMI) model supporting
the development of
DSM265?
While the real-life experience of
patients has been very important, the
CHMI model (Figure 1, page 18) has
helped us to learn more about the
parasite’s response to a single dose of
DSM265. With this model, we can also
carefully monitor the start of infection
and time our intervention accordingly.
This provides greater understanding of
DSM265’s effect on different stages of
the parasite’s lifecycle, which will help
us determine whether it should be
used for treatment or prevention.
What is the strategy
moving forward?
The next stage will be the phase IIb
studies to explore single doses of
DSM265 in combination with a partner
drug. These studies will define an
appropriate combination and dose for
a phase III study.
The phase III study will then determine
if DSM265 has the potential to be a
simpler treatment than the present-
day standard of care, which requires
multiple doses over several days.
This will involve testing DSM265 and
its partner drug in a larger number of
patients in a single dose to see if it will
provide efficacious treatment as well as
the data required for approval.
We are all very excited about the
development programme. The col-
laboration between MMV, Takeda and
GHIT, as well as other partners, will be
very important to its success.
This targeted molecule inhibits a vital enzyme (dihydroorotate dehydrogenase; DHODH) in the malaria parasite essential for its survival, while
the human enzyme remains unaffected at therapeutic concentrations with a wide safety margin. In 2015, the molecule successfully de-
monstrated safety and efficacy against Plasmodium falciparum in a phase IIa trial in malaria patients in Peru. Phase III trials will be the next step
to confirm this activity specifically against P. falciparum.
1 Phillips MA et al. “A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria.” Sci Transl Med. 7(296):296ra111 (2015).
(DSM265’s)
characteristics
could make a huge
difference to the lives
of populations suffering
from malaria.”
“
Development of DSM265 by MMV is being supported by Takeda Pharmaceutical Company, Japan, with funding from the Global Health
Innovative Technology Fund (GHIT) and pro bono support from AbbVie. Robert Arch explains the molecule’s exciting potential and next steps.
When asked about how malaria is being
tackled in Kafumu, Maurosia explains that
“community health-care workers have
done a lot, because every child sleeps
under a net – they are specialized in
giving out mosquito nets.”
Yet even so malaria can slip through the
net. Jemima is recovering from a bout of
malaria; she was sick with it last year too.
Fortunately, the family lives close to a
clinic and so can access medicines when
needed. On this occasion, Maurosia was
given ACT tablets to treat Jemima.
“I grind it and put it with water and sugar.
If it’s sour she will vomit, even if it’s mixed
with water,” Maurosia said. The ACT had
to be administered twice daily for 3 days.
“Just one dose would be better,” she
continued.
A single-dose cure palatable to children
would be a major advance in antimalarial
treatment. It would mean that children
like Jemima could receive a full curative
dose in one go, ensuring their complete
recovery and guarding against the
emergence of drug resistance.
DSM265
Q.
Q.
Q.
Q.
3 | Developing next-generation medicines
18
Controlled human malaria infection (CHMI) model
Developed with Prof. James
McCarthy from QIMR Berghofer
Medical Research Institute, Queensland,
Australia, the CHMI model tests the
blood-stage activity of candidate
medicines in volunteers inoculated
with a low number of parasites in a
tightly controlled environment prior to
receiving the investigational drug. The
model allows us to quickly understand
whether a compound will be efficacious
in humans and provides guidance on
dose selection for subsequent studies.
The model has now been adapted to
look at other scenarios such as how
molecules work in combination. In 2015,
we looked at artefenomel in combination
with DSM265. This type of study
informs the selection of partner drugs
and their doses for further development.
Based on the encouraging results of the
artefenomel and DSM265 study, a pilot
phase II combination study in patients
is planned.
In the same study to assess blood-stage
activity we can also look at transmission-
blocking capability, as shown in the
graphic above. After gametocytes
(the sexual form of the parasite) have
developed, mosquitoes are fed on the
infected blood. Then, after 10–14 days,
the number of parasites that develop
in the mosquito midgut (which could
be transmitted to another person) can
be counted. Comparison to controls
(blood samples taken prior to treatment)
allows us to determine whether the drug
candidate has transmission-blocking
potential. We are currently conducting a
pilot study with artefenomel.
One cohort of 8 volunteersper dose
One cohort of 8 volunteersper dose
Sexual parasitaemia
Clearanceof asexual parasitaemia
End ofstudy
Mosquito feeds(direct and indirect)
Rescue drug administered, if needed
Rescue drug administered
at the end
Administer drugcandidate
Inoculateparasites
D22+
10-14 D D28~D7D0
Se ual exupa asitaemmmimiimiiaaaaaaaiara ae
CCClearancelle anof ase ual f a exuparasitaemiamiaar ita
Mos(direc*
Monitor parasitaemia in volunteers*
Count parasitesin the mosquito
dd
Figure 1:
19
Developing new drugs for use in
pregnant women is extremely
challenging. Pregnant women are
excluded from trials of new drugs until
the risks and benefits are well under-
stood among non-pregnant adults,
yet drug dosing can differ between
these groups. Current WHO guidelines
allow for the use of artemisinin-
based combination therapies (ACTs) for
women with malaria in the second and
third trimester of pregnancy, but not
for the first trimester when the fetus is
most vulnerable, as there is an absence
of key safety data. Additionally, in the
absence of suitable alternatives some
malaria experts suggest that ACTs
could also be used as chemoprevention
in pregnancy, which could lead to the
problematic situation of the same
medicines being recommended
for both chemoprevention
and treatment.
New antimalarial medicines that are
well-tolerated in pregnancy are needed
for both treatment and protection. While
we cannot definitively predict which
medicines will be suitable in pregnancy,
we can identify early on which medicines
would not be. Traditionally, preclinical
studies to determine if a molecule
has a safety signal are conducted in
parallel with phase II studies. MMV
has developed a strategy to move
this testing forward so it is in parallel
with the first-in-human
studies in phase I.
This was successfully carried out for
the last two development candidates,
MMV048 and DSM265. We now
propose taking this one stage further
and making safety in pregnancy one
of the first safety tests performed in
preclinical evaluation. In this way, we
will ensure that medicines to protect
vulnerable populations are identified
as early as possible and prioritized for
further development.
Prioritizing molecules for pregnant women
3 | Developing next-generation medicines
DDD498
Dr Beatrice Greco
Head of the
Malaria &
Diagnostics
Innovation
Cluster, Global
Health Research
& Development
at Merck S.A.
(Switzerland)
a subsidiary
of Merck KGaA
What is exciting about
DDD498?
DDD498 has a novel mechanism
of action: in preclinical models, it
has shown activity against parasites
resistant to currently available
antimalarials, and indications of high
potency. Owing to these attributes,
it has potential to become a highly
efficacious compound and to play
an important part in the treatment of
uncomplicated malaria in the future.
Due to its predicted long half-life,
it might have potential to protect
against malaria in endemic countries
(chemoprotection), and as it inhibits
gametocyte formation, it might also
block transmission, which would be
essential for eliminating malaria. All of
this is a promising premise for further
investigations.
What are the next steps for
the project?
In February 2016, based on the high
quality of the molecule and the data on
its biological activity, the decision was
taken to progress the compound into
the regulatory preclinical phase of drug
development.
The team is currently completing the
essential preclinical and regulatory
activities required to determine if
DDD498 can then enter into first-in-
human trials potentially in 2017. This
includes pivotal toxicology studies as
well as in vitro and in vivo studies of drug
metabolism and pharmacokinetics.
The data generated will enable us to
determine if future clinical development
is possible and what a safe starting
dose and regimen would be, as well as
the predicted therapeutic range for the
clinical trial.
We look forward to continuing the
excellent collaboration with the very
committed and supportive team at
MMV.
2015 was a big year for DDD498. Not only was the team at the University of Dundee selected to win MMV’s Project of the Year 2014
for its discovery and the details of the compound published in Nature,1 but MMV also signed a contract with Merck KGaA, Darmstadt,
Germany, to continue its future development.
Dr Beatrice Greco explains what’s exciting about the molecule as well as the next steps.
Q. Q.
20
1 Baragaña B et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 522(7556):315-20 (2015).
Getting the formulation right
Dr Elizabeth Vadas
InSciTech Inc.,
Canada
What formulation
challenges do drug
developers face?
Poor solubility, low permeability and,
in particular, lack of potency represent
significant formulation challenges.
For example, the formulation of low
potency drugs, requiring high doses,
is technically complex, especially in
the field of malaria where we deal with
combination drugs – two different
molecules in one capsule or tablet. If,
for example, the dose of one or both
drugs is high, the tablet may become
too large to swallow. We must then
divide the dose into several smaller
tablets.
Are there any other
challenges particular to
malaria drug development?
Yes, since the target population for
malaria drugs is mainly sick children,
we must formulate for them. Specific
considerations for children include
dosage form, ease of administration
and palatability – bearing in mind the
patient is likely to already be nauseous.
Working with drug combinations
complicates formulation further as the
two active entities must be chemically
compatible; if not, we need to come up
with formulation approaches that can
separate the two active ingredients in
one dosage form. This can be a high
technical hurdle. The stability of the
dosage form in hot and humid countries
represents an additional challenge.
Ideally, we would like to achieve all this
in a single-dose cure – a goal which
increases the scientific and technical
complexity both for the drug molecule
and the formulation.
What motivates you to work
with MMV on a pro bono
basis and how have you
helped the project teams
to overcome formulation
challenges?
I have had a wonderful, productive
career in the pharmaceutical industry,
and now that I am retired I feel it is
time to give something back. I hope
that I have been able to advise the
MMV teams on potency, form selection
and other formulation requirements
before molecules enter phase I trials.
Together, we have been able to find
promising formulation approaches
for MMV048 and DSM265. The more
issues we solve at the beginning of
drug development the more likely we
are to succeed.
It is critical to get the formulation of a new drug right to ensure it is easy to administer and store, acceptable to the target patient
population, delivers the correct dosage, and has the desired effect when administered. To do so, it is important to select the correct
chemical and physical forms of a drug at an early stage in development, as formulation changes can be very costly, create delays and
result in poor quality clinical data that is difficult to interpret.
Dr Elizabeth Vadas describes the challenges of drug formulation and explains how and why she has been assisting the project teams
at MMV.
Q. Q. Q.
21
3 | Developing next-generation medicines
22
Aiming to stop relapsing malaria with a single- dose treatment
The Plasmodium vivax malaria parasite has the ability to
lie dormant in the liver as hypnozoites, which periodically
reactivate leading to a relapse of malaria in the absence
of a new infective mosquito bite. It is estimated to cause
around 70–80 million clinical infections every year.1
Primaquine is currently the only treatment available to kill
the dormant parasites and stop the relapse. It must be
taken once a day for 7–14 days.
MMV and GlaxoSmithKline (GSK) are developing
tafenoquine, as a potential single exposure medicine to
prevent P. vivax relapse by addressing the hypnozoite in
the liver.
ISSUE ACTION BY MMV AND PARTNERS
1 Mendis K et al. “The neglected burden of Plasmodium vivax malaria.” Am J Trop Med Hyg. 64 (1–2 Suppl): 97–106 (2001).
Pring’s storyPring Chon is a soya bean and cassava farmer
from Oslev Village, Cambodia, where he lives with
his wife and children. He has suffered with malaria
more than 12 times in his life; on one occasion it
led to severe malaria and he had to be hospitalized.
Pring has been infected with P. vivax malaria that
lies dormant in the liver only to relapse periodically,
without warning and in the absence of a new
infective mosquito bite.
“I feel bad with this illness,” Pring explained. “When
I’m infected, I can’t work and my wife can’t work.”
This debilitating disease affects Pring regularly. In
Cambodia, artemisinin-based combination therapies
(ACTs) are used to treat blood-stage malaria
infections, leading to quick relief of symptoms;
but there are no medicines routinely used in the
country to cure malaria relapses. Without treatments
aimed at eliminating the dormant liver parasite they
continue to suffer.
CAMBODIA
When I’m
infected, I can’t
work and my
wife can’t work.”
“
+
23
Tafenoquine is an investigational medicine in phase III development. If approved, it would be the first new medicine to cure relapsing malaria
in over 60 years. Tafenoquine is being developed as a single dose to prevent malaria relapse, to be administered alongside a standard
3-day ACT to cure the immediate infection.
Tafenoquine is a member of the same chemical family as primaquine; both are associated with a risk of haemolytic side-effects in patients
lacking the enzyme glucose-6-phosphate dehydrogenase (G6PD). GSK is working with PATH to accelerate the development of a G6PD point-
of-care diagnostic test, so that patients’ G6PD status can be tested to determine if tafenoquine or primaquine can be safely administered.
What is exciting about
tafenoquine as a future
antimalarial?
WK: Tafenoquine is a game-changer in
many ways; if approved by regulators,
it will be the first medicine indicated for
relapse prevention of P. vivax malaria
since the 1950s. It is the only tool in
the malaria pipeline for the elimination
and eradication of P. vivax malaria
that acts on the ‘hidden reservoir’ of
parasites in the liver. Furthermore, to
improve patient compliance we are
developing tafenoquine as a single-
dose treatment that could potentially
transform the treatment approach for
relapsing malaria.
How is the phase III
programme progressing?
JPK: Tafenoquine has been in phase III
clinical development since April 2014
in eight P. vivax malaria-endemic
countries investigating a single dose of
300 mg; this dose was selected based
on results of phase II dose-ranging
studies. We expect to finish recruitment
for the phase III programme in 2016.
What are the implications
of the US FDA designation
of Breakthrough Therapy
and how is engagement
with other international
regulatory authorities
progressing?
JPK: The Breakthrough Therapy
Designation was enacted as part of
the 2012 FDA Safety and Innovation
Act (FDASIA). The goal is to expedite
the development and regulatory review
of designated drugs to treat serious
or life-threatening medical conditions
when the drug may offer substantial
improvement over available therapies.
Additionally, this designation affords us
more intensive guidance from the FDA
on tafenoquine’s clinical development
plan. Stringent regulatory review of
a tafenoquine dossier by the FDA
would precede planned subsequent
registrations in malaria-endemic
countries.
How is the patient access
plan progressing and
how is each partner
contributing?
WK: MMV is working with GSK, PATH
and other groups to develop the access
plan well in advance. The partners
meet quarterly to make sure the plans
are aligned and will be delivered in
concert. GSK has been in a partnership
with us for a number of years and is
responsible for the overwhelming
majority of the drug development work;
MMV has supported GSK strategically,
tactically and financially. The Bill &
Melinda Gates Foundation, in addition
to sponsoring the new diagnostic test,
provides regulatory and patient access
expertise through their contacts in the
field.
How is the G6PD point-
of-care test progressing in
partnership with PATH?
JPK: The potential benefit of using a
new medicine versus the associated
risks of haemolytic side-effects is at the
forefront of our minds. The goal of the
PATH/GSK collaboration is to have at
least one diagnostic test suitable for
use with tafenoquine at the time of its
potential approval. We are currently
working with two diagnostic companies
to develop their differing technologies
and to assess the ability of each to fulfil
the specification that we believe would
be required.
We asked Dr Wiweka Kaszubska and Dr JP Kleim to provide an update on the phase III programme. They also explain the advantages of
having obtained a ‘Breakthrough Therapy’ regulatory designation from the US Food and Drug Administration (FDA) and discuss how they
are collaborating with other partners to ensure access to the medicine.
Dr Wiweka
Kaszubska
Vice President,
Head of Product
Development,
MMV
Dr JP Kleim
Project Leader,
GlaxoSmithKline
UK
Q.
Q.
Q. Q.
Q.
Tafenoquine
4 | Advancing the science of eradication
24
Candidates delivered in 2015
4 Advancing the science of eradication
To identify molecules that meet the
Target Candidate Profiles (TCPs)
(page 8) for next-generation medicines
to support malaria eradication, MMV’s
drug discovery team works with partners
to screen compounds for activity against
the various stages of the parasite lifecycle
(Figure 2).
To complement existing blood-stage
assays, (which identify compounds
to alleviate the symptoms of malaria),
MMV and partners have developed
new assays to screen for activity at
other lifecycle stages. Notably, in 2014
and 2015, high-throughput assays of
liver stages (to test for chemoprotection
capability) and gametocyte stages (to
test for transmission-blocking capability)
as well as assays of Plasmodium vivax
liver stages (to test for anti-relapse
activity) were established (pages 28-29).
Active compounds that meet the
required criteria are then progressed to
the ‘make–test’ cycle (Figure 2). Here
they undergo rounds of synthesis and
testing to determine whether they could
become a drug candidate, suitable for
further development.
Since 2010, 17 drug candidates
have been brought into preclinical
development (13 are still active). Each
one of these active candidates has
the potential to form part of a next-
generation medicine to support malaria
eradication.
MMV drug discovery by numbers
44 pharmaceutical and academic partners
7 million compounds screened against the blood stages of Plasmodium falciparum
25,000 chemical starting points identified
19 assays developed or in development against the critical stages of the parasite lifecycle
17 drug candidates brought forward since 2010
DSM421 Preclinical
Target indication:
Part of a single exposure radical cure and
potential for chemoprophylaxis
TCPs: Asexual blood-stage activity and
chemoprevention
Features:
• Favourable physicochemical properties
• Comparable ex-vivo activity on
P. falciparum and P. vivaxMMV Project Director: Dr Emilie Rossignol
GSK692 Preclinical
Target indication:
Part of a single exposure radical cure and
potential for chemoprophylaxis
TCPs: Asexual blood-stage activity
Features:
• Predicted human dose < 500 mg
• Favourable physicochemical properties
• Extremely rapid parasite clearance
• Inability to select resistant mutants
MMV Project Director: Dr Jörg Möhrle
Partner: GSK
AN13762 Preclinical
Target indication:
Part of a single exposure radical cure and
potential for chemoprophylaxis
TCPs: Asexual blood-stage activity,
transmission-blocking activity and chemo-
prevention
Features:
• Reduced human dose < 50 mg
• Favourable physicochemical properties
• Rapid parasite clearance
• Potential for prophylaxis
MMV Project Director: Dr Cristina Donini
Partner: Anacor
25
Does
the
co
mpound have activity against malaria?
Does it have:
17 new candidates 2010–2016
Activity against the blood stages, liver stages and/or transmission stages of the parasite?
Novel chemistry?
Desirable mechanism of action?
Attractive drug-like properties?
Does it have:Acceptable pharmacokinetics, efficacy and safety?
Developability?
An acceptable predicted dose?
4. Re
sults
2. Synthes
is
1. Hypothesis
3. Test
Make-test
cycle
Translational step
Parasitelifecycle
MMV’s drug discovery engine
Figure 2:
4 | Advancing the science of eradication
26
Research can be
conducted with varying
degrees of openness, as
described in the margin.
How would you define
MMV’s approach to drug
discovery?
MMV’s approach is Open Innovation.
At one end you have the ‘cathedral
approach’ that is secret and siloed, at
the other end everything is laid bare –
information, compounds and biological
tools. MMV’s approach lies between
the two. Over the years we have built
up a community that shares data and
assays among a set (or subsets) of
partners for a given project or projects.
These Open Innovation projects are
not transparent to the outside world,
rather they operate within contractual
‘bubbles’, with a semi-permeable
membrane securing confidentiality.
What are the advantages of
this approach?
Risk, cost and effort are shared among
the partners. We delude ourselves if
we think we are the best and only we
can deliver. Through collaboration we
can do so much more than we can
alone. Since 2010, our collaborations
have delivered 17 candidate molecules
for malaria – this has created a strong
pipeline, but it’s still not strong enough
to deliver the medicines we need to
defeat malaria. To achieve our mission,
we continue to enlarge our partnership
network and in turn the quality of
compounds in the pipeline.
The confidentiality membrane allows
for the key partner to generate
intellectual property and file a patent.
This potential can be a strong incentive
for pharmaceutical partners to get
involved, as well as allowing us and our
partners to help guarantee the quality of
the clinical trials and final product. New
partners have access to all the valuable
assays and expertise available, which
helps minimize duplication.
Are there any challenges?
Open innovation can only function
with an extremely competent business
development and legal group.
They need to be extremely flexible
to induce partners to join but also
sufficiently uncompromising, in terms
of accountability and alignment with
MMV’s mission, to develop affordable
medicines for vulnerable populations.
At MMV we are fortunate to have that.
Also, as we rely on donor funds we
set annual budgets which means if a
project doesn’t make the grade we
must be ruthless and terminate it.
In response to various challenges,
variations of the open model are being
tried and tested. In one example,
working with Dr Mat Todd at the
University of Sydney in Australia, we
have completely broken the membrane
and made everything open.
How does this open source
initiative work and what
have you learnt so far?
Essentially, everything related to the
project is in the public domain, such
that anyone anywhere can follow and
contribute. The idea is that it will work
by ‘natural selection’ – anyone can
take what’s there and over time there
will be evolution, in this case, delivery.
We have learnt that there is a huge
amount of goodwill and so intellectual
input, but fundamentally money and
resources are still rate limiting. If people
don’t make compounds you get stuck.
We believe in open source – but it
needs to be resourced. Intention is
also critical. You need to be clear on
what you are setting out to achieve and
direct the project accordingly.
Opening up malaria drug discovery
Open Science:
Deposition of
data in the public
domain.
Open Access:
Data, compounds,
publications etc.
made available
to maximize their
possible use
across diseases.
Open
Innovation:
Two or more
partners share
data within a
‘walled garden’
with the intention
to deliver a
product.
Open Source:
All project data
and structures are
laid bare and the
wider community
is invited to fully
engage and offer
support e.g.
advice, synthesis,
testing and in-
kind technology.
To drive the elimination and eradication of malaria,
there is an urgent need for novel compounds,
active against the various stages of the malaria
parasite lifecycle, to be discovered and developed.
To make the discovery and progression of
exciting compounds more efficient, rapid and
cost effective, MMV has pioneered new, more
open and collaborative ways of working.
ISSUE ACTION BY MMV AND PARTNERS
Dr Jeremy Burrows, Vice President,
Head of Drug Discovery, MMV,
explains MMV’s open approach to
drug discovery.
Q.
Q.
Q.
Q.
27
Open access initiatives to catalyse drug discovery
Following the release into the public
domain of data on 20,000 compounds
active against malaria, there was a need
for scientists to access the physical
compounds with which to initiate drug
discovery programmes.
MMV launched the Malaria Box in 2011
and the Pathogen Box in 2015.
ISSUE ACTIONMore than 250
Malaria Boxes and
70 Pathogen Boxes
dispatched since
launch in 2011 and
2015, respectively
35 papers published
describing Malaria Box
screening results
Researchers screening
the Malaria Box found
hits against 16 different
protozoa, 7 helminths,
9 bacterial and
mycobacterial species,
the dengue fever
mosquito vector and
human cancer
cell lines
Wellcome Pathfinder
grants of USD 100,000
each awarded to
Prof. Chris Huston,
University of Vermont,
and Prof. Robin
Gasser, University
of Melbourne, for
research on Malaria
Box compounds
active against
cryptosporidiosis
and parasitic worms,
respectively
Dr Fabrice Boyom is investigating natural products for the treatment of human, animal, and/or plant
diseases. To help fuel his research he received MMV’s Open Access Malaria Box, a Malaria Box
Challenge Grant and recently the Pathogen Box. Dr Boyom explains how he and his team have
been using these resources.
What was your initial
reaction when you heard
about the Malaria Box
initiative?
Wow! This is a real opportunity to have
compounds to work on. As in other
poorer countries in the world, the
discovery of new drugs for parasitic
infections in Cameroon is hampered
by the lack of resources devoted to
drug discovery. It is not easy to purify
effective compounds from plants. It’s
a long and demanding process. The
Malaria Box provided a wonderful
opportunity to research compounds
that you know work.
How are you using the
compounds? What did your
research reveal?
The compounds are being screened
against Toxoplasma gondii and
Entamoeba histolytica, but also against
pathogenic yeasts and bacteria. As
a result, we identified seven anti-
Toxoplasma gondii hits, as well as
two moderately active compounds
against E. histolytica. Also, two
compounds showed highly potent
activity against various Candida spp.
and Cryptococcus neoformans (one
of which is the already known Crystal
violet). We are now optimizing two of
the compounds.
You have also recently
requested the Pathogen
Box. How will you use the
compounds?
The Pathogen Box is another great
opportunity to expand our research and
continue the work we are doing. We
will also screen the compounds against
Mycobacterium ulcerans (the causative
agent of Buruli ulcer) and eventually
against pathogenic yeasts such as
Cryptococcus neoformans.
It’s exciting to be involved in science to
save lives. Through these open access
initiatives and grants, we have not only
been able to continue our research but I
have also been able to train my students,
who can then continue the work in
Africa. I’m very grateful for the guidance
from MMV and I’m looking forward to
continuing this work in the future.
Q.
Q.
Q.
Dr Fabrice Boyom
Researcher at
the University
of Yaoundé 1,
Cameroon
1 Ascariasis, Buruli ulcer, Chagas disease, Cryptosporidiosis, Hookworm, Human African trypanosomiasis (sleeping sickness), Visceral & cutaneous leishmaniasis, Lymphatic filariasis, Malaria, Onchocerciasis (river blindness), Schistosomiasis, Trichuriasis and Tuberculosis.
The Open Access Malaria Box contains 400 diverse molecules, representative of the original
20,000 set and active against blood stage Plasmodium falciparum malaria. The box was made
available to researchers for free on request. Based on the success of the Malaria Box, MMV was
awarded a grant from the Bill & Melinda Gates Foundation for a follow-on project, the Pathogen
Box. This box also contains 400 molecules for distribution to scientists for free on request, but this
time with activity not just against malaria, but also against one of a range of neglected diseases.1
4 | Advancing the science of eradication
28
Historically, basic research on P. vivax has lagged behind that for Plasmodium falciparum. This is partly because P. falciparum was
considered the more deadly of the two and because P. vivax parasites were difficult to access and to work with. Even today the technical
challenge is great; the blood-stage parasites still can’t be maintained in continuous culture.
Nevertheless, the discovery and development of anti-relapse molecules has always been a key research and development (R&D) focus for MMV.
For example, over the years, investments have been made in testing new clinical candidates, developing tafenoquine with GlaxoSmithKline
(GSK) and developing new clinical models in collaboration with the Indonesian army. Up to now, the major advances in cell biology have been
made through Wellcome Trust co-funded collaborations with the Dutch Primate Centre, and Novartis-led discovery projects. Over the last year
we have seen a significant change in the assays coming through, thanks to a continued effort on the part of our collaborators, complemented
by new funding from the Bill & Melinda Gates Foundation to establish a P. vivax Malaria Consortium.
New models to discover new molecules against the relapse
The relapse of Plasmodium vivax malaria contributes
to a significant burden of disease – an estimated
70–80 million clinical infections every year. Only two anti-
relapse medicines exist (primaquine, which is available,
and tafenoquine, which is in development, pages 22-23)
and both are associated with side-effects in patients who
have a certain genetically determined enzyme (G6PD)
deficiency.
Develop and employ new models to discover new
molecules that are active against the dormant liver stage
of P. vivax malaria.
ISSUE ACTION BY MMV AND PARTNERS
How does the assay
work and what are its
advantages?
The assay allows us to see the impact
of various test compounds on small
and large liver P. vivax forms. We
culture the human liver cell line in an
8-well plate and then add P. vivax
sporozoites (the liver-infective stages
of the parasite) into each well a day
later. We then add the test compounds
to the cultures in triplicate at a range
of concentrations. Six days later, we
count the small and large parasite
forms (believed to be hypnozoites
and schizonts, respectively) take the
average and compare them with the
control wells.
Our system is in vitro and uses the
human liver cell line, which means we
can handle many more compounds
and concentrations at the same time.
As we use the same cell line, the
findings are more robust, compared
to a humanized mouse model, for
example.
We have been working with 96-well
plates, but are now moving to 384-
well plates, which will then enable us
to screen yet more compounds in one
go. With this assay, depending on the
stage at which we add the compound,
we can look at either the effect of the
compound on the development of
small and large forms (potential for
chemoprevention) or the effect on
fully developed forms (potential for
radical cure – killing of hypnozoites and
relapse prevention).
How many compounds
have you been able to
screen and what have you
found so far?
We finished screening the first
25 compounds from MMV in the
chemoprevention model and are in
the process of testing 100 more. We
have found some molecules with very
good potential. Next, we will screen the
Pathogen Box compounds (page 27).
Our goal for the year is to validate
the 96-well plate, initiate the 384-well
plate format and screen up to 1,000
compounds.
What has it been like to
work with MMV and the
Gates’ P. vivax Malaria
Consortium?
The project is managed with an
industry-style approach so the
timelines are tight which can be
challenging, but I do enjoy it. I enjoy
understanding the different research
perspectives and because the funding
is stable we can progress smoothly. If
just one molecule screened from our
system ultimately treats people it will
be a goal fulfilled.
Dr Jetsumon
Sattabongkot
Prachumsri
Head of the
Mahidol Vivax
Research Unit,
Thailand
In 2014, a team of researchers from Mahidol University, Thailand, was able to establish a P. vivax ‘hypnozoite’ cell-based in vitro assay to
screen up to 1,000 compounds a year. Dr Jetsumon Sattabongkot Prachumsri talks about the assay, what it has told us so far and what
it’s like to work with the Consortium.
Q.
Q. Q.
100x P. vivax liver stage development
in vitro day 7 post sporozoite infection
29
How is your work to
establish a P. vivax
‘hypnozoite’ cell-based
in vitro assay progressing?
It’s really exciting, we’ve had several
breakthroughs in the last couple of
years. We are now able to culture
primary human hepatocytes for
more than 4 weeks, infect them
with sporozoites and get parasite
development all the way to invading
reticulocytes.
All of this has now been achieved in a
384-well plate format with which we
can attempt high-throughput screening
for the first time. We have begun by
screening 27 of MMV’s compounds
several times to help refine the assay.
We expect to screen at least 1,000
compounds this year for MMV.
What are the advantages of
this assay?
Because we can maintain the primary
human hepatocytes in culture for
more than 4 weeks, we can routinely
do radical cure screens and assess
hypnozoite activity from days 5–9 post-
sporozoite invasion. We can also look
for relapse in vitro from as early as day 21
and as late as days 33–35.
We have found that human hepatocytes
prefer to be confined in a 3D space.
So by optimizing the ‘microfeature’
design at the bottom of each well we
can promote optimal development of
hepatocytes and the parasite. As this
is all conducted in a 384-well format
our screening is both high-content and
high-throughput.
What has it been like to
work with MMV and the
Gates’ P. vivax Malaria
Consortium?
It’s a good example of how sharing
information early can be very helpful.
It’s a high-risk project so working
individually through independent
grant systems would not have been
successful. Although, in a sense, the
groups are competitors, we routinely
share information through interactions
in the Consortium. When we have
something that does or doesn’t work,
we inform the other groups and vice
versa. It works very well – for example,
we got confirmation of what the
hypnozoite looks like in two different
in vitro models and a mouse model. It’s an
example of how the Gates’ Consortium
model can work to solve big problems.
Working with other members of the
Consortium has been critical. The
biggest challenge is getting access to
the sporozoites so that we can actually
do the assays. We are grateful for the
contributions of Jetsumon Prachumsri,
Chiara Andolini and Francois Nosten
in the field in Thailand who provide us
with infected mosquitoes.
MMV was involved right from the
beginning as advisors and contributors
to all the discussions. They are the
leader in the field of malaria drug
discovery. Being able to access all the
different compounds and test systems
in their network was invaluable in
refining and validating our assay. We
hope they can now reap the rewards
by using the models to find the next
drug to kill the hypnozoite.
Prof. Dennis Kyle
Distinguished
University Health
Professor,
University of
South Florida,
USA
In 2015, a second team of researchers was also able to establish a P. vivax ‘hypnozoite’ cell-based in vitro assay. Prof. Dennis Kyle
explains the progress, the advantages of their assay and what it’s been like working with the Consortium.
Q.
Q.
Q.
4 | Advancing the science of eradication
30
MMVProject of the Year
2015
GSK692 – a novel compound steadfast in the face of resistance
The team at GSK,
Tres Cantos, Spain
GSK692 is an antimalarial
compound with a novel mode of action
which enables it to kill the malaria
parasite quickly. Its overall properties
indicate it could form part of a single-
dose cure and it has a low propensity
to generate resistance in laboratory
studies as well as activity against current
drug-resistant strains – key attributes
for a next-generation antimalarial. In
recognition of this, the GSK692 project
team has won MMV’s 2015 Project of
the Year award and MMV’s External
Scientific Advisory Committee (ESAC)
has approved the compound as a
clinical candidate for further research.
GlaxoSmithKline (GSK) and MMV
have worked in a productive and open
collaboration on malaria drug discovery
for several years. GSK’s facility at Tres
Cantos in Spain houses one of MMV’s
centres of excellence for screening and
testing new compounds in biological
assays, transmission-blocking models
and parasite-killing studies. It is
expected that further clinical candidates
will emerge from the MMV/GSK
collaboration in the future – following in
the footsteps of GSK692.
Its fast mode of
action could make it
a suitable replacement
for artemisinin, the
current gold standard
treatment.”
“
31
What is special about
GSK692?
LS: GSK692 is special because it
combines a number of desirable
properties for an antimalarial. It targets
blood-stage activity of the Plasmodium
falciparum and Plasmodium vivax
parasites. It provides a rapid response
when tested in vivo in laboratory
models of malaria. Importantly, this
is complemented by a rapid in vitro
response. The molecule also displays
an extremely low propensity to select
for resistance in vitro, hence, we predict
a low rate of selection for resistance in
the field. Its fast mode of action could
make it a suitable replacement for
artemisinin, the current gold standard
treatment. Also, GSK692 is not
structurally related to artemisinin and
has a unique mode of action, which
is of paramount importance when
developing effective, novel combination
treatments for a disease that has a
history of developing drug resistance.
How was the compound
discovered?
LS: The molecule was identified in
collaboration with MMV through a
programme which screened the entire
GSK corporate compound collection
against malaria at Tres Cantos in
Spain in 2010. This programme led
to the identification of what we call
the ChEMBL TCAMS (Tres Cantos
Antimalarial Set). The results were
published in Nature1 in 2010 and made
publicly available to the global drug
discovery community.
The next step was to triage the active
compounds, using innovative tools
such as assays, to determine speed
of killing and transmission-blocking
potential as well as GSK’s rigorous
quality criteria. Ferrer, a pharmaceutical
company based in Barcelona, then
joined the team working with GSK
and MMV to further improve the series
until 2013 when they stopped their
malaria research activities. The joint
programme focused on improving the
molecules’ developability properties,
like solubility and physicochemical
properties. GSK692 emerged as the
best molecule.
What are the next steps for
the project?
PW: As GSK692 has now been
approved as a clinical candidate by
the ESAC, the next step is to prepare
a larger quantity of the compound for
regulatory studies, which will determine
whether it is safe to progress to clinical
trials. The plan would then be to
start a phase I clinical trial looking at
tolerability and pharmacokinetics in
human volunteers and studies in the
controlled human malaria infection
model (page 18) to explore efficacy.
What value has MMV
added to the project as a
partner?
LS: MMV provides overall guidance
based on its extensive experience in
the discovery and development of
antimalarial molecules. Specifically,
MMV has been fundamental in the
final profiling of the molecule’s activity
against the various stages of the
parasite’s lifecycle by providing access
to critical biological assays through its
established network of collaborators.
MMV’s Project Director Paul Willis
and other MMV staff members act
as consultants. Their support and
guidance has helped us overcome
the challenges that arose during the
project’s progress. The consistent
level of open communication in
this partnership has significantly
contributed to the success of the
project and the molecule’s selection as
a potential new medicine.
Why does the collaboration
between MMV and GSK
work so well? What does
GSK bring to malaria drug
discovery?
PW: There has been an excellent
collaborative atmosphere – both
sides respect and value each other’s
contributions. It means we can discuss
the science in an open and transparent
manner. In addition to the drug
discovery projects, GSK houses one
of our screening centers of excellence
at Tres Cantos. They run several key
biological assays for malaria, providing
data on efficacy, transmission-blocking
potential and the rate of killing of the
malaria parasite for all projects in the
MMV drug discovery portfolio. Their
broad malaria expertise and drug
discovery knowledge makes for a really
powerful, promising and beneficial
collaboration. To illustrate this, GSK
also had another candidate – GSK030
– approved last year and there are
several promising new projects in the
portfolio which we hope will deliver
exciting new drug candidates in the
future.
Dr Paul Willis
Director, Drug
Discovery, MMV
Dr Laura Sanz
Tres Cantos
Medicine
Development
Campus,
GlaxoSmithKline,
Spain
Dr Paul Willis and Dr Laura Sanz talk about the award, the compound and the collaboration.
1 Gamo FJ et al. “Thousands of chemical starting points for antimalarial lead identification.” Nature. 20;465(7296):305-10 (2010).
Q.
Q.Q.
Q.
Q.
5 | Getting better medicines to more people
32
Dr Borghini, you have
led the development of
Pyramax tablets and
granules on behalf of MMV
since 2006. What was
it about the project that
inspired your commitment?
IB: Initially, I was struck by the high
efficacy results demonstrated in phase II
studies. With 98% cure rates, Pyramax
showed tremendous potential.
Then I had the opportunity to go
to Burkina Faso, where I met with
doctors and malaria patients. When
you make a trip like that, you quickly
come to understand why we do the
work we do – the need is enormous. I
was impressed by the team I met and
inspired by their dedication. The project
became even more meaningful to me.
Developing treatment options for children
5 Getting better medicines to more people
Children are the hardest hit by malaria – around 70% of
those that die are under 5 years of age. Yet typically in
drug development, medicines are developed for adults
before child-friendly versions are pursued.
Developing and improving access to child-friendly
formulations of existing antimalarials for treatment
(artemisinin-based combination therapies; ACTs), and
chemoprevention (sulfadoxine-pyrimethamine; SP+AQ).
Developing next-generation medicines for children in
parallel with adult formulations.
ISSUE ACTION BY MMV AND PARTNERS
Dr Isabelle
Borghini
Director, Product
Development,
MMV
Mr Won June
Chang
CEO, Shin Poong
Pharmaceutical
Dr Isabelle Borghini and Mr Won June Chang talk about the development of
Pyramax tablets and granules and the value of the partnership.
Q.
MMV has long recognized that developing better medicines for children helps address the most vulnerable patient population at greatest
risk of dying from malaria. The first product successfully co-developed by MMV and partners was Coartem® Dispersible, launched by Novartis
in 2009. To date, 300 million treatments of this cherry-flavoured dispersible product have been distributed, making it the most widely-used
quality ACT for children.
In 2015, Pyramax® granules (pyronaridine-artesunate), developed by Shin Poong Pharmaceutical and MMV, received a positive scientific
opinion under Article 58 from the European Medicines Agency (EMA), becoming the second ACT specifically designed for paediatric use to
receive approval from a stringent regulatory authority.
A third ACT co-developed by MMV (with Sigma-Tau) was Eurartesim® (dihydroartemisinin-piperaquine). Eurartesim was approved by the EMA
in 2011 and received WHO prequalification in 2015. Its paediatric formulation has just completed clinical development and is expected to be
submitted for EMA approval in 2016.
What is special about
Pyramax?
WJC: It is the first ACT approved by
a stringent regulatory authority (SRA)
for treatment of both P. falciparum and
P. vivax malaria. This is really useful
in areas where both species cause
infections and in particular where access
to differential diagnosis is limited.
Importantly, the medicine is available
in two formulations, a tablet for adults
and children over 20 kg and specifically
formulated, taste-neutral granules for
children and infants between 5 kg and
20 kg. This child-friendly formulation
helps ensure they get the full curative
dose they need. Both formulations can
be administered with or without food
and only need to be taken once a day
for 3 days, making administration and
adherence easier than with current
twice-daily dosing regimens.
What was the biggest
challenge in the
development of the
combination and how did
you overcome it?
IB: During the phase III programme,
we conducted a phase I relative
bioavailability study in healthy
volunteers, in which we detected a
liver safety signal. We immediately
put the phase III programme on hold
and prepared a data package to be
reviewed by a panel of the world’s
top hepatic safety experts. They
scrutinized the data and made the
recommendation to continue the
programme. This was a make-or-break
moment for the Pyramax development
programme. Pyramax then went on
to receive positive scientific opinion
from the EMA in 2012 for treatment
of a single malaria episode in areas
of low transmission with evidence of
artemisinin resistance.
Moving forward, we designed
additional studies to understand the
mechanims underlying this safety
signal and continued very close
monitoring of liver function in patients
recruited in the trials. We also began
working with the West African Network
for Clinical Trials of Antimalarial Drugs
(WANECAM), led by Prof. Abdoulaye
Djimde, University of Science,
Techniques and Technologies of
Bamako, Mali. Pyramax was included
as one of four antimalarials trialled
in a large, phase IIIb/IV multicentre
study where patients were treated
with the same medicine more than
once during a 2-year follow-up period.
WANECAM was a 4,757-patient trial
that has generated a large data set.
As a result, Pyramax was shown to
be as well tolerated and efficacious on
re-treatment as on first administration
leading the EMA to provide positive
scientific opinion without geographical
or dosing restrictions for both the tablet
and granule formulations.
What was the value of the
partnership with MMV?
WJC: In addition to MMV’s scientific
expertise, MMV’s dedication and
high-level global networks have been
invaluable. MMV provided the know-
how to drive the scientific development
and the coordination to manage the
multi-nation clinical studies. They also
provided significant support to prepare
the dossier for submission to the EMA.
What are the next steps to
ensure Pyramax granules
reach as many vulnerable
children as possible?
WJC: Today, the partnership
is expanding beyond scientific
development into patient access. We
are working to support inclusion of
Pyramax in WHO’s Standard Treatment
Guidelines and Essential Medicines
List, which will support approvals in
malaria-endemic countries. At the
end of February 2016, Pyramax, as a
tablet formulation, had been registered
in 13 malaria-endemic countries, was
under review in 14, and was ready for
submission in many other endemic
countries. For the granule formulation,
we expect either new approvals or line
extension registrations in all countries
that have registered the tablet.
How did you feel when you
received the news from the
EMA?
IB: When it finally came, I was
absolutely overwhelmed with joy. It was
enormously satisfying to see that the
EMA assessed that the data supported
safety and efficacy of Pyramax on re-
treatment. I was also elated for the
project team and happy to have played
my part. In R&D you don’t often get to
work on projects that make it to the
end of development. I am thrilled to
continue to be part of the team that will
now ensure that Pyramax achieves the
widest possible patient access. That’s
what success is all about.
Q.
Q.
Q.
Q.
Q.
With Pyramax granules and tablets, we are proud that for the first time ever the paediatric formulation of an antimalarial was made available at the same time as the adult formulation with a label allowing unrestricted worldwide use.”
“
Dr Tim Wells Chief Scientific Officer, MMVEssential Medicines
upport approvals in
countries. At the
016, Pyramax, as a
had been registered
emic countries, was
4, and was ready for
any other endemic
ggranule formulation,
Chief Scientific Officer, MMV
33
5 | Getting better medicines to more people
34
Facilitating sustainable uptake of injectable artesunate
Globally around 438,000 people die each year of severe malaria, around 70% of whom are under the age of 5.1 In 2011, the WHO
recommended injectable artesunate (Inj AS) as first-line treatment for severe malaria, as it saves more lives than quinine.2,3 In anticipation
of this policy change and to help improve its access, MMV worked with Guilin Pharmaceutical to enable them to obtain WHO prequalification in
2010 for their Inj AS product – Artesun®.
MMV then quickly began work to increase access to Inj AS in Nigeria and the Democratic Republic of Congo – two countries with the highest
severe malaria burden in the world. Based on this experience, MMV established a severe malaria consortium with the Clinton Health Access
Initiative (CHAI) and the Malaria Consortium (MC) to implement the MMV-led Improving Severe Malaria Outcomes (ISMO) project. In 2013, the
project was awarded a UNITAID grant to continue scale-up in Nigeria and five other high-burden African countries (Cameroon, Ethiopia, Kenya,
Malawi and Uganda).
Slow uptake of injectable artesunate – the WHO-preferred
treatment for severe malaria – costs lives.
Mobilizing new financing, and developing and
coordinating a multi-stakeholder consortium to undertake
a multi-country 3-year scale-up of injectable artesunate.
ISSUE ACTION BY MMV AND PARTNERS
1 World Health Organization. World Malaria Report 2015. (2015): http://www.who.int/malaria/publications/world-malaria-report-2015/report/en/
2 Dondorp AM et al. “Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.” The Lancet. 376(9753):1647-57 (2010).
3 Dondorp A et al. “Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.” The Lancet. 366(9487): 717-25 (2005).
As the ISMO project comes
to a close in mid-2016,
what has been achieved?
As of December 2015, across the
six ISMO countries, the proportion
of injectable artesunate treatments
procured in the public sector compared
to quinine was 99.5% in 2015,
(compared to 16% in 2013), and the
average proportion of patients treated
with injectable artesunate versus
quinine was 85.5%. These figures alone
confirm that during the ISMO project, a
major shift to better treatment for severe
malaria took place. There were several
key steps along the way.
First, thanks to CHAI and MC, we were
able to ensure treatment policies were
updated in all of the countries.
Second, we have trained more than
18,000 health-care workers in more
than 1,650 health-care facilities –
approximately 50% more than the
original objective. Through the training
we were able to expand provision
of severe malaria care beyond large
hospitals.
Third, despite the initial limitations of in-
country medical quantification systems,
we were able to successfully quantify
the correct amount of drugs based
on need, so that there were almost no
stock-outs at the central medical stores.
And finally, we have sought to diversify
sources of quality Inj AS, identifying
additional manufacturers interested in
pursuing WHO prequalification, as a
means of ensuring competitiveness and
bolstering supply security in the market.
What have you learnt?
There has been a wealth of learning
that could be applied to other projects:
When implementing a new health
project, you need to consider
administrative lead times in
ministries of health – on average
it took 4 months for countries to
review and sign memorandums of
understanding.
Even if you are helping bring
critically-needed life-saving
medicines into a country, you may
have to pay customs duties or seek
appropriate waivers.
When it comes to quantifying
a newly launched product,
epidemiological data can serve as a
basis for first estimates, but it’s more
accurate to monitor distribution at
the health-care facility level following
the first deliveries.
Before you determine your
monitoring and evaluation indicators,
you need to ensure that appropriate
national systems for data collection
exist. Creating short-term parallel
systems to collect data just for
donor-funded projects is not optimal.
Training is key and most effective
when the drugs are already
available. When people are well
trained they are comfortable using
the drugs.
What was it like to work on
the ISMO project?
It has been a fantastic learning and
collaborative experience working
with our implementing partners,
CHAI and MC; our procurement
agent, Missionpharma; and the drug
manufacturer, Guilin. It’s also been very
satisfying to develop close working
relationships with both the Global
Fund and the US President’s Malaria
Initiative to harmonize our procurement
activities.
My overall feeling is extremely positive
– health workers who have used Inj AS
have consistently responded very
positively about their experiences
using the medicine. In addition, we
have already received feedback from
UNITAID, the major funder for this
project, that ISMO has achieved
its catalytic impact, in line with its
original objectives. I think when the
end users and the donor are satisfied,
the project team can be happy!
Alexis Kamdjou
MMV’s Country
and Procurement
Liaison Manager
based in
Cameroon
Alexis Kamdjou works with teams in the six countries providing technical and analytical support to implement the
UNITAID-funded ISMO project. As the project nears the end of its 3-year grant, Alexis talks about his experiences and
what has been learnt.
Q.
Q.
Q.
3535
Kamaragi’s storyTwo-year-old Kamaragi was suffering
from high fever when his mother brought
him to Luweero Hospital in Uganda. He
was diagnosed with severe malaria.
Fortunately, Kamaragi was given
injectable artesunate (Inj AS) and the next
day he was able to sit upright in bed and
his fever had gone. The worry and panic
on his mother’s face changed to relief as
she realized her son would survive.
Uganda has one of the highest burdens
of severe malaria in the world. Over
666,000 in-patient malaria cases were
registered in 2015 alone. On the same
day that Kamaragi was admitted, three
other children were also suffering from
severe malaria at Luweero Hospital;
fortunately, all of them received Inj AS
and recovered.
Thanks to the ISMO project, 1.5 million
vials of Inj AS were distributed throughout
Uganda, with the potential to treat up to
250,000 children like Kamaragi and to
save an additional 10,000 lives compared
to treatment with quinine.
“The roll-out of injectable artesunate has
helped Uganda to deal with the recent
malaria epidemic,” explained Kamaragi’s
physician Dr Byamukama. “Within the
public sector, the efforts have resulted in
a complete switch from quinine to Inj AS
to treat severe malaria.”
+
UGANDA
Since receiving
prequalification in 2010,
52.9 million vials of
Artesun® have been
shipped to malaria-
endemic countries,
saving an estimated
additional 300,000–
350,000 children’s lives
compared to treatment
with quinine.
“
Lelio Marmora UNITAID Executive Director
Children with severe malaria are typically given intravenous quinine, a cumbersome treatment which needs to be administered over a week. There is a better way: Inj AS is more effective than quinine in reducing malaria mortality in children and is quick to administer. Through its partners MMV, CHAI and the Malaria Consortium, UNITAID’s commitment of USD 34 million since 2013 to create a market for Inj AS is helping to improve severe malaria outcomes for millions.”
5 | Getting better medicines to more people
36
Buying time to save lives with rectal artesunate
WHO Guidelines for the treatment of malaria1 recommend
the use of rectal artesunate (RAS) for pre-referral
management of severe malaria. A single dose significantly
reduces the risk of death and permanent disability.2.3
Despite these recommendations, currently there is no
WHO-prequalified product.
Continuing the early work of WHO-TDR,4 defining
requirements for WHO-prequalification of rectal
artesunate; working with pharmaceutical partners, Cipla
and Strides Arcolab, to submit their products for WHO
prequalification and optimizing their use in low-resource
settings.
ISSUE ACTION BY MMV AND PARTNERS
1 World Health Organization. Guidelines for the treatment of malaria. Second edition. (2010): http://www.who.int/malaria/publications/atoz/9789241549127/en/
2 World Health Organization. Malaria in children under five. (2016): http://www.who.int/malaria/areas/high_ risk_groups/children/en/
3 Gomes MF et al. “Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial.” The Lancet. 373(9663):557-66 (2009).
4 WHO-TDR: World Health Organization Special Programme for Research and Training in Tropical Diseases.
5 World Health Organization. Rectal artesunate testing and delivery. (2016): http://www.who.int/tdr/research/malaria/rectal_artesunate/en/
How could rectal
artesunate improve
management of severe
malaria in Uganda?
Today, RAS has only been used in a
few operational research projects in
Uganda, but studies show it leads to
better patient outcomes. We still get
a large number of children with severe
malaria and the first point of contact
for care is a Community Health Worker
for around 60% of cases. These health
workers are voluntary and trained to
deliver basic medical care only, so
Inj AS would not be possible while RAS
would be. As such, in my view, this
intervention could have a big impact –
it could help to save lots of lives from
severe malaria at the community level.
What are the advantages of
using RAS as a pre-referral
intervention?
It’s really a groundbreaking intervention
– referral can take a long time with
our roads and transport system – we
don’t have ambulances. The mother
is usually the caregiver and often has
other children at home. It can take
time to figure out care of the remaining
children and how to transport the
sick child to hospital. RAS can hold
the ground and delay severe disease
until children can get recommended
treatment.
Do you have any concerns
about the implementation
of RAS?
There have been some concerns that
RAS could be misused; it is not intended
as curative treatment for malaria,
and administration of RAS must be
followed up with a full recommended
course of treatment (such as injectable
artesunate and/or ACT). And at the
community level, given the challenge
of patient transport, a framework will
need to be put in place to ensure that
referral to higher level facilities does
happen.
All medicines can be abused. Good
training in ethical conduct and
supervision is always a must with a
new intervention.
What are the advantages of
WHO prequalification from
your perspective?
It provides reassurance that there is a
good manufacturing process and the
product has good efficacy. Also, most
sources of funding can’t be assigned
to a product which is not prequalified
and so without it, access to finances
and therefore to the medicines, is
limited.
Dr Jimmy Opigo
Programme
Manager for
the National
Malaria Control
Programme in
Uganda
Dr Jimmy Opigo explains the potential benefits and drawbacks of RAS and the importance of WHO prequalification.
Q.
Q. Q.
Q.
If detected quickly, an uncomplicated malaria infection can almost always be treated successfully with highly effective
oral medicines artemisinin-based combination therapy (ACT); however, if left untreated it can quickly progress to severe
malaria, a life-threatening condition that can kill a patient within a few hours. The first point-of-care for many patients with
severe malaria is a community-level health-care worker or primary care facility. Patients presenting with severe malaria
should be treated as quickly as possible with injectable artesunate (Inj AS); however, most local health posts do not have
the drug or personnel trained in its administration, and so patients need to be referred to higher-level facilities. In such
cases, WHO recommends the use of RAS as a pre-referral intervention. RAS buys time before Inj AS can be administered
– and can mean the difference between life and death.5
With funding from UNITAID, MMV has been working with two Indian pharmaceutical companies, Cipla and Strides
Arcolab to obtain WHO prequalification for their RAS products. Reaching a significant milestone in 2015, both companies
submitted dossiers for review.
In February 2016, MMV, the US President’s Malaria Initiative, UNICEF, and Médecins Sans Frontières convened a
meeting in Nairobi, Kenya, inviting RAS stakeholders from 13 countries to discuss experiences and challenges relating to
implementation of this intervention. The recommendations and key findings from the meeting will help countries implement
RAS at the community level and save lives. MMV has also begun working with implementing partners and potential host
countries to design pilot introduction programmes for RAS.
37
Aiming for elimination
Mass Drug
Administration
(MDA):
Everyone in a
given population
receives
medicine to cure
any infection
(symptomatic or
asymptomatic)
and prevent
reinfection in the
short term.
Focal MDA
(fMDA) for
malaria:
Antimalarials
are provided to
anyone testing
positive and
anyone in the
household of the
person testing
positive.
Case
investigation:
Follow-up
of passively
detected,
lab-confirmed
cases (with
characterization
by age, sex,
residence, recent
travel that may
have led to
infection etc.)
and visit to their
households and
neighbourhoods
to seek and
treat other cases
and potentially
provide
prophylaxis.
Many people living in malaria-endemic regions
have been repeatedly exposed to malaria and
have developed semi-immunity. Thus, they might
carry the parasite yet not show any symptoms.
These asymptomatic carriers, along with ill
patients, constitute a human reservoir of parasites,
perpetuating the cycle of malaria transmission.
MDA is a tool to clear the human reservoir
of parasites and reduce malaria dramatically
in target communities, making elimination
feasible. MMV and partners are developing new
medicines with safety and efficacy profiles for
use in MDA.
ISSUE ACTION BY MMV AND PARTNERS
1 The ‘Team’ included the Zambia National Malaria Control Programme, provincial, district and local health officials, MACEPA & Tulane University School of Public Health.
Can you explain how MDA
was rolled out in Zambia?
A team of partners1 developed a pilot
project in Southern Province in a high-
transmission area, where in some places
50–60% of the population were infected
with malaria at the end of the transmission
season. We mapped out the health facility
catchment areas and randomly divided
them into three groups: MDA, fMDA
or the control group. All groups were
provided with good insecticide-treated
net coverage, indoor residual spraying,
malaria prevention during pregnancy,
and case management (with laboratory
testing, treatment and case investigation
where possible). We did two rounds of the
interventions each year for 2 years.
What were the key findings?
With the first year of data evaluation,
we saw enormous reductions in malaria
cases in health facilities, through
community outreach and in malaria
prevalence rates across all groups, with
the greatest reduction of around 90% in
the MDA group, 80% in the fMDA and
70% in the control. We were not surprised
to see the impact was so positive in the
control since they were getting the best
care, in terms of prevention and treatment
as mentioned, and possibly benefited
from a community effect – the overall
reservoir was reduced by the trial.
The aim was to shrink the case
burden enough so that individual case
investigation becomes feasible. We were
able to get to that point in a low
transmission area in 1 year with MDA.
What role do you
believe MDA has as we
move towards malaria
elimination?
It has a key role to play in getting us to
malaria elimination – I think of it as an
accelerator. It can take transmission from
fairly high to very low levels in a short time.
Our study also shows that you might also
get there with fMDA but it would probably
take longer than with MDA.
Why was Eurartesim®
(dihydroartemisinin-
piperaquine: DHA-PQP)
selected for the trial?
MDA benefits from a highly effective
and long-acting drug that both clears
infections and protects against reinfection,
which is why we chose Eurartesim. The
prophylactic effect is probably critical.
An acceptable safety profile is also
fundamental: you are giving medicines
to entire populations of people, most of
whom are not sick.
In the future, a single-dose drug would
be great; permitting a one-time directly
observed treatment enabling us to
ensure everyone receives a complete
treatment. That said, in Zambia, the vast
majority of people took all three doses as
recommended – perhaps because we
have been working there for some time
developing strong community relations,
another critical factor for successful MDA.
Dr Richard Steketee, Project Director,
MACEPA, explains what the
study revealed and the necessary
attributes of medicines for MDA.
Q.Q.
Q.
Q.
The Malaria Control and Elimination Partnership in Africa (MACEPA) has been working in Zambia for more than a
decade to support the country’s efforts to improve malaria control and ultimately eliminate malaria. Starting in 2014,
the MACEPA team collaborated with the National Malaria Control Programme and supported Zambian health officials to
conduct one of the largest MDA studies to date.
5 | Getting better medicines to more people
38
Fatou Touray’s story Mother and trader
“During the rainy season my children
usually suffer from malaria twice. When
they suffer, or a close relative suffers
from malaria, I have to stop everything
to help care for him or her. That means
all our farm and community activities are
affected.’’
“Children don’t like medicines and are
always afraid but we still give them the
SMC drugs. It has reduced the burden of
malaria in my house and family at large.
My children are not even suffering from
malaria anymore thanks to the SMC
medicines.”
GAMBIA
+
Protecting children at their most vulnerable
To protect children in areas of high seasonal malaria
transmission across the Sahel, the World Health Organization
(WHO) recommends seasonal malaria chemoprevention
(SMC) with sulfadoxine-pyrimethamine and amodiaquine
(SP+AQ) in regions where the combination remains
effective.1 Ensuring sufficient high-quality medicines are
available and correctly administered is a logistical challenge.
MMV and partners have produced SMC training materials
and are supporting their implementation in collaboration
with the SMC working group within the West Africa Roll
Back Malaria Network (WARN). Also, since 2014, as part
of the UNITAID-funded ACCESS-SMC Consortium,2 MMV
is supporting scale-up in seven countries in the Sahel.
ISSUE ACTION BY MMV AND PARTNERS
Prof. Jean Louis
Ndiaye
Cheikh Anta
Diop University,
Dakar, Senegal
What are the biggest
challenges in the
implementation of SMC?
The lack of a child formulation of SP+AQ
is a big challenge. It means we must
crush bitter tablets, making it very difficult
to administer them to youngsters. Also,
having enough medicines is challenging.
Last year we didn’t get the quantity we
needed to reach all the children.
Another challenge is the lack of a stan-
dardized approach to monitoring and
evaluation to measure the public health
impact of SMC and the prevalence of
molecular markers for drug resistance.
We know that pharmacovigilance sys-
tems are very weak in many countries,
which makes it difficult to know the num-
ber of adverse events associated with
SP+AQ, even if we know it is generally
well tolerated.
How are these challenges
being overcome?
Guilin has developed a dispersible tablet
that was granted a favourable opinion by
the Expert Review Panel for insertion on
the Global Fund list of malaria products.
This formulation can now be purchased
by international funders for the 2016
campaign. It was also submitted to WHO
prequalification and a verdict is expected
in 2016.
Guilin is confident that there will be
sufficient drugs available this year. Also,
MMV has signed an agreement with
a manufacturer, S Kant Healthcare, to
develop a second child-friendly tablet.
While ACCESS-SMC has developed a
quantification tool to help forecasting.
The SMC working group is harmonizing
training and ensuring all countries have
the same tools. One day of the SMC
training will be reserved to focus on
pharmacovigilance. It is also conducting
an impact and evaluation programme
with donor funding in selected areas.
However, the challenge remains to
obtain and maintain funding for these
activities in all areas that could benefit
from them.
Prof. Jean Louis Ndiaye was involved in the early SMC pilot studies and its scale-up in Senegal. He explains how the challenges to realizing its
maximum impact are being tackled.
Q. Q.
1 WHO Policy Recommendation: Seasonal Malaria Chemoprevention (SMC) for Plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-region in Africa. Geneva: World Health Organization Global Malaria Programme; March 2012: www.who.int/malaria/publications/atoz/smc_policy_recommendation_en_032012.pdf
2 The UNITAID-funded ACCESS-SMC Consortium includes: the Malaria Consortium (prime recipient), Catholic Relief Services (joint lead), MMV, Management Sciences for Health, Speak Up Africa and the London School of Hygiene & Tropical Medicine.
3 Cairns M et al. “Estimating the potential public health impact of seasonal malaria chemoprevention in African children.” Nat Commun. 3:881 (2012).
4 WHO/GMP Technical Expert Group On Preventive Chemotherapy, Geneva 4–6 May 2011. Report of the technical consultation on seasonal malaria chemoprevention: www.who.int/malaria/mpac/feb2012/smc_teg_report.pdf
5 Lubell Y et al. “Cost-effectiveness of parenteral artesunate for treating children with severe malaria in sub-Saharan Africa.” Bull World Health Organ. 89(7):504-12 (2011).
In some parts of Africa, annual malaria cases are concentrated in the 4-month rainy season. Around 39 million African children under 5 years of
age live in these regions and an estimated 152,000 die from malaria each year.3 Most of these children live in the Sahel and sub-Sahel regions
of Africa where SMC with SP+AQ has been shown to be a cost-effective solution to prevent around 75% of malaria episodes: high-quality SMC
drugs cost ~USD 1 per season, while inpatient care for a case of severe malaria is estimated to cost USD 12–75.3,4,5
In 2015, the ACCESS-SMC project reached 3 million children across the Sahel leading to reports of empty beds in malaria wards. In 2016, the
goal is to reach 6.5 million children.
39
Improving malaria chemoprevention and treatment during pregnancy
Every year, 125 million pregnancies around the world
are at risk from malaria.1 In Africa alone, approximately
10,000 women and 200,000 babies die annually as a
consequence.2 Pregnant women have an increased risk
of life-threatening outcomes, including cerebral malaria
or severe anaemia.3 To diminish the risk of malaria
during pregnancy, the World Health Organization (WHO)
recommends a specific chemoprevention strategy,
however, its acceptance and use is quite low. HIV-positive
pregnant women are particularly vulnerable, as, owing
to drug interaction concerns, there is no recommended
chemoprevention option for them. Additionally, there
are concerns about the risk of declining effectiveness
of the current chemoprevention option and a shortage
of pregnancy safety data for most of the currently
recommended malaria treatments.
1. Work to improve coverage of intermittent preventive
treatment in pregnancy (IPTp)4 with sulfadoxine-
pyrimethamine (SP) in areas where it remains effective.
2. Undertake a safety study in Tanzania testing
dihydroartemisinin-piperaquine (DHA-PQP) as an
alternative option for IPTp.
3. Gather data to better define the safety profile of
currently used artemisinin-based combination
therapies during pregnancy, particularly during the first
trimester when the fetus is most vulnerable.
4. Work with a leading biosimulation partner to predict
drug–drug interactions between widely used
medicines for HIV-positive pregnant women and future
malaria chemoprevention options.
ISSUE ACTION BY MMV AND PARTNERS
To protect pregnant women living
in areas of moderate-to-high
malaria transmission, for several years
WHO has recommended IPTp by
administering the drug sulfadoxine-
pyrimethamine (SP) ideally at a
minimum of three antenatal care visits,
at least a month apart. Unfortunately,
IPTp coverage is very low – only 24%
of pregnant women in sub-Saharan
Africa receive the minimum dosing.5 In
addition, there are worrying signs that
SP’s chemopreventive efficacy may be
undermined in the future by emerging
drug resistance. In line with current WHO
recommendations, MMV has supported
the Roll Back Malaria Partnership’s Call
to Action,5 an advocacy effort outlining
specific actions by national health
entities, donors, the pharmaceutical
industry and civil society to achieve
greater access to and acceptance of
IPTp where and while it is still effective.
Meanwhile, to address the need for
more research on new IPTp options,
MMV and the London School of Hygiene
& Tropical Medicine are conducting
a safety study of Eurartesim® (DHA-
PQP) in pregnant women in Tanzania.
Specifically, this study will closely
evaluate the cardiac safety of DHA-PQP
in this patient group, building on other
phase IV safety research that MMV and
partners have already conducted in
non-pregnant patients.
For treatment of malaria in pregnancy,
WHO recommends artemisinin-based
combination therapy (ACT) during
the second and third trimesters,6 but
additional data are needed to confirm
their safety and tolerability during the
first trimester. Additionally, the dose of
different ACTs needed during pregnancy
remains uncertain, given the significant
changes in the metabolism of expectant
women during the first trimester.
MMV is planning to establish a registry
that tracks outcomes of pregnant
women exposed to antimalarials to
build a more robust evidence base
about the impact of specific medicines
on pregnancy and new-born outcomes.
The first step will be to establish
this registry in Mozambique with the
Manhiça Foundation which will follow
women who receive DHA-PQP as part
of a Mass Drug Administration pilot
programme, if they discover they are
pregnant in the 2-month period that
follows. The data will enable us to better
understand the tolerability of DHA-PQP
during pregnancy.
1 Manyando C et al. “A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy.” Malaria J. 11:141 (2012).
2 Dellicour S et al. “Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study.”PLoS Med. 7(1):e1000221 (2010).
3 Schantz-Dunn J & Nour NM. “Malaria and pregnancy: a global health perspective”. Rev Obstet Gynecol. 2(3): 186–192 (2009).
4 IPTp is the administration of a full course of an effective antimalarial treatment. It should only be administered to pregnant women living at risk of malaria after their first trimester and at a minimum of 1-month intervals.
5 Chico M et al. “Global call to action: maximize the public health impact of intermittent preventive treatment of malaria in pregnancy in sub-Saharan Africa.” Malar J. 14(1):207 (2015).
6 Guidelines for the treatment of malaria. Third edition. Geneva: World Health Organization; (2015): http://apps.who.int/iris/bitstrem/10665/162441/ 1/9789241549127_eng.pdf
“
Dr Clara Menéndez Director of ISGlobal’s Maternal, Infant and
Reproductive Health Initiative
Malaria during pregnancy is a serious threat to maternal and neonatal health. The development of interventions for malaria control in this most vulnerable group is urgently needed. Given its position and mission, MMV has a strategic and fundamental role to play in addressing the unmet needs of malaria in pregnancy.”
6 | Financial view
40
As a not-for-profit Swiss foundation set up
under statutes dated 15 November 1999,
Medicines for Malaria Venture (MMV) is exempt
from cantonal and federal taxes and is the
equivalent of an exempt organization under
Section 501(c) (3) of the United States Internal
Revenue Code. Furthermore, from 1 January
2011, the Swiss Federal Council granted MMV
the status of ‘Other International Organization’
conferring certain privileges and immunities
including exemption from VAT in Switzerland –
representing an estimated additional contribu-
tion from Switzerland to MMV of up to one million
Swiss Francs (CHF) per annum.
Portfolio funding
MMV receives funding and support from government
agencies, private foundations, international
organizations, corporate foundations and private
individuals (Figure 3). MMV also receives indirect
investment from its partners, who contribute
expertise, human resources and facilities.
These funds are used to finance MMV’s portfolio
of research and development (R&D) projects to
develop new, effective and affordable medicines
for the treatment and prevention of malaria.
They also support targeted access and product
management (APM) interventions to help ensure
that vulnerable populations in malaria-endemic
countries can access new malaria medicines.
We estimate that for every USD 1 invested,
MMV leverages approximately USD 3.5 of R&D
value (i.e. USD 1 in matched funds for external
costs plus USD 1.50 in in-kind contributions). In
2015, our two largest donors, the Bill & Melinda
Gates Foundation and the UK Department for
International Development (DFID), extended
programmatic supplements to their already sig-
nificant long-term commitments, which were
renewed in 2013. Moreover, thanks to dynamic
financial management coupled with proactive
fundraising, MMV’s R&D portfolio and APM
activities for the year were realized. MMV’s drug
R&D and APM activities and corresponding
expenditures in 2015 (USD 57.3 million and
USD 13.7 million, respectively) were both
above those in 2014 (USD 49.5 million and
USD 8.7 million, respectively). Overall, MMV’s
total expenditure of USD 80.6 million increased
by 20% compared with USD 67.2 million in
2014, mainly thanks to the above-mentioned
generous supplements.
Since its foundation in 1999, MMV has spent
USD 709 million to build the world’s largest R&D
portfolio of new and innovative antimalarial
medicines. With partners, MMV has brought
forward six new antimalarials, some of which are
already being used to treat patients in malaria-
endemic countries. In addition, during 2015
the Drugs for Neglected Diseases initiative trans-
ferred its malaria portfolio to MMV, with MMV
taking on the responsibility for the lifecycle
mana gement of two additional launched products.
The business plan estimates a minimum
of USD 350 million over the period 2016–2020
to sustain this work. With approximately
USD 200 million available, (USD 157 million out-
standing committed pledges for 2016–2020
at the end of 2015, as well as USD 48 million
cash brought forward to 2016), the organization
is currently tracking a shortfall of USD 150 million
in 2018–2020. MMV has several pending
proposals to donors and remains active in its
resource mobilization and advocacy activities.
FINANCIAL
VIEW
6
Financial year to 31 December 2015
Figure 3: Total funding received/pledged from 1999 to 2020 – USD 893 million as at 31 December 2015
Bill & Melinda Gates Foundation 60.00%
United Kingdom Department for International Development (DFID) 14.50%
Netherlands Minister for Development Cooperation 3.90%
Wellcome Trust 3.30%
UNITAID 2.50%
United States Agency for International Development (USAID) 3.20%
Irish Aid 2.00%
Swiss Government SDC 1.90%
World Health Organization/Roll Back Malaria (WHO/RBM) 0.50%
National Institutes of Health (NIH) 1.30%
Spanish Agency for International Development 1.20%
Australian Government Department of Foreign Affairs and Trade (DFAT) 1.00%
Global Health Innovative Technology Fund (GHIT) 0.90%
World Bank 0.90%
ExxonMobil Foundation 0.80%
Rockefeller Foundation 0.60%
Newcrest Mining Limited 0.40%
Merck KGaA 0.40%
Norwegian Agency for Development Cooperation (NORAD) 0.20%
Malaria Consortium 0.20%
BHP Billiton 0.10%
Individual and other donors 0.10%
Direction de la Coopération Internationale de Monaco (DCI) 0.04%
EU CRIMALDDI 0.01%
41
Details
MMV income
2015 USD 86,788,114
2014 USD 79,221,703
2013 USD 62,662,422
2012 USD 57,984,195
2011 USD 67,285,068
2010 USD 58,122,675
2009 USD 42,180,117
2008 USD 55,148,885
2007 USD 76,965,380
2006 USD 30,618,703
2005 USD 44,770,355
2004 USD 28,705,652
2003 USD 21,712,944
2002 USD 10,586,792
2001 USD 13,599,677
2000 USD 7,606,949
Research & development expenditure
2015 USD 57,330,528
2014 USD 49,537,276
2013 USD 50,165,812
2012 USD 60,756,529
2011 USD 40,330,004
2010 USD 42,544,044
2009 USD 44,298,951
2008 USD 46,028,889
2007 USD 41,494,679
2006 USD 46,943,252
2005 USD 27,166,334
2004 USD 23,805,411
2003 USD 16,950,454
2002 USD 10,353,468
2001 USD 6,709,653
2000 USD 2,280,748
Management and auditing
Relationships with two major Swiss banks allow
us to effectively manage our global banking
relationships and diversify risk. The banks
provide services such as current accounts,
investment and cash management facilities in
multiple currencies. MMV’s accounts are audited
annually by KPMG.
Financial reporting standards
The 2015 consolidated financial statements
were prepared in compliance with Swiss GAAP
FER. Until 2013, MMV had followed
International Financial Reporting Standards
(IFRS). The transition to Swiss GAAP FER in
2014 did not significantly alter transparency
and disclosure. The organization’s operating
procedures are constantly updated in line with
evolving requirements.
The 2015 financial statements were also prepared
in compliance with the Swiss Code of Obligations.
Foundation capital
By 31 December 2003, the stipulated foundation
capital of USD 4 million was fully subscribed
(in a Swiss foundation it is a legal requirement
that the foundation capital should be constituted
without delay in order to provide a degree
of financial security for the foundation).
The foundation capital remained unchanged
at 31 December 2015.
Donations and pledges 2015
(see Note 6 Donations)
Cash donations received in the bank amounted
to a total of USD 88 million with income
recognized in the previous year (2014) of USD
2.1 million, income deferred from the previous
year (2014) of USD 5.8 million and income
deferred to the following year (2016) of USD
11.1 million. Current 2015 income, to be received
in early 2016 amounted to USD 5.8 million.
Income of USD 0.1 million was recognized from
MMV North America Inc.
Management and administration
Management and administration cost increases
were kept consistently low during 2015.
MMV’s staff headcount increased to 59 from 55
in 2014. The ratio of management and
administration expenditure to overall spending
decreased to 7.1% from 8.3% in 2014 (7.3%
from 8.6% in 2014 if board and stakeholders’
expenses are included).
Figure 4: MMV expenditure 2015
Total: USD 80.6 million
Financial year to 31 December 2015
R&D 71%
Access & Product Management 17%
General & Administration 7%
External Relations & Advocacy 4%
Foundation Board & Stakeholders 1%
6 | Financial view
42
New pledges received in 2015
Financial year ahead to December 2016
MMV operates in a complex multi-currency
environment. It receives the bulk of donations in
US Dollars and UK Pounds Sterling, and a
smaller portion in other currencies such as
Swiss Francs (CHF), Euros (EUR) and Australian
Dollars (AUD). Cash outflows for projects are
also mostly in USD, which is the standard
currency used in the various specific contractual
agreements signed with each project partner
and therefore a natural cover for financial
exchange risk. On the other hand, many
operational expenses are in CHF. The resulting
exposure or exchange risk is hedged, generally
in January of each year and according to the
budget, in order to provide a nominal fixed
average USD/CHF budget rate for the period.
The accounts are kept in US dollars.
The philosophy underlying MMV’s financial
management is that of prudent, conservative
control, including appropriate return on interim
treasury investments. Forecasting various long-
term funding and income scenarios enables
MMV to manage its growing R&D portfolio more
effectively. It also provides a baseline analysis for
fundraising activities aimed at financing the
portfolio in line with long-term projections.
Given the unsteady financial environment and
market conditions, it is evident that the portfolio,
cash flow and new potential fundraising
opportunities have to be managed dynamically
and seamlessly.
Focus on sustainability: R&D and APM
In 2015, MMV continued to prepare, scale-up
and launch activities to ensure market access to
medicines emerging from its pipeline. In
alignment with MMV’s partnership model,
access and product management activities
conducted with partners enable MMV to achieve
its overarching goal of major health impact from
its medicines. Moreover, in the context of
malaria elimination and eradication, a second
and critical series of investments are now
urgently needed to spur on R&D for the next-
generation antimalarial drugs to meet that goal.
Although fundraising remains successful and
significant additional funds were sourced in
2015, major fundraising efforts will be required
in 2016 and even more in 2017 and beyond, as
MMV strives to meet the projected financial
requirements of its growing portfolio.
Financial modelling
Financial modelling suggests that, in spite of
additional future funding pledges for MMV in
2016 and pending proposals to donors, future
R&D and APM activities will remain underfunded.
The long-term financial projections for future
MMV overall spending over 2016–2020 is USD
350 million. This figure represents a mix of R&D,
product launch and APM-related spending,
including much needed innovation in treatments
for malaria in pregnancy, Plasmodium vivax
malaria, transmission blocking and other
technologies for elimination and eradication.
These financial statements and all forward-
looking financial figures should be considered
as management’s best estimates based on
information available at the time of printing.
Financial tables
The financial tables and notes that follow are
extracted from the Swiss GAAP FER compliant
accounts.
Figure 5: MMV income and expenditure to date and scenario 2016–2020
0
10
20
30
40
50
60
70
80
90
100
110
120
USD
in m
illio
n
2000 2002 2003 2004 2007 2008 2009 2011 2012 2013 2014 2015 2016 2018 2019 2020201720052001 2006 2010
Carried forward from previous year
Total income for the year
Total expenditure for the year
DONOR Amount (in millions) Period
United Kingdom Department for International Development (DFID) £5.0 (USD 7.5) 2015–2016
WHO Consultative Expert Working Group(‘Exploiting the Pathogen Box’ project)
USD 1.4 2015–2016
Total (USD equivalent) 8.9
MMV is grateful for these and previous commitments from its many donors.
43
MMV CONSOLIDATED STATEMENT OF FINANCIAL POSITION
31 Dec 2015 31 Dec 2014
USD USD
ASSETS Notes
CURRENT ASSETS
Cash and Cash Equivalents 3 48 491 563 38 057 339
Donations Receivable 6 5 819 726 2 081 748
Project Reimbursements Receivable – –
Accounts Receivable 625 258 2 503 016
Tax Receivable 6 908 6 002
Prepaids 602 867 447 087
Prepaid R&D Commitments 7 2 011 373 2 288 560
Prepaid APM Commitments 7 1 129 558 3 234 746
Derived Financial Instruments 13 180 734 –
TOTAL CURRENT ASSETS 58 867 987 48 618 498
LONG-TERM ASSETS
Long Term Receivables 2 578 398 886 861
Guarantees 16 191 260 191 523
Fixed Assets, Net 4 421 101 313 595
TOTAL LONG-TERM ASSETS 3 190 759 1 391 979
TOTAL ASSETS 62 058 746 50 010 477
LIABILITIES AND CAPITAL & RESERVES
CURRENT LIABILITIES
Accrued R&D Commitments 7 7 701 012 6 823 803
Accrued APM Commitments 7 1 224 186 2 347 264
Deferred Income 6 11 100 125 5 759 025
Other Creditors 1 386 171 875 267
Accrued Expenses 1 830 471 1 724 238
Short-Term Provisions 5 511 543 450 056
Donations Reimbursement Payables 9 339 058 320 653
Derived Financial Instruments 13 200 373 –
TOTAL CURRENT LIABILITIES 24 292 939 18 300 306
RESTRICTED FUNDS
Restricted Operating Funds 10 888 037 10 435 263
TOTAL RESTRICTED FUNDS 10 888 037 10 435 263
CAPITAL & RESERVES
Foundation Capital 4 000 000 4 000 000
Unrestricted Operating Funds 22 877 770 17 274 908
TOTAL CAPITAL & RESERVES 26 877 770 21 274 908
TOTAL LIABILITIES AND CAPITAL & RESERVES 62 058 746 50 010 477
6 | Financial view
44
MMV CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME
2015 2014
Continuing Operations USD USD
INCOME Notes
DONATION REVENUES
Private Foundations & Individual Donors 53 276 366 43 215 524
UN Agencies 7 912 360 7 288 713
Government Agencies 23 697 931 25 152 286
Corporates & Corporate Foundations 1 507 188 1 367 836
Total Restricted Donation 25 875 249 24 516 099
Total Unrestricted Donation 60 518 596 52 508 260
TOTAL DONATION REVENUES 6 86 393 845 77 024 359
OTHER INCOME 9 394 269 2 197 344
TOTAL INCOME 86 788 114 79 221 703
EXPENDITURE
RESEARCH & DEVELOPMENT EXPENDITURE
Project Grants 7 43 872 944 37 609 518
Project-Related Variable Expenditure 7 12 903 996 11 533 558
Expert Scientific Advisory Council Expenses 553 588 394 200
TOTAL RESEARCH & DEVELOPMENT EXPENDITURE 57 330 528 49 537 276
ACCESS & PRODUCT MANAGEMENT EXPENDITURE
Project Expenditure 7 11 823 226 6 803 784
Access-Related Variable Expenditure 1 777 512 1 824 705
Access & Product Management Advisory Committee 78 447 104 494
TOTAL ACCESS & PRODUCT MANAGEMENT EXPENDITURE 13 679 185 8 732 983
EXTERNAL RELATIONS & ADVOCACY EXPENDITURE
ER&A-Related Variable Expenditure 3 041 891 2 652 442
Fundraising 20 012 43 619
Communications 184 298 173 515
TOTAL EXTERNAL RELATIONS & ADVOCACY EXPENDITURE 3 246 201 2 869 576
FOUNDATION BOARD & STAKEHOLDER EXPENDITURE 14 165 251 172 950
GENERAL & ADMINISTRATION EXPENDITURE
Staff-related Benefits/Compensation 8 3 483 653 3 439 573
Office and Occupancy 11 1 369 720 1 238 742
Travel Expenses 48 842 58 044
Professional and Legal Fees 159 413 77 859
Training, Education and Journals 46 366 23 940
IT expenses 344 175 497 180
Depreciation 4 160 388 105 574
Other 100 051 172 083
TOTAL GENERAL & ADMINISTRATION EXPENDITURE 5 712 608 5 612 995
OTHER EXPENSES 9 481 507 320 653
TOTAL EXPENDITURE 80 615 280 67 246 433
RESULT FROM OPERATING ACTIVITIES 6 172 834 11 975 270
Interest Income 155 962 101 405
Financial Expenses (142 882) (41 588)
Foreign Currency Translation Differences 10 (130 278) (1 337 363)
Net Financial Result (117 198) (1 277 546)
(LOSS)/SURPLUS FOR THE PERIOD 6 055 636 10 697 724
ALLOCATIONS
Transfer (To)/From Operations Reserve (452 774) (7 395 853)
Transfer (To)/From Donor Restricted Reserve (5 602 862) (3 301 871)
(6 055 636) (10 697 724)
45
MMV CONSOLIDATED STATEMENT OF CHANGES IN EQUITY
Balance at
1 Jan 2014
Internal Funds
Transfer
Gain for the
Period
Balance at
31 Dec 2014
Gain/(Loss) for
the Period
Balance at
31 Dec 2015
Restricted Operating Funds 7 525 410 (392 018) 3 301 871 10 435 263 452 774 10 888 037
TOTAL RESTRICTED OPERATING FUNDS 7 525 410 (392 018) 3 301 871 10 435 263 452 774 10 888 037
Foundation Capital 4 000 000 – – 4 000 000 – 4 000 000
Unrestricted Operation Funds 9 487 037 392 018 7 395 853 17 274 908 5 602 862 22 877 770
TOTAL UNRESTRICTED FUNDS 13 487 037 392 018 7 395 853 21 274 908 5 602 862 26 877 770
MMV CONSOLIDATED STATEMENT OF CASH FLOW
2015 2014
USD USD
Notes
(LOSS)/SURPLUS FOR THE YEAR 6 055 636 10 697 724
Adjustments for:
Increase/(Decrease) in Provisions 5 61 487 10 765
Depreciation 4 160 388 105 574
OPERATING RESULT BEFORE WORKING CAPITAL CHANGES 6 277 511 10 814 063
CASH FLOW FROM OPERATING ACTIVITY
(Increase) in Donations Receivable (3 728 369) (1 631 759)
Decrease/(Increase) in Project Balance Reimbursements – 5 710
(Increase)/Decrease in Accounts Receivable 1 876 308 (2 476 888)
(Increase)/Decrease in Tax Receivable (906) (700)
(Increase) in Project-Related Prepaid Expenses 7 2 380 475 (4 070 650)
(Increase)/Decrease in Prepaid Expenses (155 780) (103 116)
Increase in Accrued R&D Commitments 7 877 209 58 510
Increase in Accrued APM Commitments 7 (1 123 078) 1 800 580
Increase in Deferred Income 6 5 341 100 1 631 143
Increase in Other Creditors 511 144 103 922
(Decrease)/Increase in Accrued Expenses 106 233 (1 165 220)
Increase in Donations Reimbursement Payables 141 215 320 653
(Increase) in Long-Term Receivable (1 691 537) –
Unrealized Foreign Currency (Gain)/Loss 42 843 382 066
CASH FLOW RESULTING FROM OPERATING ACTIVITY 4 576 857 (5 145 749)
CASH FLOW FROM INVESTMENT ACTIVITY
Decrease/(Increase) in Guarantees 3 824 (5 201)
(Increase) in Derivative Financial Instruments 19 639 –
(Increase) in Fixed Assets 4 (267 895) (189 483)
CASH FLOW RESULTING FROM INVESTMENT ACTIVITY (244 432) (194 684)
NET (DECREASE)/INCREASE OF CASH AND CASH EQUIVALENTS 10 609 936 5 473 630
Cash & Cash Equivalents at Beginning of Year 38 057 339 32 954 528
Effect of Exchange Rate Fluctuations on Cash Held (175 712) (370 819)
Cash & Cash Equivalents at End of Year 48 491 563 38 057 339
6 | Financial view
46
1. ORGANIZATION
MEDICINES FOR MALARIA VENTURE (‘MMV’) is
a Swiss foundation, established as a not-for-profit
legal entity, registered in Geneva under statutes
dated 15 November 1999. It is managed by a
foundation council, a chief executive officer and
six senior managers.
With its head office in Geneva, the aim of MMV
is to bring public and private sector partners
together to fund, and provide managerial and
logistical support, for the discovery and devel-
opment of new medicines for the treatment and
prevention of malaria. The products should be af-
fordable and appropriate for use by populations
in developing countries.
As with all Swiss foundations, Medicines for
Malaria Venture is monitored by the Swiss Federal
Supervisory Board for Foundations.
2. SIGNIFICANT ACCOUNTING
POLICIES
The significant accounting policies adopted
by MMV in the preparation of the consolidated
financial statements are set out below.
Statement of compliance
The consolidated financial statements for the year
ending 31 December 2015 were approved for issue
by the MMV board on 12 March 2016.
The consolidated financial statements have
been prepared in accordance with the articles of
incorporation of MMV, the applicable provisions
of the Swiss Code of Obligations and the Swiss
Generally Accepted Accounting Principles (Swiss
GAAP FER/ RPC).
As donations from governments are not being ad-
dressed in the Swiss GAAP FER 21, the organization
has decided to retain the accounting treatment pre-
scribed by IAS 20, namely recognize income up to
the amount of expenditure allocated by government,
the difference being recognized as deferred income.
The consolidated financial statements have been
prepared on the historical cost basis, except where
a standard requires a different measurement basis.
The consolidated financial statements give a true
and fair view of the organization’s financial position,
the results of its operations and the cash flows.
Certain prior-year amounts have been reclassified
to conform with the current year’s presentation.
Basis of preparation
The consolidated financial statements are pre-
sented in US dollars, since the majority of MMV’s
activities are conducted in this currency (group
functional and presentation currency).
Fair value is the amount for which a financial as-
set, liability or instrument could be exchanged
between knowledgeable and willing parties in an
arm’s length transaction.
The preparation of consolidated financial state-
ments in conformity with Swiss GAAP FER
requires management to make judgements,
estimates and assumptions that affect the ap-
plication of policies and reported amounts of
assets and liabilities, income and expenditure.
The estimates and associated assumptions are
based on historical experience and various other
factors that are believed to be reasonable under
the circumstances, the results of which form the
basis of making the judgements about carrying
values of assets and liabilities that are not readily
apparent from other sources. Actual results may
differ from these estimates. If in the future such
estimates and assumptions, which are based on
management’s best judgement at the date of the
consolidated financial statements, deviate from
the actual circumstances, the original estimates
and assumptions will be modified as appropriate
in the year in which the circumstances change.
Judgements made by management in the appli-
cation of Swiss GAAP FER that have significant
effect on the consolidated financial statements
and estimates with a significant risk of material
adjustment in the next year are discussed below.
Foreign currency transactions
Transactions in foreign currencies are translated
at the foreign exchange rate ruling at the date of
the transaction. Monetary assets and liabilities
denominated in foreign currencies at the Consol-
idated Statement of Financial Position date are
translated to USD at the foreign exchange rate
ruling at that date. Foreign exchange differences
arising on translation are recognized in the Con-
solidated Statement of Comprehensive Income.
Non-monetary assets and liabilities that are
measured in terms of historical cost in a foreign
currency are translated using the exchange rate
at the date of the transaction.
The following exchange rates were used at year end:
2015
1 CHF = USD 1.00899
1 EUR = USD 1.09254
1 GBP = USD 1.48236
1 AUD = USD 0.72875
2014
1 CHF = USD 1.0105
1 EUR = USD 1.2155
1 GBP = USD 1.5532
1 AUD = USD 0.8156
Cash and cash equivalents
Cash and cash equivalents comprise cash bal-
ances and short-term money market deposits
with original maturities of three months or less.
Fixed or tangible assets
Fixed assets are stated at cost less accumulated
depreciation. Depreciation is charged to the Con-
solidated Statement of Comprehensive Income
on a straight line basis over the estimated useful
lives of the assets. The estimated useful lives of
assets are as follows:
Office furniture 5 years > CHF 1,000
Fixtures
and installations 3 years > CHF 1,000
Computers
and equipment 3 years > CHF 5,000
Impairment
The carrying amounts of MMV’s assets are re-
viewed at each Consolidated Statement of Finan-
cial Position date to determine whether there is an
indication of impairment. If any such indication ex-
ists, the asset’s recoverable amount is estimated.
An impairment loss is recognized in the Consoli-
dated Statement of Comprehensive Income when-
ever the carrying amount of an asset exceeds its
recoverable amount.
The recoverable amount of an asset is the greater
of its value in use and its fair value less costs to
sell. In assessing value in use, the estimated future
cash flows are discounted to their present value
using a pre-tax discount rate that reflects current
market assessments of time, value for money and
the risks specific to the asset.
Provisions
A provision is recognized in the Consolidated State-
ment of Financial Position when MMV has a present
legal or constructive obligation as a result of a past
event, and it is probable that an outflow of economic
benefits will be required to settle the obligation.
Foundation capital
The foundation capital is fully subscribed at USD
4,000,000 as stipulated under the original legal
statutes. Under normal circumstances, founda-
tion capital may be used during the year to meet
cash flow shortfalls, but should be replenished
before closing at year end. Foundation capital to-
gether with the residual operations reserve serves
to maintain the viability of the organization, for
6 months, until other funding sources can be found.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS AS OF 31 DECEMBER 2015
47
Revenue recognition
An unconditional grant is recognized as revenue
in the Consolidated Statement of Comprehen-
sive Income when the grant becomes receiv-
able. Any other grant which has performance,
timing or other conditions is recognized in the
Consolidated Statement of Financial Position as
revenue once the foundation has complied with
the stipulated conditions. If the conditions have
not yet been fully complied with, then this grant
component is reported as a contingent asset as
disclosed in Note 12. They are considered as
unrestricted funds, unless the donor stipulates a
specific restriction.
A reconciliation between donations received in
cash and income recognized in the Consolidated
Statement of Comprehensive Income is shown in
Note 6.
Government grants are recognized as income for
the allowable expenses incurred in the current
year. At year end, the difference between the in-
come recognized and the cumulative expenses
incurred is accounted for as deferred income.
When the donor wishes to see a donation allo-
cated to a specific cause, the donation is con-
sidered to be an allocated fund. Allocated funds
that have not been used at the end of the year are
presented in a separate section of the Consoli-
dated Statement of Financial Position.
Contributions in kind
Occasionally MMV receives donations in kind, pri-
marily in the form of free use of goods or services
or preferential discounts. These contributions in
kind are not stated in the Statement of Compre-
hensive Income as this type of contribution is dif-
ficult to valorize.
Operations reserve
The accumulated restricted and unrestricted
operation funds represent excess of core grants
over expenditure since the inception of MMV.
These funds are available to be utilized for future
operations and project funding costs in accord-
ance with the donor’s requirements.
Research and development expenditure
Expenditure and grants allocated for research
and development activities undertaken with the
prospect of gaining new scientific or technical
knowledge and understanding are recorded on
the basis of contracts with grantees. In the event
that a portion of a grant is unpaid at the year end,
it is included under current liabilities. Expenses
paid before year end for the following period are
recorded as Prepaid R&D Commitments in current
assets and as Prepaid in Note 7.
Regulatory and other uncertainties inherent in the
development of new products in this sector pre-
clude MMV from capitalizing development costs.
Income tax and status
MMV received exoneration from income tax from
the Geneva cantonal and Swiss federal authorities
from the year 2000 for an indeterminate period.
A further agreement was signed on 8 December
2010 with the Swiss Federal Council under new
provisions of the recently promulgated Swiss Host
State Act, to grant MMV certain privileges and im-
munities – effective as of 1 January 2011.
The principal advantages for MMV as a Swiss
foundation with ‘Other International Organization’
status are the following:
Exoneration from all direct and indirect
federal, cantonal and communal taxes
(this was originally acquired by decree with
the Geneva cantonal and Swiss federal
authorities, but now formalized directly with
the Swiss government within the accord);
Exoneration from VAT on all goods and
services acquired for the sole use of the
foundation within Switzerland and abroad;
Unrestricted access to work permits for non-
Swiss, non-EU nationals
MMV will deal directly with the Swiss Mission
in Geneva for all such issues.
Basis of consolidation
MMV has established a special purpose entity
(SPE) for fundraising in North America (MMV,
North America, Inc.). MMV does not have any
direct or indirect shareholdings in this entity.
An SPE is consolidated if, based on an evaluation
of the substance of its relationship with MMV and
the SPE’s risks and rewards, MMV concludes it
controls the SPE. The SPE is not fully controlled
by MMV, but was established under such terms
and conditions that it imposes strict limitations
on the decision-making powers of the SPE’s
management with the result that MMV receives
the majority of the benefits related to the SPE’s
operations and net assets while being exposed
to the majority of risks incident to the SPE’s
activities, and retaining the majority of the residual
or ownership risks related to the SPE or its assets.
MMV appoints the board members of the SPE.
In accordance with Swiss GAAP FER 30
and based on the facts above, MMV North
America Inc. is fully consolidated in these
consolidated financial statements on a line by
line basis since 2011.
List of organizations consolidated in 2014:
Transactions eliminated on consolidation
All intra-group balances and transactions, and
any unrealized gains and losses arising from intra-
group transactions, are eliminated in preparing
the consolidated financial statements.
Accounting estimates and judgements
Certain critical accounting judgements in
applying MMV accounting policies are described
below.
Revenue recognition – MMV enters into complex
grant contracts that contain numerous provisions
related to performance, reporting and spending.
These criteria are monitored by both the scientific
programme and finance teams to assess progress
according to grant milestones and objectives. The
evaluation of progress requires judgement, as it is
based on subjective evaluations and discussions
with programme participants and sponsors.
Research and development expenditure –
MMV’s research and development expenditure
is generally not direct expenditure, but is in the
form of grants and contracts with external parties
who perform certain tasks at their request.
These requests are formalized by contracts
and agreements that outline the requested
services and development effort. Progress
against expectations is difficult to measure, and
measurement criteria are generally not defined
in grant agreements. We review research plans
and activities regularly to adjust annual funding
levels prospectively. Additionally, actual research
and development timing and execution are often
different than the original plans. These factors
lead to subjectivity in the timing and recognition
of research and development expenditure.
Country United States of America
Name and domicile MMV, North America, Inc. Delaware
Functional currency USD
% controlled by MMV N/A
Direct/Indirect N/A
6 | Financial view
48
The fire insurance value of the tangible fixed assets is USD 1,785,912 (2014: USD 1,717,850).
4. FIXED ASSETS
The effective rates on deposits have moved within the following ranges:
3. CASH AND CASH EQUIVALENTS
31 December 2015 31 December 2014
USD USD
Cash 8 283 1 513
Bank Balances 44 483 280 34 055 826
Money Market Deposits 4 000 000 4 000 000
TOTAL CASH AND CASH EQUIVALENTS 48 491 563 38 057 339
2015 2014
Low % High % Low % High %
US Dollar (USD) 0.00 0.27 0.00 0.20
Swiss Franc (CHF) – 0.75 0.00 0.01 0.05
British Pound (GBP) 0.00 0.00 0.00 0.00
Euro (EUR) – 0.75 0.00 0.01 0.05
Australian Dollar (AUD) 0.00 0.00 0.00 0.00
2014 Fixtures & Office Computers Total
Installations Furniture & Equipment
USD USD USD USD
COST
At 1 January 2014 492 511 395 462 527 241 1 415 214
Additions 60 302 44 260 84 921 189 483
Disposals – (503) (13 111) (13 614)
AT 31 DECEMBER 2014 552 813 439 219 599 051 1 591 082
ACCUMULATED DEPRECIATION
At 1 January 2014 362 709 343 426 479 393 1 185 528
Charge for the Year 38 040 18 731 48 802 105 574
Disposals – (503) (13 110) (13 614)
AT 31 DECEMBER 2014 400 749 361 654 515 085 1 277 488
NET BOOK VALUE
AT 31 DECEMBER 2014 152 064 77 565 83 966 313 595
2015 Fixtures & Office Computers Total
Installations Furniture & Equipment
USD USD USD USD
COST
At 1 January 2015 552 813 439 219 599 051 1 591 083
Additions 24 760 231 111 12 501 268 372
Disposals (23 032) (1 704) (12 964) (37 700)
AT 31 DECEMBER 2015 554 541 668 626 598 588 1 821 755
ACCUMULATED DEPRECIATION:
At 1 January 2015 400 749 361 654 515 085 1 277 488
Charge for the Year 37 560 95 835 26 993 160 388
Disposals (23 032) (1 704) (12 486) (37 222)
AT 31 DECEMBER 2015 415 277 455 785 529 592 1 400 654
NET BOOK VALUE
AT 31 DECEMBER 2015 139 264 212 841 68 996 421 101
49
5. PROVISIONS
6. DONATIONS
Below is a summary of donations received or committed during 2015:
On the total donations recognized in the Consolidated Statement of Comprehensive Income, USD 112,240 were received through MMV, North America, Inc.
Unused Vacation Reserve Total Provisions
USD USD
BALANCE AT 1 JANUARY 2014 439 291 439 291
Use/Release 2014 (439 291) (439 291)
Allocation for the Year 450 056 450 056
BALANCE AT 31 DECEMBER 2014 450 056 450 056
Use/Release 2015 (450 056) (450 056)
Allocation for the Year 511 543 511 543
BALANCE AT 31 DECEMBER 2015 511 543 511 543
Cash
Received
2015
USD
Income
Recognized
during
Previous Year
USD
Income
Deferred from
Previous Year
USD
Income
Deferred to
Following Year
USD
Current Year
Income to be
Received
USD
Unrealized
Foreign
Exchange
Gain/(Loss)
USD
Total Income
as per
Statement of
Comprehen-
sive Income
USD
Bill & Melinda Gates Foundation 42 429 918 – – – – – 42 429 918
Bill & Melinda Gates Foundation (Innovation Fund) 810 000 – – – – – 810 000
Bill & Melinda Gates Foundation (Pathogen Box) 1 647 064 – – – – – 1 647 064
Bill & Melinda Gates Foundation (QIMR) 2 092 726 – – – – – 2 092 726
Wellcome Trust 800 000 – – – 800 000 – 1 600 000
GHIT 3 174 222 – – – 97 500 – 3 271 722
Swiss Government (DEZA/SDC) 1 716 000 – – – – – 1 716 000
UK Government (DFID) 16 866 640 – 5 759 025 (9 764 532) – – 12 861 133
US Government (USAID) 2 601 631 – – – 2 380 785 – 4 982 416
Irish Aid 1 123 000 – – – – – 1 123 000
Australian Government (DFAT) 2 629 666 – – (1 335 593) – – 1 294 074
Norwegian Government (NORAD) 589 550 – – – – – 589 550
National Institues of Health (NIH) 1 034 870 (343 844) – – 440 732 – 1 131 758
UNITAID 6 181 967 (1 241 557) – – 1 747 950 – 6 688 360
World Health Organization (WHO) 1 224 000 – – – – – 1 224 000
ExxonMobil 500 000 – – – – – 500 000
Newcrest Mining Limited 665 939 (236 619) – – 182 188 – 611 508
Malaria Consortium (SMC) 1 473 513 (157 817) – – – – 1 315 696
Merck KGaA 324 772 (98 911) – – 167 572 (752) 392 681
Individual Donors 112 240 (3 000) – – 3 000 – 112 240
TOTAL RECEIVED 87 997 718 (2 081 747) 5 759 025 (11 100 125) 5 819 726 (752) 86 393 845
6 | Financial view
50
7. P
RO
JE
CT
GR
AN
TS
Pro
jec
t N
am
e A
wa
rde
d 2
015
(US
D)
Fin
al A
llo
ca
tio
n
2015 (U
SD
)
Pa
id 2
015
(US
D)
Re
late
d t
o 2
015
pa
id in
2016
(US
D)
Pre
pa
id 2
015
for
2016 (
US
D)
Pro
jec
t P
art
ne
rs
Hit
Id
en
tifi
ca
tio
n 4
965 7
82
4 2
31 6
59
3 7
13 9
91
517 6
69
734 1
23
1P.
falc
iparu
m e
ryth
rocyt
ic s
tage in
hib
itors
147 9
69
28 8
81
(119 0
88)
147 9
69
119 0
88
Dund
ee U
niv
ers
ity,
UK
2P
K a
naly
tical c
hem
istr
y 4
9 9
80
49 9
80
24 7
55
25 2
25
−
Sw
iss B
ioq
uant
3B
ioFocus d
ivers
ity
libra
ry
32 3
55
12 3
55
12 3
55
−
20 0
00
Bio
Focus
4C
halle
nge G
rants
24 3
40
24 3
40
24 3
40
−
−
Med
icin
es for
Mala
ria V
entu
re
5P
ath
ogen B
ox
508 4
79
508 4
79
508 1
09
371
−
Evo
tec, TC
G L
ifesc
ience
6G
HIT
scre
enin
g p
rogra
mm
e 1
62 7
99
162 7
99
162 7
99
−
−
Griffi
th U
niv
ers
ity,
Austr
alia
7C
RO
DM
PK
50 9
57
50 9
57
50 9
57
−
−
Cyp
rote
x D
iscove
ry
8P
anto
thenate
deriva
tive
s (Tr
op
IQ)
146 8
83
146 8
83
−
146 8
83
−
Trop
IQ H
ealth S
cie
nce,
Neth
erland
s
9D
eve
lop
ment
of P.
viv
ax
liver
sta
ge (H
TS
) assay
80 9
05
79 6
95
79 6
95
−
1 2
10
National C
entr
e for
Bio
logic
al S
cie
nces,
Ind
ia
10
PfA
TP
4 s
cre
enin
g 7
706
7 7
06
−
7 7
06
−
Austr
alia
n N
ational U
niv
ers
ity
11
P. c
ynom
olg
i liv
er
(Kocken-B
PR
C)
200 0
00
200 0
00
200 0
00
−
−
BP
RC
, N
eth
erland
s
12
Early
Hit-t
o-L
ead
sup
port
LO
I to
be fund
ed
mid
-2015 (G
eneric C
od
e)
449 2
41
449 2
41
398 8
41
50 4
01
−
TC
G L
ifescie
nce,
Syn
gene,
Imp
erial C
olle
ge L
ond
on
13
Challe
nge G
rants
/Lib
rary
Purc
hase
1 2
72 9
98
1 0
25 1
66
1 0
25 1
66
−
247 8
32
Med
icin
es for
Mala
ria V
entu
re
14
Com
pound
acq
uis
itio
n/s
ynth
esis
193 8
17
118 8
17
38 9
17
79 9
00
75 0
00
TC
G L
ifescie
nce,
Ind
ia
15
Bio
Focus li
bra
ry 2
50,0
00 c
om
pound
s 5
68 9
00
568 9
00
568 9
00
−
−
Bio
focus
16
Daiic
hi-S
ankyo
antim
ala
rials
56 2
80
56 2
80
56 2
80
−
−
Griffi
th U
niv
ers
ity,
Austr
alia
17
OP
Bio
(O
kin
aw
a, Jap
an)
45 0
00
45 0
00
−
45 0
00
−
OP
Bio
, Jap
an
18
FN
DR
(B
angalo
re, In
dia
) 7
0 0
00
70 0
00
70 0
00
−
−
Found
ation for
Negle
cte
d D
isease -
FN
DR
19
In v
itro
assay
of anti P
. vi
vax
liver
sta
ge c
om
pound
s 1
96 8
31
196 8
31
196 8
31
−
−
Mahid
ol U
niv
ers
ity
20
Exp
loitin
g t
he P
ath
ogen B
ox
120 1
74
110 6
74
96 4
59
14 2
14
9 5
00
WH
O,
TC
G L
ifescie
nce
21
In v
itro
dru
g s
ensitiv
ity
of th
e z
oonotic p
ara
site
18 0
66
18 0
66
18 0
66
−
−
Lond
on S
chool o
f H
ygie
ne &
Tro
pic
al M
ed
icin
e
22
P. falc
iparu
m S
CID
in v
ivo t
esting D
FID
100 0
00
51 1
99
51 1
99
−
48 8
01
The A
rt o
f D
iscove
ry
23
Liv
er
sta
ge c
ap
acity
build
ing D
FID
375 0
67
162 3
75
162 3
75
−
212 6
92
Mahid
ol U
niv
ers
ity,
National C
entr
e for
Bio
logic
al S
cie
nces
24
Sta
sis
Box
87 0
35
87 0
35
87 0
35
−
−
Med
icin
es for
Mala
ria V
entu
re
Hit
to
Le
ad
255 5
39
237 8
77
212 3
87
25 4
90
17 6
62
25
Op
en S
ourc
e D
rug D
iscove
ry in
Austr
alia
30 6
19
30 6
19
18 6
39
11 9
80
−
Univ
ers
ity
of S
ydney
26
Long D
ura
tion H
ete
rocyc
les –
Bra
zil A
ntim
ala
rial P
roje
ct
77 2
73
59 6
11
59 6
11
−
17 6
62
Univ
ers
idad
e E
sta
dual D
e C
am
pin
as (U
NIC
AM
P)
27
Exp
loring p
roguanil
for
dela
yed
death
96 6
38
96 6
38
96 6
38
−
−
Griffi
th U
niv
ers
ity,
Austr
alia
28
Taked
a a
ntim
ala
rials
(S
him
ad
a, Ta
ked
a J
ap
an)
51 0
10
51 0
10
37 5
00
13 5
10
−
Shim
ad
a,
Taked
a J
ap
an
Le
ad
Op
tim
iza
tio
n 3
304 3
83
3 3
04 3
83
2 6
81 7
92
622 5
91
−
29
GS
K (m
inip
ort
folio
1)
1 5
00 0
00
1 5
00 0
00
1 5
00 0
00
−
−
GS
K
30
Nova
rtis
(m
inip
ort
folio
2)
388 0
00
388 0
00
388 0
00
−
−
Nova
rtis
Institu
te for
Trop
ical D
iseases
31
Sanofi
Ave
ntis (m
inip
ort
folio
4)
171 0
00
171 0
00
171 0
00
−
−
Sanofi
32
St
Jud
e/R
utg
ers
/US
F a
ntim
ala
rials
(N
IH fund
ing )
1 0
33 4
14
1 0
33 4
14
410 8
23
622 5
91
−
Rutg
ers
Univ
ers
ity, S
t Jud
e C
hild
ren’s
Rese
arc
h H
osp
ital,
Univ
ers
ity o
f S
outh
Flo
rida, N
ort
heast
ern
U
niv
ers
ity (N
IH fund
ing)
33
DP
I U
CT H
2L (am
inop
yrid
ine)
211 9
69
211 9
69
211 9
69
−
−
Technolo
gy
Innova
tion A
gency,
Univ
ers
ity
of C
ap
e T
ow
n
Dis
co
ve
ry P
latf
orm
Te
ch
no
log
ies (
Elim
ina
tio
n)
3 9
19 6
49
3 9
19 6
49
3 2
56 0
72
663 5
77
−
Cro
ss F
un
cti
on
al
2 7
85 7
98
2 7
85 7
98
2 3
10 9
02
474 8
96
−
34
Mala
ria L
ab
Resis
tance M
uta
nts
Fid
ock
115 0
77
115 0
77
115 0
77
−
−
Colu
mb
ia U
niv
ers
ity,
New
York
35
GS
K T
ransla
tional P
harm
acolo
gy
Gro
up
671 7
96
671 7
96
671 7
96
−
−
GS
K
36
Sw
iss T
rop
ical a
nd
Pub
lic H
ealth Institu
te (S
wis
s T
PH
) 6
72 8
29
672 8
29
323 8
25
349 0
05
−
Sw
iss T
rop
ical a
nd
Pub
lic H
ealth Institu
te (S
wis
s T
PH
)
51
37
Monash C
DC
O 2
57 3
84
257 3
84
193 6
65
63 7
19
−
Monash U
niv
ers
ity
38
CR
O C
hem
istr
y 4
91 0
00
491 0
00
491 0
00
−
−
Syn
gene
39
P. v
ivax
in v
itro resi
stance test
ing
20 0
00
20 0
00
20 0
00
−
−
Menzi
es S
chool o
f M
ed
ical R
esearc
h,
Austr
alia
40
Com
pound
managem
ent
45 5
60
45 5
60
43 6
52
1 9
08
−
SP
EC
S
41
Syn
gene p
ara
sitolo
gy
183 9
47
183 9
47
183 9
47
−
−
Syn
gene
42
Outs
ourc
ing b
ud
get
182 4
53
182 4
53
179 8
14
2 6
39
−
Med
icin
es for
Mala
ria V
entu
re
43
Fie
ld is
ola
tes r
esis
tance
40 0
00
40 0
00
40 0
00
−
−
Sw
iss
TP
H, C
entr
e S
uis
se d
e R
echerc
he S
cie
ntifi
que e
n C
ôte
d Iv
oire
44
Art
em
isin
in −
resis
tance in
vitro
105 7
50
105 7
50
48 1
24
57 6
26
−
Institu
t P
aste
ur
du C
am
bod
ge
P. v
ivax
Hyp
no
zo
ite
s 2
47 0
42
247 0
42
169 5
68
77 4
74
−
45
In v
ivo a
ssay
of com
pound
s w
ith h
em
oly
tic li
ab
ilitie
s 5
2 2
12
52 2
12
52 2
12
−
−
Sta
te U
niv
ers
ity
of N
ew
York
, U
psta
te M
ed
ical U
niv
ers
ity
46
Deve
lop
ment of a li
ver
stage P
. vi
vax
in v
itro a
ssay
141 5
19
141 5
19
64 0
45
77 4
74
−
Univ
ers
ity
of C
alif
orn
ia S
an D
iego,
School o
f M
ed
icin
e
47
Prim
aq
uin
e m
echanis
m 5
3 3
12
53 3
12
53 3
12
−
−
Univ
ers
ity
of Liv
erp
ool,
UK
Tra
nsm
issio
n B
loc
kin
g 4
77 8
53
477 8
53
366 6
46
111 2
07
−
48
Gam
eto
cyt
e a
ssay
deve
lop
ment and
scre
en (st
age s
pecifi
c)
142 8
53
142 8
53
107 8
96
34 9
57
−
Imp
erial C
olle
ge L
ond
on
49
Dru
g a
ssay
pla
tform
for
inhib
ition o
f P.
falc
iparu
m tra
nsm
issi
on s
tages
30 0
00
30 0
00
30 0
00
−
−
Trop
IQ H
ealth S
cie
nce,
Neth
erland
s
50
GS
K in
secta
ry
305 0
00
305 0
00
228 7
50
76 2
50
−
GS
K
Ch
em
op
rote
cti
on
/Pro
ph
yla
xis
408 9
56
408 9
56
408 9
56
−
−
51
Deve
lop
ment of a P
. b
erg
hei u
HTS
live
r st
age a
ssay
and
scre
enin
g o
f B
ioFocus
libra
ry 4
08 9
56
408 9
56
408 9
56
−
−
Univ
ers
ity
of C
alif
orn
ia S
an D
iego,
School o
f M
ed
icin
e
Pre
clin
ica
l D
eve
lop
me
nt
1 3
15 9
97
1 3
15 9
97
1 0
03 3
30
312 6
67
−
52
P218
617 0
89
617 0
89
504 1
81
112 9
09
−
Bio
tec T
haila
nd
53
DD
D498 (D
und
ee U
niv
ers
ity)
12 5
14
12 5
14
12 5
14
−
−
Dund
ee U
niv
ers
ity
54
DS
M421
469 3
94
469 3
94
269 6
36
199 7
58
−
Taked
a
55
SJ733
217 0
00
217 0
00
217 0
00
−
−
St
Jud
e,
ES
AI, G
HIT
Ph
ase
I 3
119 4
56
3 1
19 4
56
2 7
60 4
06
359 0
50
−
56
MM
V390048
2 0
24 4
31
2 0
24 4
31
1 7
89 7
97
234 6
34
−
Univ
ers
ity
of C
ap
e T
ow
n,
Technolo
gy
Innova
tion A
gency
57
Intr
are
cta
l Art
esunate
(U
NIT
AID
) 5
33 9
47
533 9
47
508 0
05
25 9
42
−
Cip
la,
Str
ides A
rcola
b
58
DS
M265−
OZ
439 c
om
bo
561 0
78
561 0
78
462 6
04
98 4
74
−
Queensla
nd
Institu
te o
f M
ed
ical R
esearc
h
Pro
of
of
Co
nc
ep
t (p
ha
se
II)
−
−
−
−
−
Tra
nsla
tio
na
l P
latf
orm
Te
ch
no
log
ies (
Elim
ina
tio
n)
2 7
18 9
16
1 9
34 6
94
1 9
17 4
78
17 2
16
784 2
22
59
The P
ilot
Hum
an M
ala
ria C
halle
nge s
tud
y 4
65 8
42
465 8
42
449 5
08
16 3
34
−
Queensla
nd
Institu
te o
f M
ed
ical R
esearc
h
60
Transm
issio
n b
lockin
g m
od
els
1
39 7
57
139 7
57
138 8
75
882
−
Clin
ical N
etw
ork
Serv
ices
61
QIM
R c
ap
acity
and
qualit
y sup
port
2 1
13 3
16
1 3
29 0
94
1 3
29 0
94
−
784 2
22
Queensla
nd
Institu
te o
f M
ed
ical R
esearc
h
Ph
ase
IIa
2 8
68 5
09
2 8
68 5
09
2 4
01 9
51
466 5
58
−
62
DS
M265−
DH
OD
H in
hib
ito
rs 2
868 5
09
2 8
68 5
09
2 4
01 9
51
466 5
58
−
GH
IT, Ta
ked
a
Ph
ase
IIb
16 0
21 8
99
16 0
21 8
99
11 3
36 8
90
4 6
85 0
09
−
63
OZ
439
15 2
17 0
12
15 2
17 0
12
11 3
36 8
90
3 8
80 1
22
−
Sanofi
64
KA
E 6
09
804 8
87
804 8
87
−
804 8
87
−
Nova
rtis
Institu
te for
Trop
ical D
iseases
Ph
ase
III
3 7
28 4
57
3 7
28 4
57
3 7
40 0
74
(11 6
17)
−
65
Tafe
noq
uin
e for
P. v
ivax
rela
pse
pre
ventio
n 2
768 1
23
2 7
68 1
23
2 7
79 7
40
(11 6
17)
−
GS
K
66
Paed
iatr
ic tafe
noq
uin
e for
P. v
ivax
rela
pse
pre
ventio
n 9
60 3
34
960 3
34
960 3
34
−
−
GS
K
Ph
ase
IV
3 6
65 7
30
3 1
90 3
65
3 1
47 5
63
42 8
02
475 3
65
67
Pyr
am
ax
® (p
yronarid
ine-a
rtesu
nate
) 1
22 2
67
122 2
67
111 4
83
10 7
84
−
Shin
Poong P
harm
aceutical C
o
68
Safe
ty/e
fficacy
of re
treatm
ent w
ith A
CTs
(W
AN
EC
AM
stu
dy)
2 8
90 6
67
2 4
15 3
01
2 3
92 3
51
22 9
50
475 3
65
Univ
ers
ity
of B
am
ako
69
Pyr
am
ax®
(p
yronarid
ine-a
rtesu
nate
) new
paed
iatr
ic form
ula
tion
283 2
26
283 2
26
274 1
59
9 0
68
−
Shin
Poong P
harm
aceutical C
o
70
Ext
end
ed
Eth
iop
ia m
ala
ria trial c
ap
acity
build
ing
369 5
70
369 5
70
369 5
70
−
−
Univ
ers
ity
of V
ienna
TO
TA
L R
&D
45 8
84 3
17
43 8
72 9
44
36 1
71 9
33
7 7
01 0
12
2 0
11 3
73
6 | Financial view
52
Project grants represent the awards to the
projects as specified above, directly managed
and supervised by MMV.
Project-related variable expenditures include all
legal advice/services for contract negotiations
(IPR), organization and travel for project meetings/
reviews, MMV scientific personnel compensation
and various scientific project consultancies.
Expenditure for this MMV support totalled USD
12,903,996 and USD 11,533,558 in 2015 and 2014,
respectively.
Project reimbursements receivable
These refer to unused balances of project grants
previously committed, which are returned to
MMV by the project partners as stipulated in the
individual contractual agreements on termination
or reorganization of R&D projects.
8. PERSONNEL EXPENSES
There were 57 employees at 31 December 2015,
excluding temporary staff members (2014: 55).
The pension plan covers all employees for death
and disability benefits. Cover for retirement
benefits begins in the year following each
employee’s 24th birthday. The retirement pension
is based on the level of the retirement credits, the
interest rate to be credited and the conversion
rate to be applied at retirement age. Risk benefits
are related to pensionable salary.
The occupational benefits are provided by a
collective foundation, Profond, according to a
defined contribution benefit plan: investment
yield has no impact on premiums; the employer
does not guarantee the benefit amount. The plan
is funded by the contribution of MMV and the
employees.
7. PROJECT GRANTS (CONTINUED)
Pension Plan Statistics 2015 2014
USD USD
Capital Ratio (%) 105.9 107.4
Economic Part of the Entity as of 1 January – –
Economic Part of the Entity as of 31 December – –
Occupational Benefits Included in Personnel Expenditures 1 764 783 1 703 149
Pension Fund (Asset)/Liability – (320)
Awarded
2015 (USD)
Final
Allocation
2015 (USD)
Paid 2015
(USD)
Related to
2015 paid in
2016 (USD)
Prepaid
2015 for 2016
(USD)
Project Partners
Introduction of New Product/Oversee
Launched Product11 132 558 10 185 765 9 120 857 1 064 908 946 793
1 Policy Revision 35 113 35 113 35 113 – – Government of Democratic Republic of the Congo
2 Eurartesim® 235 803 181 352 180 726 626 54 451 National Institute Malaria Research, India; Imperial
College London; Sigma-Tau Industrie Farmaceu-
tiche Riunite, Italy
3 Pyramax® General 11 857 11 857 11 857 – – Medicines for Malaria Venture
4 Pyramax® CANTAM Study 38 167 38 167 28 167 10 000 – Central African Network on Tuberculosis, HIV/AIDS
and Malaria
5 Injectable Artesunate – General 92 516 72 516 42 516 30 000 20 000 Medicines for Malaria Venture
6 Malaria in Pregnancy (IPTp) 481 961 271 082 117 871 153 211 210 879 London School of Hygiene & Tropical Medicine
7 OZ439 7 642 7 642 7 642 – – Medicines for Malaria Venture
8 Seasonal Malaria Chemoprevention 168 327 168 327 127 327 41 000 – RBM West Africa sub-Regional Network (WARN)
9 Improving Severe Malaria Outcomes 9 976 838 9 315 375 8 492 908 822 467 661 463 Clinton Health Access Initiative; Malaria Consortium;
MissionPharma
10 RAS General 82 587 82 587 74 983 7 604 – Cipla Ltd; Strides Pharma Global Pte. Ltd
11 ASMQ – Low Cost, Paediatric, Market Assessment 1 748 1 748 1 748 – – Cipla Ltd
Input to R&D 649 489 466 724 460 904 5 820 182 765
12 VIVAX – Market Research to Support Tafenoquine 71 998 71 998 71 998 – – GlaxoSmithKline Services
13 VIVAX – Strategy Development 390 857 240 883 240 883 – 149 974 World Health Organization
14 India Comprehensive Case Management Pilot 186 634 153 844 148 024 5 820 32 791 National Institute Malaria Research India; NVBCDP
Odisha
Gather & Generate Information 499 400 499 400 419 152 80 248 –
15 Market Intelligence - General 243 462 243 462 178 964 64 499 – BroadReach Healthcare GmbH; ec4u expert
consulting (Schweiz) ag
16 Market Volumes (Market Size & Segmentation) 188 437 188 437 172 688 15 749 – Government of Zambia; Government of Uganda,
IMS Health
17 SMS for Life – Tanzania 67 500 67 500 67 500 – – Swiss TPH
New Projects/Pilots 485 899 485 899 439 290 46 609 –
18 Newcrest Alliance 2 228 2 228 2 228 – – Newcrest Mining Ltd
19 Mass Drug Administration Programming (Lihir) 478 487 478 487 431 878 46 609 – Newcrest Mining Ltd; ISGlobal Barcelona Institute
For Global Health
20 DSM265 5 185 5 185 5 185 – – Medicines for Malaria Venture
Access Events & Misc. Project Costs 185 438 185 438 158 836 26 602 –
21 Events & Conferences 62 856 62 856 62 856 – – Medicines for Malaria Venture
22 Miscellaneous Project Costs 122 582 122 582 95 980 26 602 – Medicines for Malaria Venture
TOTAL 12 952 784 11 823 226 10 599 040 1 224 186 1 129 558
53
2015 2014
USD USD
Less than One Year 917 372 919 654
Between One and Five Years 1 326 643 2 240 648
More than Five Years – –
TOTAL 2 244 015 3 160 302
9. OTHER INCOME AND OTHER EXPENSES
In the course of 2015 MMV reimbursed an amount of USD 461,868 to a donor,
the Global Health Initiative Technology Fund (GHIT), owing to the period-termination
earmarked grant funded by GHIT. This amount represented the unused part of a grant
received in 2014.
10. FOREIGN CURRENCY TRANSLATION DIFFERENCES FOR FOREIGN
OPERATIONS
In order to minimize the potential adverse effect of foreign exchange fluctuations, the
MMV liquidity is deposited in bank accounts denominated in foreign currencies pro rata
to the breakdown of total expenditure by currency (natural hedging).
11. LEASES
Non-cancellable operating lease rentals are payable as follows:
MMV has several operating leases. These leases generally run for a period of 5 years,
with an option to renew the lease after that date. During the year ended 31 December
2015, USD 952,038 were recognized as an expense in the Consolidated Statement of
Comprehensive Income in respect of operating leases (2014: USD 920,577).
12. CONTINGENT ASSETS
As per current contractual agreements, and depending on satisfactory reporting to
donors, contingent assets related to donations are as follows:
OTHER INCOME 2015 2014
USD USD
Project Reimbursements from Previous Years – 2 100 000
Royalties 289 690 25 000
Tax at Source Commission 25 650 28 855
Other 78 929 43 488
OTHER INCOME 394 269 2 197 343
OTHER EXPENSES 2015 2014
USD USD
Donation Reimbursement (461 868) (320 653)
Derivatives Financial Instruments (19 639) –
OTHER EXPENSES (481 507) (320 653)
FOREIGN EXCHANGE GAIN/(LOSS) 2015 2014
USD USD
Exchange Gain/(Loss) from CHF 440 534 (769 580)
Exchange Gain/(Loss) from EUR 32 085 (93 629)
Exchange (Loss) from GBP (401 762) (479 089)
Exchange (Loss)/Gain from AUD (201 135) 4 935
FOREIGN EXCHANGE (LOSS) (130 278) (1 337 363)
2015 2014
USD USD
Less than One Year 69 259 235 74 331 769
Between One and Five Years 95 611 540 133 256 162
More than Five Years – –
TOTAL 157 870 775 207 587 931
6 | Financial view
54
13. DERIVATIVE FINANCIAL INSTRUMENTS
Derivative financial instruments used for hedging
balance sheet items are recognized at fair value
on the date a derivative contract is entered into
and are recorded as other receivables or other
current liabilities. Derivatives are subsequently
re-measured to their current fair value at each bal-
ance sheet date, with unrealized gains and losses
recognized in the income statement.
MMV uses currency options to hedge its expo-
sure to foreign currency risk.
14. RELATED PARTIES
MMV has a related party relationship with its
board members, executive officers and MMV
North America Inc.
Board members serve on a voluntary basis and
receive no remuneration. They are compensated
for travel and accommodation for participation
in board meetings and receive a per diem
allowance to cover incidental expenses during
these events.
15. RISK MANAGEMENT
The foundation council has overall responsibility
for organizing and supervising risk management.
The audit committee monitors management’s ap-
proach to risk management in compliance with
the organization’s principles and procedures and
verifies that risks are managed appropriately in
light of the current risks faced by the organiza-
tion. Based on a risk identification carried out pe-
riodically, MMV’s essential risks are assessed in
respect of likelihood and impact and documented
in a risk analysis report. The management has the
responsibility to monitor and supervise the sub-
stantial risks.
For risks related to accounting principles and
financial reporting, a risk analysis was carried out.
Controls in line with the Internal Control System
have been defined and measures resulting from
this have been implemented in order to minimize
the risks related to accounting principles and
financial reporting.
16. GUARANTEES
Guarantees concern office rental only and are re-
coverable on vacating the premises subject to the
prevailing contracts.
17. CAPITAL COMMITMENTS
AND CONTINGENCIES
MMV encounters certain risks and uncertainties
in conducting its affairs. These risks and uncer-
tainties have financial statement implications. In
all instances, these have been considered in the
consolidated financial statements, despite the fact
that the outcomes of these uncertainties cannot
be predicted with absolute certainty. Management
has concluded that provisions for these risks are
appropriate, and any adverse resolution of these
uncertainties will not have a material impact on the
financial position or results of the foundation.
18. AUDITORS
KPMG SA, Geneva, has been MMV’s statutory
auditor since the fiscal year 2003. Following a
competitive bidding in 2012, KPMG was reap-
pointed as the statutory auditor. The current lead
auditor, Pierre-Henri Pingeon, has acted in this
capacity since 2010.
During the fiscal year 2015, MMV paid a total
of USD 210,846 (2014, USD 153,502) to its
auditors. This amount was split as follows:
• Audit services (including special audit reports to
donors): USD 182,869 (2014: USD 153,502);
• Other services: USD 27,977 (2014: USD nil).
19. SUBSEQUENT EVENTS
No events have occurred between balance date
and the date of this report that require adjustment
to, or disclosure in, these financial statements.
2015 2014
Positive Value Negative Value Purpose Positive Value Negative Value Purpose
Options Currency Transactions 180 734 (200 373) Hedging – – N/A
TOTAL FINANCIAL INSTRUMENTS 180 734 (200 373) – – – –
BOARD MEMBERS 2015 2014
USD USD
Board members and meetings
165 251 172 950
55
REPORT OF THE AUDITORS TO THE BOARD OF MMV
56
Dr Dennis Schmatz
Former Vice President,
Head of Tsukuba
Research Institute,
Merck-Banyu Research
Laboratories, Japan
Dr David Bowen
Independent Advisor, USA
Mr Ray Chambers
United Nations Secretary-
General’s Special Envoy
for Health in Agenda
2030 and for Malaria;
Co-Founder of Malaria
No More, USA
Dr David Reddy
CEO, MMV, Switzerland
Ms Wendy Taylor
Director, Center for
Accelerating Innovation
and Impact at USAID,
USA
MMV North America Inc. Board
Dr Dennis Schmatz
Former Vice President,
Head of Tsukuba
Research Institute,
Merck-Banyu Research
Laboratories, Japan
Mr Ray Chambers1
United Nations Secretary-
General’s Special Envoy
for Health in Agenda
2030 and for Malaria;
Co-Founder of Malaria
No More, USA
Mr Per Wold-Olsen2
Chairman of MMV
Board, former President
of Human Health
Intercontinental Region,
Merck & Co., Inc., Middle
East & Africa; former
Member of Merck’s
Management Committee;
Chairman GN Store
Nord A/S, Denmark;
Board Member of Gilead
Sciences Inc., USA; Board
Member of Novo A/S and
Exiqon A/S, Denmark
Mr Alan Court
Senior Advisor to the
United Nations Secretary-
General’s Special Envoy
for Health in Agenda 2030
and for Malaria (Board
observer)
Dr David Brandling-
Bennett
Former Senior Advisor,
Malaria, Bill & Melinda
Gates Foundation, USA
Dr Robert Newman
Country Director, US
Centers for Disease
Control and Prevention,
Cambodia; Formerly
Director of Global Malaria
Programme, WHO
Mr Gabriel Jaramillo
Former General Manager
of the Global Fund to
Fight AIDS, Tuberculosis
and Malaria, Switzerland
Prof. Michael Ferguson3
Regius Professor of Life
Sciences and Associate
Dean for Research
Strategy, University of
Dundee, Scotland
Dr Winston Gutteridge
Former Chief, Product
R&D, Special Programme
for Research and Training
in Tropical Diseases,
WHO, Switzerland
Dr David Reddy
CEO, MMV, Switzerland
Dr Wendy Sanhai
Associate Professor
(adj), School of Medicine,
Duke University, USA
Ambassador
(Dr) Konji Sebati
CEO, Innovative
Pharmaceutical
Association of South
Africa, Johannesburg,
South Africa
Dr Ernest Darkoh3
Chairman & Founding
Partner, BroadReach
Healthcare, South Africa
Dr Pedro Alonso,
Director, WHO Global
Malaria Programme,
Switzerland
Ms Joy Phumaphi,
Co-Chair of the
Independent Expert
Review Group for Every
Woman Every Child; Chair
of the Global Leaders
Council for Reproductive
Health; and Executive
Secretary of ALMA, USA
From left to right – back row followed by front
Not pictured:
MMV Board
Behind the scenes
7
1 After 4 years as Chairman of MMV’s Board of Directors, in November 2015, Mr Ray Chambers, the United Nations Secretary-General’s Special Envoy for Financing the Health Millennium Development Goals and for Malaria, stepped down, entrusting the role to MMV’s Vice Chair, Mr Per Wold-Olsen. The appointment of Mr Wold-Olsen as Chairman was ratified by the Board of Directors. Mr Chambers will continue to serve on the MMV Board as a non-Executive Director.
2 Mr Per Wold-Olsen, former President of Human Health Intercontinental Region, Merck & Co., Inc, joined MMV’s Board in 2008 and has been Vice-Chair since May 2013. Mr Wold-Olsen holds an MBA and has extensive global leadership experience and knowledge of the health-care industry from his many years in the pharmaceutical industry. His extensive expertise encompasses product development, commercialization, and developing world and access issues.
3 Dr Fatoumata Nafo-Traore, Executive Director of WHO RBM, resigned from the MMV Board.
Prof. Mike Ferguson and Dr Ernest Darkoh were re-elected for second and third terms, respectively.
57
Expert Scientific Advisory Committee (ESAC)
Dr John Pottage
Co-Chairman MMV
ESAC (Development);
Chief Scientific and Medi-
cal Officer, ViiV Healthcare,
USA
Dr Dennis Schmatz
Co-Chairman MMV
ESAC (Discovery); former
Vice-President, Head of
Tsukuba Research
Institute, Merck-Banyu
Research Laboratories,
Japan
Dr Aileen Allsop
Former Vice-President
for Science Policy, R&D,
AstraZeneca, UK
Prof. Thomas Baillie
Vice Provost, Strategic
Initiatives, University of
Washington, USA
Dr Tesfaye Biftu
Principal Scientist, Merck
and Co., USA
Dr Robert Clay
Consultant, Highbury
Regulatory Science
Limited and Chief
Regulatory Officer,
Kinapse Ltd., UK
Prof. Umberto
D’Alessandro
Theme Leader, Disease
Control and Elimination,
Medical Research Council,
the Gambia
Dr Michael Dunne
Chief Medical Officer,
Durata Therapeutics, USA
Prof. Paul Fish
Chair of Medicinal
Chemistry, University
College London, UK
Prof. Kasturi Haldar
Rev. Julius Nieuwland,
CSC Professor of
Biological Sciences,
Director, Center for
Rare and Neglected
Diseases, University
of Notre Dame, USA
Prof. Dennis Kyle
Distinguished University
Health Professor, College
of Public Health, University
of South Florida, USA
Dr Marcus Lacerda
Director of Learning and
Research at the Fundação
de Medicina Tropical
Dr Heitor Vieira Dourado,
Brazil
Prof. John Lambert
Chief Medical Officer,
Global Head Medical
Affairs and Consulting,
PAREXEL International, UK
Dr Mary Mader
Senior Research Advisor,
Discovery Chemistry
Research and
Technologies, Eli Lilly
and Company, USA
Dr Christine Manyando
Head of Public Health
Department, Tropical
Diseases Research
Centre, Zambia
Dr George Mooney
KGM Pharma Consulting
LLC, USA
Prof. François Nosten
Director, Shoklo
Malaria Research Unit,
part of the Wellcome
Trust–Mahidol–Oxford
University Tropical
Medicine Research
Programme, Thailand
Dr Paul Reider
Pharmaceutical Specialist
and Lecturer, Department
of Chemistry, Princeton
University, USA
Dr David Roberts
Independent Scientific
Consultant, UK
Prof. Dennis Shanks
Army Malaria Institute,
Australia
Dr Peter Siegl
Director, Siegl Pharma
Consulting LLC, USA
Dr Sodiomon Sirima
Centre National de
Recherche et de
Formation sur le
Paludisme, Burkina Faso
Dr Per Sjoberg
Partner, Eureda, Sweden
Prof. Dennis Smith
Former Vice-President,
PGRD, Pfizer, UK
Dr Klaus Urbahns
Head of Discovery
Technologies at Merck
Group, Germany
Dr Elizabeth Vadas
InSciTech Inc, Canada
Dr Neena Valecha
Director, National
Institute of Malaria
Research, India
Dr Thomas Wellems
Chief, Laboratory of
Malaria and Vector
Research, National
Institute of Allergy and
Infectious Diseases, USA
Dr Matthew Wyvratt
Senior Vice-President,
Drug Discovery, Motif
BioSciences, Inc., USA
Access & Product Management Advisory Committee (APMAC)
Prof. Christian
Lengeler, Chairman of
MMV APMAC; Head,
Health Interventions Unit,
Swiss Tropical and Public
Health Institute,
Switzerland
Dr Neena Valecha
Vice-Chairman of MMV
APMAC; Director, National
Institute of Malaria
Research, India
Ms Valentina Buj
Health Specialist (Malaria
Partnerships), UNICEF,
USA
Dr Elizabeth Chizema
Director of Disease
Control, Surveillance
and Research, Ministry
of Health, Zambia
Dr Graciela Diap
Associate Staff of DNDi
and FACT Medical
Coordinator, Spain
Dr Alexander Dodoo
Director at WHO Collabo-
rating Centre for Advocacy
and Training in Pharmaco-
vigilance, Ghana
Dr Gunther Faber
Chairman, One Family
Health, UK
Dr Douglas Lungu
Mzuzu Central Hospital,
Malawi
Dr David McGibney
Pharmaceutical
Research and Develop-
ment Expert; Consultant
Pharmaceutical Physician,
UK
Prof. Ric Price
Associative Professor,
Menzies School of Health
Research, Darwin,
Australia
Dr Melanie Renshaw
Chief Technical Advisor,
ALMA, Kenya
Dr Claude Emile
Rwagacondo
Coordinator of West
and Central Africa Roll
Back Malaria Network,
Senegal
Dr GS Sonal
Additional Director and
Head of Malaria Division
of the National Vector
Borne Disease Control
Programme, India
Dr Richard Steketee
Science Director, Malaria
Control Program and
MACEPA, PATH, USA
Prof. Andy Stergachis
Professor of
Epidemiology and Global
Health, Adjunct
Professor of Pharmacy
and Health Services,
Director of the Global
Medicines Program,
University of Washington,
USA
Dr Brenda Waning
Chief, Global Drug Facility,
Stop TB Partnership,
Switzerland
Global Safety Board
Dr Trevor Gibbs
Co-Chairman of MMV
Global Safety Board;
Senior Vice-President,
Pharmacovigilance &
Medical Governance,
GlaxoSmithKline, UK
Dr Stephan Duparc
Co-Chairman of MMV
Global Safety Board; Chief
Medical Officer, MMV,
Switzerland
Sir Colin Dollery,
Senior Consultant,
GlaxoSmithKline Research
and Development, UK
Dr Neil Garbet
Independent Consultant
Pharma ceutical Physician
and Consulting Partner to
Kinapse Ltd, UK
Dr David McGibney
Pharmaceutical Research
and Development Expert;
Consultant Pharmaceutical
Physician, UK
Prof. Tim Hammond
Preclinical Safety
Consulting Ltd, UK
7 | Behind the scenes
58
Nada Abla Geiser
Senior Drug Metabolism & Pharmacokinetics
(DMPK) Scientist, Drug Discovery
Marc Adamy
Director, Product Development
Samantha Akakpo
Regulatory Safety Advisor
Nicole Andenmatten
Translational Medicine Scientist
Nada Araeipour
Associate Director, Business Development
Adam Aspinall
Director, Product Strategy & Management
Muriel Aubert
Project Coordinator, Translational Medicine
Jaya Banerji
Director, Advocacy & Communications
Chris Barker
Travel Coordinator
Lidiya Bebrevska
Associate Director, Translational Medicine
Keeva Beke
Legal Coordinator
Soazig Bertrand
Finance Officer
Susan Bianchi
Business Development Assistant
Sophie Biguenet
Medical Director
Benjamin Blasco
Research Scientist, Drug Discovery
Grégory Bonnaud
Finance Director
Isabelle Borghini-Fuhrer
Director, Product Development
Jeremy Burrows
Vice-President, Head of Drug Discovery
Andrea Buscaglia
Chief Financial Officer
Brice Campo
Director, Drug Discovery
Stephan Chalon
Medical Director
John Clare
IT Manager
Marion Colombani
Senior Legal Officer
Maud Couturier
Strategic Meetings Officer
Gelavizh Daghigh
Office Administrator
Helen Demarest
Associate Director, Clinical Operations
Heidi Divecha
R&D Administrative Officer
Christina do Paço
External Relations Officer
Matthew Doherty
Manager, Donor & Stakeholder Relations
Cristina Donini
Director, Translational Medicine
Celia Doudou
Legal Officer
Angelique Doy
Drug Discovery Coordinator
James Duffy
Associate Director, Drug Discovery
Stephan Duparc
Chief Medical Officer
Mélanie Dupuy
Junior Financial Controller
Myriam El Gaaloul
Senior Clinical Scientist
Fanny Escudié
Project Coordinator, Drug Discovery
Sylvie Fonteilles-Drabek
Executive Vice-President, Head of Legal
Nathalie Gobeau
Associate Director, Pharmacometrics,
Translational Medicine
Petra Grand
External Relations Coordinator
Joan Herbert
Director, Business Development
Heike Huegel-Koerpert
Project Manager, Translational Medicine
Pierre Hugo
Senior Director, Access
& Product Management
MMV staffMarch 2016
59
George Jagoe
Executive Vice-President, Access
& Product Management
Sandra Johnson
Associate Director, Outsourcing
& Relationship Management
Alexis Kamdjou
Country & Procurement Liaison Manager
Franziska Karyabwite
Vice-President, Head of Human Resources
Wiweka Kaszubska
Vice-President, Head of
Product Development
Elizabeth Kernen
Administrative Assistant
Eun Jin Ko
Finance Intern
Benoit Laleu
Research Scientist, Drug Discovery
Didier Leroy
Director, Drug Discovery
Andrea Lucard
Executive Vice-President,
Head of External Relations
Adrienne MacDonald
Online Communications Officer
Fiona Macintyre
Director, Clinical Development
Simona Mag Valigova
Legal Officer
Maud Majeres Lugand
Research and Projects Manager,
Access & Product Management
Neil McCarthy
Vice-President, Head of External Relations
Jörg Möhrle
Vice-President, Head of
Translational Medicine
Alessandra Monaco
Translational Medicine Scientist
Alice Neequaye
Quality Officer & Archivist
Peter Okeyo
External Relations Intern
Gabrielle Pena
Archiving Assistant
Elise Penarrieta
Discovery Intern
Alicja Poczatenko
Legal Officer
Elizabeth Poll
Communications Manager
Hanu Ramachandruni
Senior Director, Technical
Product Development
Anya Ramalho
Executive Vice-President,
Business Development
David Reddy
Chief Executive Officer (CEO)
Wendy Redford
Human Resources Generalist
Véronique Reusse
Human Resources Recruitment Partner
Emilie Rossignol
Project Manager, Translational Medicine
Mélanie Rouillier
Project Coordinator, Drug Discovery
Thomas Rückle
Director, Translational Medicine
Anouchka Smits Bayala
Product Development Coordinator
Tareq Sunderji
Legal Administrative Officer
Yuko Takase
Finance Officer
André-Marie Tchouatieu
Associate Director, Access
& Product Management
Kim Van der Weijde
Access Intern
Helen Weir
Personal Assistant to the CEO
Timothy Wells
Chief Scientific Officer
Paul Willis
Director, Drug Discovery
Antonia Wolff
Project Coordinator,
Translational Medicine
Defeating Malaria Together
MMV is grateful for the support in 2015 from the following institutional donors:
MMV is also grateful for the support received from private individuals.
International Centre Cointrin
Route de Pré-Bois 20, PO Box 1826
1215 Geneva 15, Switzerland
Tel. +41 22 555 03 00
Fax +41 22 555 03 69
www.mmv.org
Editors Elizabeth Poll & Jaya Banerji, MMV
Designer ComStone - Pierre Chassany, Geneva, Switzerland
Printer Atar Roto Presse SA, Geneva, Switzerland
Lithograph Catherine Vogt, Carouge, Switzerland
Photographs BMC St Jude (p. 13), Pierre Chassany (p. 53), Samuel Choudhury* (pp. 20 & 21), Carl Craft/MMV (p. 2), Pearl Gan/Oxford
University Centre Research Unit (OURCRU)/Eijkman Oxford University Research Unit (EOCRU)/The Wellcome Trust
(Covers front and back), Pierre Hugo/MMV (p. 35), Muhammed Joof (p. 38), Benjamin Moldenhauer (p. 29), Elizabeth
Poll/MMV (pp. 15 & 19), Jetsumon Sattabongkot Prachumsri (p. 28), Damien Schumann (pp. 14 & 22), Nicolas
Spuhler (p. 58), Kim van der Weijde/MMV (p. 16), W Studios, New York (p. 56) and Anna Wang/MMV (pp. 5, 11 & 41).
Small portrait photos provided by interviewees.
* Photograph from Swiss Malaria Group photo contest 2013 ‘Malaria: the BIG Picture’
National Institutes
of Health (NIH/NIAID)