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ANNUAL
REPORT
2012
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
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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
© May 2013 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.
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Medicines for Malaria Venture (MMV) is recognized as the leading product development partnership in the field of antimalarial drug research and development. It was established as a foundation in 1999 and registered in Switzerland.
MMV’s mission is to reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of 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.
Message from the Chairman and CEO 5
Accelerating to zero: the quest for eradication
Key achievements 8
Message from Dr Fatoumata Nafo-Traoré, RBM 10
Defeating malaria once and for ALL
Better medicines for uncomplicated malaria 12
Using evidence to guide best practice 12
Building in-country capability to advance access 14
Beyond ACTs 15
New models to accelerate drug development 16
MMV portfolio – 4th quarter 2012 17
Medicines for vulnerable populations 18
Developing medicines for children and infants 18
Severe malaria: saving lives, changing practice 20
Protecting vulnerable patients 22
Medicines for malaria elimination/eradication 24
Blocking transmission 24
Stopping the relapse 26
OSDD powering the pipeline and changing the paradigm 28
Malaria Box & Top 10 MMV publications of 2012 29
MMV Project of the Year 2012: MMV390048 – boosting African research 30
Financial view 32
Behind the scenes 48
Malaria parasite lifecycle – targeting eradication
MMV portfolio – 4th quarter 2012
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Poster
Contents
44
5
“
1Accelerating to zero:
the quest for eradication
In 2012, MMV was proud to bring
forward the fourth drug since its
inception. Pyramax® was devel-
oped in partnership with Shin Poong
and received positive scientific opinion
from the European Medicines Agency in
February 2012. MMV’s co-developed
medicines are serving the needs of
vulnerable people and helping us accel-
erate to near-zero preventable deaths
from malaria.
MMV’s 13 years of endeavour have pro-
duced more than just medicines. We
have developed a vibrant network of
committed partners, a pipeline of pro-
mising new compounds with the poten-
tial to become new medicines, and data
and platforms to help us develop them
more effectively.
Thanks to the scale-up of preventive
measures and improved access to ef-
fective medicines, the malaria landscape
is changing. Mortality and morbidity are
decreasing.1 Yet signs of resistance to
artemisinin2 – the cornerstone of current
antimalarial therapy – are increasing,
albeit still limited to one region of south-
east Asia. These signs are a stark re-
minder that our gains are fragile and the
need for next-generation medicines is
growing more urgent.
To accelerate the development of new
treatments from bench to bedside,
2012 was a year of transition to smarter,
leaner and faster processes. It was also
a year in which MMV made significant
progress in helping to get newly ap-
proved medicines further, to cure more
people faster.
Developing new medicines faster
New tools, such as mathematical model-
ling and MMV’s human clinical pha rma-
cology platform (page 16), allow us to
understand better whether a compound
will work in humans, and what dose
is optimal; to make choices that are
more informed; and achieve more for
less. These tools have already helped
us bring down the cost of early proof-
of-concept studies from USD 4.5
million to USD 3 million, and we estimate
will shave approximately 2 years off
the development process.
Message from the Chairman and CEO
Dr David Reddy
MMV’s CEO
Mr Ray Chambers
Chairman of the Board
If you want to go fast, go alone.
If you want to go far, go together.”African proverb
1 World Health Organization. “World Malaria Report 2012.” http://www.who.int/malaria/publications/world_malaria_report_2012/en/
2 Carrara VI et al. “Malaria Burden and Artemisinin Resistance in the Mobile and Migrant Population on the Thai–Myanmar Border, 1999 –2011: An Observational Study.” PLoS Med 10(3): e1001398 (2013).
1 | Message from the Chairman and CEO
6
Discovering new compounds together
The extensive screening campaign of
six million compounds, conducted by
MMV and partners between 2008 and
2012, has provided a huge pool of
high-quality chemical starting points for
new antimalarial projects and raised the
bar for project selection. We are in a po-
sition to defer the development of some
molecules and select the most promis-
ing ones that are best matched to our
target product profiles for eradication.
Pooling the best scientific minds to
progress promising compounds, we
launched an exciting new initiative, the
Open Source Drug Discovery (OSDD)
programme (page 28). The concept is
simple and internet-based: researchers
post their study results and challenges
online, and experts from across the
world openly share solutions and drive
progress. The OSDD programme com-
bined with the sharing of 103 copies of
MMV’s Malaria Box in its first year, has
shown that we can start to change the
paradigm and conduct research in a
more open format.
We are also actively building research
and development (R&D) capacity in en-
demic countries. Working with scientists
in Africa, Asia and South America, we
have established cutting-edge research
platforms and models to identify and
develop new transmission-blocking and
relapse-preventing treatments (pages
24–27). This commitment will continue
into 2013 and beyond.
Getting new medicines farther
In 2011 and 2012, two new medicines,
Eurartesim® (dihydroartemisinin-
piperaquine developed with Sigma-Tau)
and Pyramax (pyronaridine-artesunate
with Shin Poong), were approved by
stringent regulatory authorities. A great-
er choice of treatments could help
slow down the development of resis-
tance to artemisinin derivatives and
partner drugs.5 In 2012, Eurartesim was
deliver ed to Cambodia, the epicentre
of emerg ing resistance, where it is the
first-line treatment for malaria.
In the space of just 2 years, an esti-
mated 40,000–50,000 additional lives
were saved thanks to the delivery of six
million vials of Guilin’s MMV-supported
Artesun® (injectable artesunate) for the
treatment of severe malaria.6
MMV and Novartis have continued to
fulfill the promise to make better med-
icines available for children. By the
end of 2012, more than 171 million
treatments of Coartem® Dispersible
(artemether-lumefantrine) had been
delivered to 35 countries. The success
of this child-friendly treatment proves
that formulations targeted at specific
populations can make a dramatic differ-
ence; and underscores the importance
of further investment and commitment
to meeting the needs of other groups,
such as pregnant mothers, infants and
newborns.
The endoperoxide, OZ439, has just
completed Phase IIa trials and interac-
tion studies with partner drugs have
been initiated. Meanwhile, KAE609,
discovered by a research consortium3
with funding from the Wellcome Trust
and MMV, is being progressed by
Novartis. These two molecules could
become part of the next-generation
medicines to cure malaria in a single
dose and revolutionize the treatment
landscape (page 15).
Tafenoquine for radical cure4 of relapsing
malaria is currently in Phase IIb of clinical
development with GlaxoSmithKline and
could also be a one-dose cure – a huge
improvement on the 14-day course that
is the current standard-of-care (page
26). This, added to piperaquine, would
be the beginning of an arsenal of tools
that could eventually eliminate malaria,
including asymptomatic malaria, from
an increasing number of countries.
With Pfizer, we are developing a new
preventive treatment for pregnant wo-
men (azithromycin-chloroquine) that will
also help to cure other infections (page
22). Combining two medicines that are
known to be well tolerated in this vulner-
able group means that we can bring a
safe and effective combination forward
quickly. With Guilin, we are also explor-
ing new ways to expand the reach of
seasonal malaria chemoprevention for
children (sulfadoxine-pyrimethamine +
amodiaquine) (page 23).
7
“Access is not just about delivering
new, effective treatments to disease-
endemic countries; it is also about help-
ing to ensure appropriate structures are
in place so medicines reach patients
who need them most. Our CAPSS
Plus programme in Uganda (page 14)
demonstrated the value of engaging
private-sector drug shopkeepers to
help improve their ability to diagnose
and treat malaria and other childhood
illnesses7 appropriately. In Tanzania,
the SMS for Life programme (page 14)
continued to provide weekly data feeds
regarding the availability of national first-
line treatments in over 5,000 public
health facilities. After nearly 2 years of
support for the scale-up and evaluation
of the programme, MMV was proud
to hand over the management to the
Tanzanian Government in early 2013.
The quest for elimination and eradication
With a focused strategy in place, and
new tools and platforms to enable us to
be even more rigorous in our portfolio
management, in 2012 we were able to
accelerate our R&D and access efforts
considerably. As a result and thanks to
the continued support of our partners
and donors, MMV made significant
headway in the quest for malaria elim-
ination and eradication. The more
partners we work with, the more we
achieve. MMV’s highly skilled and
committed staff are now working with
over 290 public and private research
partners in 50 countries, and the
numbers are growing.
As an organization, we are going faster
and further than ever before. If we can
maintain current momentum and fund-
ing levels, we stand a strong chance of
making the greatest possible impact on
malaria in the shortest possible time.
With less than 1,000 days to go, the
race is on to achieve the Millennium
Development Goals (MDGs). Preventing
deaths from malaria alone would take
us one fifth of the way towards MDG4 to
reduce child mortality.8 Now is the time
to pool all possible resources and accel-
erate to near-zero preventable deaths
from malaria and our ultimate goal of
malaria eradication.
Thanks to our partners
and donors, MMV made
significant headway in
the quest for malaria
elimination and
eradication.”
3 The research consortium comprised Novartis, Swiss Tropical and Public Health Institute and Biomedical Primate Research Institute, the Netherlands.
4 Radical cure of P. vivax malaria involves eliminating all forms of the parasite from a patient including hypnozoites to cure the disease and prevent its relapse.
5 Boni MF, Smith DL, Laxminarayan R. “Benefits of using multiple first-line therapies against malaria.” Proc Natl Acad Sci USA. 105(37):14216-21 (2008).
6 Additional lives saved, compared to patients treated with quinine: Estimates based on drug distribution data since WHO Prequalification (2011 and 2012) and survival rates from AQUAMAT (1) and SEAQUAMAT (2) trials: (1) Dondorp AM et al. Lancet, 376(9753): 1647-57 (2010); (2) Dondorp AM et al. Lancet, 366(9487): 717-25 (2005).
7 Childhood illnesses such as pneumonia and diarrhoea.8 Millennium Development Goal 4 is to reduce by two
thirds, between 1990 and 2015, the under-5 mortality rate. The mortality figure in 1990 was 12 million annual deaths; we now need to save another 4.4 million lives to reach the goal. Current mortality figures for malaria are between 610,000-971,000, 86% of which are children under 5, according to WHO.
8
million treatments ofchild-friendlyCoartem®
Dispersible
171
( a r t e m e t h e r - l u m a f a n t r i n e ,
co-developed with Novart is) distributed to 35 countries since launch in 2009.
million
vials ofArtesun®
6(Guilin Pharmaceutical’s MMV-
supported injectable artesunate)
for severe malaria deliver-ed since 2010 – saving approximately 40,000 -50,000 additional lives compared to treatment with quinine.
3 stamps of approval for Pyramax®
( p y r o n a r i d i n e - a r t e s u n a t e ,
co-developed with Shin Poong) – the first artemisinin-based combination therapy with clinical data and a regis-tered indication for treating P. falciparum and P. vivax blood-stage malaria:
Korea Food and Drug Administration, August 2011
scientific opinion from European Medicines Agency under Article 58, February 2012
Organization’s list of prequalified medicines, May 2012
400,000treatments of
(dihydroartemisinin-piperaquine;
co-developed with Sigma-Tau) shipped as first-line drug to Cambodia, one of the countries leading the fight to contain artemisinin-resistant strains of malaria. It is now also registered for use in Ghana, Tanzania, Burkina Faso and through-out Europe.
Eurartesim®
medicines in clinicaldevelopment
7targeting malaria eradica-tion by aiming to stop re-lapse, block transmission, cure drug-resistant strains and serve the needs of as many patients as possible.
new
9
CAPSS
Plus programmeshows increasing private- sector access to malaria diagnostics alongside med-icines can improve overall case management of fever.
malaria researchers
12received an Ian Bathurst
to enable them to partici-pate and exchange ideas with experts at Keystone’s Malaria Symposia, January 2013.
Malaria Boxes 103
dispatched to 26 countries in 2012 to catalyze malaria and neglected disease drug research.
pharma
giants
4(GlaxoSmithKline, Novartis, AstraZeneca and Sanofi) brought together by MMV to discuss a shared anti-malarial drug discovery strategy.
models2to streamline and expedite development of next-generation antimalarials:
Challenge Model: tests drug candidates in healthy individuals infected with malariaPharmacokinetic and Pharmacodynamic Modelling: speeds up development by using mathematical modelling to predict link between drug concentration and efficacy
new
Direct and in-kind support from our pharma partners more than doubles the value of each donor dollar
=1 2.50USD USD
Keyachievements
“10
Malaria has caused the tragic
loss of countless lives and
robbed many households
and communities across the world of
their livelihoods, locking them in a vi-
cious cycle of illness and poverty. It has
impeded social and economic develop-
ment, especially in Africa where 90%
of the global malaria burden weighs
heavily. Today, thanks to increased in-
vestment from governments and the
philanthropic sector, and the concerted
efforts of the global health community,
that picture is beginning to change.
I joined the Roll Back Malaria Part-
nership as Executive Director in 2012,
after many years working across Africa
for the World Health Organization
and other institutions and agencies.
I witnessed tremendous progress in
malaria control all over the continent.
Pregnant women and children, the
most vulnerable members of society,
now have greater access to life-saving
malaria interventions such as effective
treatments and insecticide-treated
nets. In Ethiopia, for example, greater
numbers of people are receiving
treatment for uncomplicated and
severe malaria in the right place at the
right time, with the support and care of
community health workers.
Knowing that help and safe treatments
are at hand and will save a child’s
life gives hope to all parents and
communities, but anticipating that,
one day, malaria could be eliminated
gives hope to an entire continent for
a future of growth and opportunity.
Spearheaded by Medicines for Malaria
Venture (MMV), the search for new tools
to defeat malaria, for compounds to
defy parasite resistance, for single-dose
treatments that beat non-compliance,
and for drugs that could block
transmission from person-to-person, is
crucial in today’s battle against malaria.
All these interventions are critical on the
pathway to zero deaths from this age-
old disease, each bringing us closer
to elimination and, one day, to malaria
eradication.
As a doctor and former minister of
health in my home country of Mali,
I experienced the pressure put on
governments to meet the changing
health needs of populations, and the
scramble to find alternatives when drug
resistance had made our most effective
malaria medicine ineffective. Product
development partnerships like MMV
work hard to alleviate the burden of
diseases such as malaria, by harnessing
the expertise and knowledge of both the
2 Defeating malaria once
and for ALL
... anticipating that one
day, malaria could be
eliminated gives hope
to an entire continent
for a future of growth
and opportunity.”
Dr Fatoumata Nafo-TraoréExecutive Director of the Roll Back Malaria
Partnership
11
11
“If MMV didn’t exist,
we would have to
invent it.”
private and public sectors to find the
most efficient, effective and affordable
solutions. We cannot do without them.
Nor can we do without the operational
research that they deploy, to show far
more effectively than current surveys
how communities, families and
especially mothers can access and use
these interventions. It is unacceptable
to continue to see a child die every
60 seconds of a perfectly curable
disease. It is also unacceptable that
with the communication technologies
available to almost everyone today,
drugs and rapid diagnostic tests are still
not reaching the communities where
they are needed and stock-outs still
occur. Improving systems, improving
delivery and improving acceptance by
communities is as critical as developing
the new tools we so desperately need.
MMV has transformed the product
landscape for malaria and created
hope. “Si MMV n’existait pas, il aurait
fallu l’inventer” (If MMV didn’t exist, we
would have to invent it).
As Executive Director of the Roll Back
Malaria Partnership I urge the malaria
community to make endemic countries
and communities absolutely central to
our efforts and to focus more acutely
on hard-to-reach populations, including
the poorest sectors of society. This
focus requires much more work,
more investment and definitely more
knowledge and understanding, but it
is the only way to reach our ambitious
goals of elimination and eradication.
Over the last decade, we have seen
that the fight against malaria has been
one of our best investments in global
health to date. Malaria was neglected
in the past, but no more. I hope that in
the coming years we will see that fight
continue, leading to universal coverage
with the best tools and approaches so
that the poor are lifted out of poverty
and have the opportunities they
deserve. It is clear that if we wish to
defeat malaria, we must defeat it once
and for all – leaving no one behind.
12
Using evidence to guide best practice
3 Better medicines for uncomplicated malaria
Cambodia was the first country to reg-
ister Eurartesim for use. By the begin-
ning of 2013, approximately 400,000
treatments had been delivered. The
medicine is now being used to treat
patients in one of the key countries
working to contain the spread of drug-
resistant malaria in south-east Asia.
Eurartesim has since been registered
for use in Ghana, Tanzania and Bur-
kina Faso as well as across Europe.
These first Africa registrations for
the medicine mean it can now be used
in the INESS2 programme to monitor its
real-life safety and effectiveness.
Pyramax, developed in partnership
with Shin Poong, received a positive
scientific opinion from the European
Medicines Agency in February 2012.
It is the first antimalarial to follow the
Article 583 route of approval and the
first to be endorsed for the treatment
of both major species of parasite
to infect humans P. falciparum and
P. vivax. The drug is now being reviewed
for registration in Vietnam, Myanmar
and Thailand. In south-east Asia, it
will be an important additional tool for
WHO’s artemisinin resistance contain-
ment strategy.
These two new medicines add to the
choice of antimalarials, enabling disease-
endemic countries to adapt control
strategies to their specific needs.
Mathematical modelling studies sug-
gest that using multiple first-line ACTs
could yield better clinical out comes than
deploying a single ACT nationwide par-
ticularly when drug resistance or treat-
ment failures emerge.4,5 The key now is
to gather the evidence to guide optimal
and widespread use of new ACTs like
Eurartesim and Pyramax.
1 Valecha N at al. “An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia.” PLoS One. 5(7):e11880 (2010).
2 INESS: INDEPTH Effectiveness and Safety Studies of Anti-malarial Drugs in Africa.
3 Article 58 is the regulatory route by which the EMA provides a scientific opinion, in cooperation with the World Health Organization (WHO), for the evaluation of medicinal products intended exclusively for markets outside the European Community.
4 Boni MF, Smith DL, Laxminarayan R. “Benefits of using multiple first-line therapies against malaria.” Proc Natl Acad Sci USA. 105(37):14216-21 (2008).
5 Smith DL et al. “Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty.” Malar J. 9:217 (2010).
Artemisinin-based combination
therapies (ACTs) are today’s
gold standard antimalarials.
Eurartesim® (dihydroartemisinin-pip-
eraquine) and Pyramax® (pyronaridine-
artesunate) are the latest ACTs to
emerge from MMV’s pipeline.
Eurartesim, developed in partner-
ship with Sigma-Tau, provides longer
protection against re-infection1 and
could therefore help to decrease the
incidence of malaria, particularly in
high-transmission areas. It received
approval from the European Medicines
Agency in 2011 (for more details
see page 18).
“...multiple first-line
ACTs could yield better
clinical outcomes than
deploying a single ACT...”
13
How are mathematical models
helping to inform National Malaria
Control Programmes about
the tools best suited to their
countries?
To date, they have mostly been used in
a malaria research context and to advise
at a global level, but their use is grow-
ing. There is increasing interest from
National Malaria Control Programmes
in using models, especially as they see
budgets being cut and need to devise
cost-effective strategies using available
interventions: bednets, indoor spraying,
chemoprophylaxis or a vaccine when it
comes. A combination of models and
health economics can guide rational
use of these interventions in different
settings.
What can the models tell us
about the use of medicines in
blocking transmission?
There are two key properties of an anti-
malarial: first, how quickly it clears para-
sites – treating the patient and preventing
transmission – and second, how long the
drug remains in the body, protecting it
from further infection – an issue that is very
important in high-transmission settings.
In these settings, a drug like Eurartesim
would be useful owing to its long half-life.
In a low-transmission setting, however,
just a few infections sustain transmission
so the key is to cure them quickly and
eliminate the reservoir.
This suggests a ‘one drug fits all’ ap-
proach is not the best, and gives an
indication of the kind of drugs that
would be more appropriate in different
settings. Ideally, we need a drug with
fast gametocytocidal action to prevent
transmission and long activity to provide
post-treatment protection.
Prof. Azra C Ghani
Imperial College London, UK, explains
how these models are being used
today.
A medicine’s performance in rou-
tine practice can differ from its
performance in carefully con-
trolled clinical trials. Trials recruit thou-
sands of patients who, due to strict
inclusion criteria, do not always reflect
the physiological profiles of the ultimate
treatment population. To help guide
best treatment practice in differing pop-
ulations, it is important to continue to
gather evidence post-approval.
Theoretical assumptions can initially
be made using mathematical models.
Models and malaria have gone hand-
in-hand since the early 20th century,
when Sir Ronald Ross pioneered their
use for infec tious diseases. They were
later ex plo red to help develop the first
eradication strategy in the 1950s.
Theory aside, we need to under-
stand the reality through trials in
real-life settings, such as INESS.2
In addition, with the support of the Euro-
pean & Developing Countries Clinical
Trials Partnership (EDCTP) led by Prof.
Charles Mgone, MMV is working with
the West African Network for Clinical
Trials of Antimalarial Drugs (WANECAM)
to conduct some longitudinal studies of
Eurartesim and Pyramax. This research
is particularly important for Pyramax as
elevations in liver enzymes were noted
in a small number of subjects following
treatment with the medicine. Repeat
dose findings to date are reassuring (no
differences in the liver enzymes between
first and subsequent dosing) and have
enabled children as young as 6 months
to be included in the study.
Prof. Fred Binka
Principal Investigator of INESS2
explains how it will gather data
on the safety and effectiveness of
these new ACTs.
How is INESS helping to gather
evidence to improve malaria
treatment?
Using census data collected in Ghana,
Burkina Faso, Mozambique and Tanza-
nia as a baseline, we gather information
on malaria patients directly from health-
care facilities. We look at how easy it is
to access health care, how long it takes
to get treatment, which treatment they
receive and their compliance to the reg-
imen. We then follow-up in their homes
to see if there are any adverse reactions.
What we are really looking at is not the
effectiveness of the drug alone, but the
effectiveness of the system to deliver
the drugs as well, to find out where the
pitfalls lie.
What has the study revealed
so far? What do you expect to
discover in terms of the different
attributes of available ACTs?
So far, we have looked at two ACTs:
artemether-lumefantrine (AL) and
artesunate-amodiaquine (AS-AQ). The
differences we have seen in terms of
effect iveness tend to reflect differences
in health systems rather than in the
drugs. When we start to look at Eurar-
tesim, as an ACT that provides longer
post-treatment prophylaxis, we might
start to see differences. It will be inter-
esting to see what these are.
“We hope the results of WANECAM
will support the use of Pyramax in
sub-Saharan Africa, where children
experience several episodes of malaria.
The long-term safety of Eurartesim in full
field conditions will also be assessed.”Prof. Abdoulaye Djimdé, Chief of Laboratory, Malaria Research and Training Center, University of Bamako, Mali, leads the WANECAM study.
3 | Better medicines for uncomplicated malaria
14
Preventing stock-outs
Stock-outs of antimalarial medicines in
health-care facilities across Africa are
a widespread problem – and one that
can cause needless deaths. SMS for
Life uses widely available mobile phone,
internet and Google mapping technolo-
gies to monitor antimalarial stock levels
at health-care facilities to help prevent
stock-outs.
The programme was initiated in 2009
by Novartis in collaboration with multiple
partners1 and piloted across 128 health-
care facilities in Tanzania. From February
2011, MMV and the Swiss Agency for
Development Cooperation collaborated
with the Ministry of Health and Social
Welfare Tanzania (MoHSW), Population
Services International and Novartis to
scale-up the programme nationwide –
covering all 5,099 frontline health-care
facilities in the country.
The system may eventually be used to
report on other essential medicines,
thereby helping to improve overall phar-
maceutical supply chain management.
With the national scale-up complete,
lead responsibility for the continuation of
the project was transferred to the Tan-
zanian Government in January 2013.
MMV has now commissioned an inde-
pendent evaluation of the SMS for
Life scale-up experience in Tanzania,
to assist and inform the MoHSW and
governments of other countries wishing
to undertake similar programmes.
Expanding correct case management in the private sector
Inappropriate use of antimalarials can
lead to poor treatment outcomes and
contribute to the development of arte-
misinin resistance. Attempting to avert
this, the World Health Organization is
calling for intensified efforts to ensure
confirmatory diagnosis before patients
are treated with antimalarial medicines.
This work is part of WHO’s T3 initiative –
Test-Treat-Track.2
In support of this call, in 2011–2012
MMV collaborated with Makerere Uni-
versity in Uganda and the Karolinska
Institutet, Sweden, to develop the
CAPSS3 Plus programme. CAPSS Plus
demonstrated the feasibility and bene-
fit of training private drug shopkeepers
in rural Uganda to use rapid diagnostic
tests to diagnose malaria and dispense
ACTs as necessary.
In the event of a negative malaria test,
shopkeepers were also trained to
identify basic childhood illnesses (in-
cluding respiratory infections and diar-
rhoea-related dehydration) and provide
appropriate medicines. This initiative
highlights how integrated treatment
approaches that include the use of diag-
nostics, can improve patient outcomes
in private-sector settings, and reduce
inappropriate use of vital medicines.
Building in-country capability to advance access
1 The Tanzanian Government, the Roll Back Malaria Partnership, Vodafone and IBM.
2 World Health Organization. “Test, Treat, Track: Scaling up diagnostic testing, treatment and surveillance for malaria” (2012): www.who.int/malaria/publications/atoz/test_treat_track_brochure.pdf
3 CAPSS: Consortium for ACT Private Sector Subsidy demonstrated that making ACTs affordable can drive their uptake and availability and displace inferior treatments.
15
Beyond ACTs
Artemisinin-based combination
therapies (ACTs) are the main-
stay of malaria treatment to-
day, yet history tells us they will not
last forever. The first signs of possible
artemisinin resistance were identified
in south-east Asia more than 5 years
ago.1,2 This, coupled with the evidence
of the emergence of resistance to some
partner drugs in recent years, has led to
concerns of an inevitable decline in effi-
cacy of commonly used combinations.3
While WHO containment efforts are
underway, we must be prepared with
alternatives. One of MMV’s key areas
of focus is ensuring next-generation
antimalarials are brought to the fore as
quickly as possible.
The goal is to develop novel medicines
that are not only safe and effective but
also easier to take and administer. 2012
saw the accelerated progress of the
endoperoxide, OZ439. Meanwhile, the
spiroindolone, KAE609, demonstrated
efficacy in patients. Both compounds
show potential to become single-
dose cures and have transmission-
blocking ability. In addition, KAE609,
being progressed by Novartis, is the first
antimalarial with a new mechanism of
action to enter clinical development in
the last 20 years.
These two molecules are the most
advanced compounds in MMV’s
portfolio to form the building blocks of a
first-generation Single Exposure Radical
Cure and Prophylaxis (SERCaP). The
challenge now is to determine if these
molecules can meet the impressive
clinical efficacy of a 3-day ACT, with a
shorter course of treatment. In parallel,
the research and development team
are studying the effects of OZ439 with
different partner drugs to identify the
best combination.
“A one-dose cure for malaria, with the same efficacy
as the current 3-day cure, would really make a
big difference on the ground; not only logistically,
in terms of transport, storage and availability, but
also in terms of guaranteeing the correct dose.
With a one-dose cure, I would rest assured that my
patients receive a complete cure right in front of
me. This is clearly important for the patient but
also to prevent drug resistance.”Dr Martin De Smet, Head of Médecins Sans Frontière’s Working Group on Malaria
OZ439
Phase IIb
Target indication: Acute uncomplicated
malaria
Advantages:
better compliance and effectiveness4
strains of malaria5
Project Leader: Dr Fiona Macintyre, MMV
OZ439/4-aminoquinoline development
partner: Sanofi
Discovery partners: University of
Nebraska Medical Center, USA; Monash
University, Australia; and Swiss Tropical
KAE609
Phase IIa
Target indication: Acute uncomplicated
malaria
Advantages:
better compliance and effectiveness6
5
strains of malaria7
Project Leader: Dr Thierry Diagana,
Novartis Institute for Tropical Diseases
MMV Project Director: Dr Jörg Möhrle
Development partner:
Discovery partners: Novartis Institute for
Tropical Diseases, Singapore; the
Wellcome Trust, UK; Swiss Tropical
Research Institute, the Netherlands;
and Genomics Institute of the Novartis
Research Foundation, USA
5 Delves M at al. “The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites.” Plos Med. 9(2):e1001169 (2012).
6 Rottmann M et al. “Spiroindolones, a potent compound class for the treatment of malaria.” Science. 329(5996):1175-80 (2010).
7 van Pelt-Koops JC et al. “The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.” Antimicrob Agents Chemother. 56(7):3544-8 (2012).
1 Noedl H et al. “Artemisinin Resistance in Cambodia 1 (ARC1) Study Consortium. Evidence of artemisinin-resistant malaria in western Cambodia.” N Engl J Med. 359(24):2619-20 (2008).
2 Fairhurst RM et al. “Artemisinin-Resistant Malaria: Research Challenges, Opportunities, and Public Health Implications.” Am J Trop Med Hyg. 87(2): 231–241 (2012).
3 Carrara VI et al. “Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai–Myanmar border, 1999 –2011: an observational study.” PLoS Med. 10(3): e1001398 (2013).
4 Moehrle JJ et al. “First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials.” Br J Clin Pharmacol. 75(2):524-37 (2013).
3 | Better medicines for uncomplicated malaria
16
Pharmacokinetics (PK):
what the body does to the drug,
which determines where and when
the drug will have its effect, for how
long and at what level of intensity.
Pharmacodynamics (PD):
what the drug does to the body, which
determines how the drug behaves
and exerts its therapeutic effect.
The pharmacokinetics (PK) and
pharmacodynamics (PD) of a
drug characterize how it works
in the body and determine what dose is
needed over what course of time. PK/
PD measures can vary depending on
the patients’ age, gender, ethnicity, diet
and the severity of their disease. So it is
critical to understand a drug’s PK/PD in
the target patient population to enable
its safe and effective use.
Typically, PK/PD data are collected
throughout the development process. In
the preclinical stage, data are collected
to predict drug activity in humans and
its effects against the parasite using
sophisticated model systems.1
Predictions are then
confirmed in clinical
trials and a cycle
of learning and
confirming begins
until the most ap-
propriate dose in
patients can be
determined.
Mark Baker
Associate Director, Translational
Medicine, MMV, and a clinical
pharmacologist, explains two inno-
vations that are enabling MMV to
accelerate the collection and use
of PK/PD data to speed the deve-
lopment of next-generation anti-
malarials.
What methods have been
employed at MMV to accelerate
the collection of this data?
In collaboration with the Queensland
Institute of Medical Research and Prof.
James McCarthy, we developed the
Challenge Model – a new approach
to testing candidate molecules in in-
dividuals with malaria, without putting
patients at risk.
Healthy volunteers are inoculated with
a small number of red blood cells in-
fected with P. falciparum malaria. We
closely monitor the level of parasitaemia
in their bloodstream using a highly sen-
sitive technique known as quantitative
Polymerase Chain Reaction (qPCR).
This technique enables us to ensure the
volunteers are never at risk. They are
then treated with the candidate drugs
and we use qPCR to characterize the
drug’s effects against the parasite.2
So far, the Challenge Model has been
validated by testing five already approv-
ed antimalarials. The data we generated
replicates what has already been found
in clinical trials of these medicines.
What approaches have been
adopted to streamline the use of
these data?
We have recently adopted a PK/PD
modelling approach. We take aggre-
gated raw data and determine rela-
tionships between concentration and
efficacy using the power of maths; we
can then make predictions about how
a compound will behave in humans.
Predictions can then be confirmed in
clinical trials, leading to a cycle of learn
and confirm. The approach is well-
established in other therapeutic areas.
All the knowledge and new data we can
now generate throughout the develop-
ment process, thanks to the Challenge
Model, for example, mean we can use
the approach in malaria too (Figure 1).
How will these approaches im-
prove the research and develop-
ment process at MMV?
Typically in R&D, medicines are trialled
first in healthy volunteers to help deter-
mine safety, before being testing in pa-
tients to determine if the experimental
medicine actually works (efficacy). The
Challenge Model can determine efficacy
at the same time as trials in volunteers
are initiated to determine safety.
Use of the Challenge Model also means
that when we come to trial a drug in
patients we can be more certain of the
optimal dose. The PK/PD model en-
sures all data collected – preclinical and
clinical – are used to the full, creating
a global view of the drug and parasite
interaction.
These approaches taken together mean
we require fewer patients in clinical
trials, and are able to generate more
data in less time at a lower cost (see
Table 1). By obtaining more data earlier,
we can make informed risk analysis and
improve portfolio management.
New models to accelerate drug development
1 Angulo-Barturen I et al. “A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes.” PLoS One. 3(5):e2252a (2008).
2 McCarthy JS et al. “A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs.” PLoS One. 6(8):e21914 (2011).
Table 1: Time and resources saved in
the development of OZ439 using PK/PD
modelling versus the classic approach
TIM
E
CO
NC
EN
TRATIO
N
EFFE
CTS
DOSE
CCCCCCCCCCCCCCO
CCCO
CO
CO
CO
COOO
NC
$
Fewerpatients
Faster development
Lower costs
New well-defined medicines
DATA
Broader applicationsR age
R gender
R ethnicity
OTHERS
C
O N F I R
M
LEARN
PK/PD
Classic
Dose per arm Time People
5
3
10
10
1.5 years
3 months
50
30
Figure 1
PK/PD modelling
17
MMV portfolio – 4th quarter 2012
1. Coartem Dispersible is in a Phase IV programme led by Novartis
2. MMV worked with Guilin to achieve WHO prequalification for this medicine
3. AS-AQ Winthrop: this DNDi and Sanofi product is in Phase IV trials with MMV
4. MMV is working with Guilin to achieve WHO prequalification for this medicine
Non-artemisinin-based therapy
Artemisinin-based therapy
Included in MMV portfolio post registration
Novartis Miniportfolio
Novartis 1 project
GSK Miniportfolio
SanofiMiniportfolio
GSK 4 projects
Sanofi Orthologue Leads
AstraZeneca Whole Cell Leads
Ferrer-GSKHeterocycles
Liverpool School of Trop Med/Univ. Liverpool 2 projects
AstraZeneca Miniportfolio
Univ.of SydneyOpen SourceDrug Discovery
Monash Univ.Kinases
Other projects 18 projects
Univ. of Cape TownAminopyridines
Univ. of DundeeHeterocycles
Other projects 4 projects
DSM265 (Univ. of Texas Southwestern/ Univ. of Washington/Monash Univ.)
GNF156 Novartis
KAE609 Novartis
MMV390048(Univ. of Cape Town)
ELQ-300 (Univ. of South Florida/Oregon Health & Science Univ.)
21A092 (Drexel Univ./ Univ. of Washington)
P218 DHFR (Biotec/Monash Univ./LondonSchool of Hygiene & Trop Med)
Azithromycin-chloroquine (AZ-CQ) Pfizer
Tafenoquine GSK
Pyramax® Paediatric(pyronaridine-artesunate)
Shin Poong/Univ. of Iowa
Coartem® Dispersible(artemether-lumefantrine)
Novartis 1
Artesunate for injection Guilin 2
Eurartesim®
(dihydroartemisinin-piperaquine)
Sigma-Tau
Pyramax®
(pyronaridine-artesunate)
Shin Poong/ Univ. of Iowa
AS-AQ Winthrop(artesunate-amodiaquine)
DNDi/Sanofi 3
St Jude/Rutgers Univ./Univ. of South FloridaDihydro-isoquinolones
Eurartesim®
Paediatric (dihydroartemisinin-piperaquine)
Sigma-Tau
OZ439 Sanofi(Monash Univ./ Univ. of Nebraska/Swiss TPH)
Research Translational science DevelopmentLead
generationLead
optimizationPreclinical Phase I Phase IIa Phase IIb/
Phase IIIRegistration Phase IV
3-day cure/artemisinin-based combination therapies
Single-dose cure
Severe malaria
Intermittent chemoprevention
Relapse prevention
Fast clearance (TCP1)
Long duration (TCP2)
Relapse prevention (TCP3a)
Transmission blocking (TCP3b)
Chemoprevention (TCP4)
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
Nauclea pobeguiniiUniv. of Antwerp
Argemone mexicanaAssociation Mali-Genève/Univ. of Geneva
TCP: Target Candidate Profile
TPP: Target Product Profile
*
GO
VE
RN
AN
CE
SP+AQ(sulfadoxine-pyrimethamine + amodiaquine)
Guilin 4
*
18
4 Medicines for vulnerable
populations
Developing medicines for children and infants
Eurartesim® (dihydroartemisinin-piperaquine)
Adult formulation approved by the
European Medicines Agency (EMA)
Registered in Europe, Cambodia,
Ghana, Tanzania and Burkina Faso
Adult indication: Acute uncomplicated
P. falciparum malaria in adults and
children weighing 5 kg or more
Paediatric formulation – development
status:
daily dosing over 3 days
Project Leader: Gianemilio Stern,
Sigma-Tau
Partners: Sigma-Tau Industrie
Farmaceutiche Riunite, Italy
MMV Project Director: Aleksandra
Misiorowska
Coartem® Dispersible (artemether-lumefantrine)
Approved by Swissmedic1 and
prequalified by WHO
Indication: Acute, uncomplicated
P. falciparum malaria in infants and
children weighing between 5–35 kg
Paediatric formulation – advantages:
sweet-tasting, dispersible formulation
accurate dosing for children
on widespread use of parent drug
Coartem®
Project Leader: Dr Heiner Grueninger,
Novartis
Partners:
MMV Project Sponsor: Dr Wiweka
Children under the age of 5
continue to be the main vic-
tims of malaria. Yet with the
exception of Coartem Dispersible,
developed by the MMV/Novartis
partnership, few antimalarial med-
icines have been developed with
children’s needs in mind. MMV aims
to address this imbalance. Child-
friendly formulations of the recently
approved Eurartesim and Pyramax
are under development and could be
submitted for regulatory approval as
early as 2014.
Although the needs of younger children
are being addressed, medicines are
still not approved for use in the small-
est infants – those under 5 kg. In part,
this has been driven by a perception
that infants gain immunity from their
mothers. However, preliminary results
of an epidemiological study funded
by MMV and Novartis indicate that
the burden might be greater than
expected.2 In parallel, the MMV/
Novartis partnership is working to de-
termine whether Coartem Dispersible
can be used safely in these vulnerable
patients.
1 Swiss Agency for Therapeutic Products
2 D’Alessandro U et al. “Malaria in infants aged less than six months - is it an area of unmet medical need?” Malar J. 11: 400 (2012).
® (pyronaridine-artesunate)
Adult formulation approved by the
(South) Korea Food and Drug Admin-
istration; positive scientific opinion
under EMA Article 58; added to WHO’s
list of prequalified medicines
Adult indication: Acute uncomplicated
P. falciparum and blood-stage P. vivax
malaria in adults and children weighing
20 kg or more, in areas of low transmission
with evidence of artemisinin resistance
Paediatric formulation – development
status:
once-daily dosing over 3 days
administration
Project Leader: Dr Isabelle Borghini-
Fuhrer, MMV
Partners:
Ltd., South Korea
19
Prof. Umberto D’Alessandro
Medical Research Council Unit,
in Gambia, tells us about the epi-
demiological study assessing the
burden of malaria in babies under
5 kg.
What has the epidemiological
study revealed so far?
The study is ongoing in Gambia, Benin
and Guinea, countries with different levels
of malaria endemicity. We have just com-
pleted a survey of malaria prevalence in
infants under 6 months, and in the same
house or nearby, in children 1–9 years old
and 10–15 years old.
In Gambia, the prevalence was higher
than expected: ~10% of infants and
older children were infected with malaria.
In Guinea, 30% of infants and 80% of
older children were infected. This was ex-
pected, as the transmission here is very
intense. The survey has only just finished
in Benin and we are currently processing
the samples.
Dr Linus Igwemezie
Head of the Novartis Malaria
Initiative, explains the MMV/
Novartis partnership’s success,
and the additional challenges it
aims to address.
Novartis and MMV have collabo-
rated since 2003. Why do you
think the collaboration works
so well?
I think the secret is our shared objective
to address the unmet medical needs
for malaria and our ability to harness
the complementary expertise from both
organ izations to meet these needs. We
work together and make joint decisions in
a very transparent and consultative way.
This has led to the successful launch
of Coartem Dispersible, and I am very
proud that since launch, Novartis has
been able to deliver more than 171
million Coartem Dispersible treatments
without profit to the public sector in 35
countries. MMV is also providing major
support on other projects such as SMS
for Life in Tanzania and to our research
for next-generation medicines.
How can we ensure Coartem
Dispersible reaches the children
that need it?
By making it affordable and available.
Affordability is really about making
sure there is funding to provide the
product – especially in the public sec-
tor. It also means having the product
available at an affordable price in the
private sector, as not all Africans get
their antimalarials through the public
sector. For Coartem Dispersible,
Novartis is committed to providing the
product without profit in the public sector.
We are also looking at ways to provide
the product at an affordable price in the
private sector.
To take availability a step further, with
support from MMV, we developed the
SMS for Life programme to monitor
stock levels at points-of-care and avoid
stock-outs (see page 14). The pro-
gramme has been rolled-out across
Tanzania and we are keen to launch
similar programmes that include other
medicines and diagnostic tests, in
Ghana, Kenya and Cameroon.
As noted by Prof. D’Alessandro,
there is a potential need for medi-
cines tailored to the requirements
of babies under 5 kg. How can this
be addressed?
Novartis and MMV have initiated a study
to look at the safety and pharmaco-
kinetics of Coartem Dispersible in infants
under 5 kg. It’s a difficult study to do,
owing to the vulnerable nature of this
patient group, but we are committed
to doing the work to expand the label.
Hopefully, a new medicine will not be
necessary, but we need evidence to
support this.
Overall, the prevalence of infection is higher
than anticipated and it’s unclear why. It is
important to note that the majority of these
children were healthy. They were asymp-
tomatic – i.e. they were carrying the para-
site with no symptoms. To understand the
morbidity and mortality, we have to wait for
the next phase of the study.
How are infants under 6 months
currently treated for malaria?
At the moment, some doctors use quinine
or other treatments. The real problem is
there is very little data, particularly on the
way an infant’s body responds to the drug
(pharmacokinetics) to guide the dose
of the medicine. When you have a sick
baby in front of you, you treat it with the
best treatment and dosage you can. Up
to now, the dosage has been the one for
older children, but infants may well meta-
bolize the drug differently and so the dose
might need to be adjusted.
4 | Medicines for vulnerable populations
20
In April 2011, in light of new evidence
demonstrating the superiority of
injectable artesunate over quinine
for the treatment of severe malaria in
children,1,2 WHO updated its Standard
Treatment Guidelines to recommend
injectable artesunate as the preferred
treatment option. Prior to this, in anti-
cipation of the recommendation, MMV
worked with Guilin Pharmaceutical to
enable them to become the first manu-
facturers of injectable artesunate to
obtain WHO prequalification in 2010.
This internationally recognized seal of
approval allows countries to procure this
essential medicine with donor funds, and
reach many more patients thus expanding
its impact.
Since prequalification, MMV and two
partners, the Clinton Health Access
Initiative (CHAI) and the Swiss Tropical
and Public Health Institute (Swiss TPH)
have been working to increase uptake
and use of injectable artesunate across
the malaria-endemic world, with a
particular focus on two of the highest
burden countries: Nigeria and the
Dem ocratic Republic of the Congo. In
addition, MMV and WHO have worked
with multiple stakeholders to help revise
and disseminate operations manuals,
policy briefings and training materials,
to ensure that decision-makers are fully
informed and health-care workers pro-
perly trained in the use of this important
life-saving medicine.
In July 2012, MMV, CHAI and the Na-
tional Malaria Control Programme in Ni-
geria launched a project to scale-up the
use of injectable artesunate in six states.
The project involved raising awareness
about the benefits of injectable arte-
sunate, securing funding for procure-
ment, training of health-care workers,
quantifying the need and monitoring the
impact of the switch from quinine.
Artesun® (injectable artesunate)
WHO prequalified
Indication: Severe malaria
Advantages:
to previous standard of care (quinine)
in Africa1 2
Project Leader:
ceutical
Partner:
MMV Project Director:
Severe malaria: saving lives, changing practice
1 Dondorp AM et al. “Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.” Lancet. 376(9753):1647-57 (2010).
2 Dondorp A et al. “Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.” Lancet. 366(9487):717-25 (2005).
Saudat is 3 years old. On 27 August 2012, she was
admitted to Murtala Mohammed Specialist Hospi-
tal in Kano State in northern Nigeria. She was un-
conscious and convulsing with a temperature of
38.9 °C. She had severe malaria. Her life was at risk.
Injectable artesunate (Artesun® 60 mg) was administered
immediately, and then regularly for a period of 48 hours.
Two days later, Saudat gained consciousness and was put
on a regimen of Coartem® (artemether-lumefantrine), an
oral artemisinin-based combination therapy (ACT), to com-
plete her cure. Injectable artesunate had helped reduce the
severity of her malaria infection and saved her life.
“Working in malaria, and especially in access and delivery
of antimalarials, is challenging,” said Pierre Hugo, Project
Director for the MMV Access team. “Seeing Saudat recov-
er so quickly was amazing. It’s hugely satisfying to see a
product that we have supported put to use, and truly
humbling to meet the health-care providers who save lives
on a daily basis.”
Saving Saudat
21
3 World Health Organization. World Malaria Report 2012: www.who.int/malaria/publications/world_malaria_report_2012/en/
4 Guilin Pharmaceutical (Shanghai) Co., Ltd.
(GPSC) is working to overcome this issue and has submitted 30 mg and 120 mg packs of injectable artesunate for WHO prequalification.
Dr Binta Jibir Wudil
Head of Paediatrics at Murtala
Mohammed Specialist Hospital
(MMSH), Kano State, Nigeria, ex-
plains the benefits of injectable
artesunate and how Kano State is
addressing the challenges of im-
plementation.
The burden of severe malaria in
Nigeria is one of the highest in
the world.3 What progress has
been made at MMSH to improve
its treatment?
We recently learnt of the benefits of
using injectable artesunate in place
of quinine for the treatment of severe
malaria and decided to try it. We were
really impressed; its performance was
excellent.
In August last year, 30% of our out-
patient cases had severe malaria. We
used injectable artesunate for all the
cases and found it to be very effective
and easy to administer. Given the large
number of patients and the fact that we
were also short staffed, it made a big
difference that the treatment was much
less onerous. A little girl, Saudat made a
complete recovery. This helped us de-
cide to switch from quinine to injectable
artesunate for all admitted cases of se-
vere malaria. The Kano State Hospital
Management Board is now also procur-
ing the medicine for other hospitals in
the state.
What advantages have you found
in using injectable artesunate vs
quinine to treat severe malaria?
First of all, children who might be coma-
tose due to the effects of malaria recover
much quicker. Before, if we had a child
who was anaemic with severe mala-
ria, we would need to perform a blood
transfusion to treat the anaemia first,
as quinine can exacerbate symptoms
of malaria, like anaemia, haemolysis,
haemoglobinuria (black water fever) and
hypoglycaemia. The issue with quinine
is that there is a very narrow treatment
window. You really have to get the dose
right – too little and the parasite will
take over, too much can lead to com-
plications. In the worst case, if quinine is
administered too quickly, it can have an
effect on the heart and patients can die.
Artesunate is much easier to use. The
injection is intravenous or intramuscular
and it takes 1–2 minutes to administer,
whereas quinine takes 4 hours. Also,
the treatment window is larger with
injectable artesunate, so we have fewer
complications.
In addition, we have found that injectable
artesunate is more cost-effective overall.
Although the cost of the vials is higher,
when you take into account the costs
of intravenous fluids needed for quinine,
the time of the health-care workers
and the duration of the patient’s stay,
injectable artesunate is actually cheaper.
What challenges did you face
in switching from quinine to
injectable artesunate?
The first challenge was training people
how to use a new treatment. Injectable
artesunate needs to be reconstituted by
adding sodium bicarbonate and then
diluting with saline. The other potential
challenge is wastage, especially in low-
body-weight children. Once a vial has
been opened, it must be used immedi-
ately or discarded. It cannot be reused.
Ideally, we need a paediatric formulation
smaller than the current 60 mg packs.4
What’s the benefit of working with
MMV and partners in making the
switch?
MMV and CHAI organized the training
for health-care workers to use injectable
artesunate correctly. They provided us
with posters that clearly show how injec-
table artesunate can be used. That was
very helpful.
Based on the knowledge ac-
quired in the DRC and Nigeria,
MMV has created a severe ma-
laria consortium together with CHAI
and Malaria Consortium. This MMV-led
team has been awarded a grant of ap-
proximately USD 34 million by the
UNITAID board to fund procurement and
scale-up of injectable artesunate across
13 states in Nigeria and in five other
countries with a high malaria burden
(Cameroon, Ethiopia, Kenya, Malawi
and Uganda).
The UNITAID funding will also help ac-
celerate the development of a WHO-
prequalified intrarectal artesunate for
pre-referral management of patients
with severe malaria. MMV hopes to
build upon clinical studies conducted
by WHO’s special tropical diseases
programme (TDR), to bring the drug
through the approval process and then
to patients.
Based on case estimates, up to 50 mil-
lion vials of injectable artesunate may be
needed each year. Current production
covers only 10% of patients leaving 90%
without access to the drug. The UNITAID
project seeks to reduce this gap, while
stimulating greater market competition
and eventually lowering prices for this
important drug.
To guide the optimal use of injectable
artesunate, MMV is also taking the lead
in assessing the real-life safety of the
medicine,* as the scale-up proceeds.
Since WHO prequalification in 2010,
close to 6 million vials of Guilin’s injec-
table artesunate have been delivered.
Based on average dosage requirements
and survival rates from the AQUAMAT1
and SEAQUAMAT2 trials, this scale-up is
estimated to have saved 40,000–50,000
additional lives compared to treatment
with quinine.
* Late onset haemolysis has been reported with the use of injectable artesunate. Published reports recommend that treatment with injectable artesunate should be limited to the required period and followed by a full course of an oral antimalarial, in line with WHO recommendations. Monitoring for late haemolytic anaemia should occur in all cases of severe malaria, irrespective of treatment.
4 | Medicines for vulnerable populations
22
“
replacement for
prevention is an
important priority.”
Thirty two million pregnant wo-
men run the risk of contracting
malaria each year in sub-Saha-
ran Africa.2 They are far more likely to
become ill and to die from the disease
than non-pregnant women as their im-
mune response is lower.3 Two lives are
at stake, not just one: malaria during
pregnancy doubles the risk of delivering
a child with low birth weight, and is also
responsible for up to 200,000 infant
deaths each year.4
To protect pregnant women living in
areas of moderate-to-high malaria trans-
mission, WHO recommends use of the
antimalarial sulfadoxine-pyrimethamine
(SP), administered ideally at three ante-
natal care visits, at least 1 month apart.5
This approach is known as IPTp.6
However, parasite resistance to SP is
emerging and reported in up to 88%
of malaria-infected pregnant women in
some populations.7
New treatment regimens are urgently
needed today. With this in mind, and
owing to the scientific and ethical com-
plexity of developing medicines for preg-
nant women, MMV and Pfizer are jointly
creating a new regimen from compounds
that have already been demonstrated to
be well-tolerated in pregnant women.
Azithromycin-chloroquine (AZ-CQ), is a
combination of an antimalarial (CQ) and
an antibiotic (AZ) that will also treat some
sexually transmitted infections and thus
improve overall birth outcomes. The plan
is to submit the dossier for regulatory
approval in 2014.
1 Chico RM et al. “Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy.” Malar J. 7:255 (2008).
2 World Health Organization. World Malaria Report 2012. www.who.int/malaria/publications/world_malaria_report_2012/wmr2012_full_report.pdf
3 Duffy PE, Fried M. “Malaria in the pregnant woman.” Curr Top Microbiol Immunol. 295:169-200 (2005).
4 Conroy AL et al. “Complement activation and the resulting placental vascular insufficiency drives fetal growth restriction associated with placental malaria.” Cell Host Microbe. 13(2):215-26 (2013).
5 World Health Organization. Updated WHO Policy Recommendation (October 2012). Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP). www.who.int/malaria/iptp_sp_updated_policy_recommendation_en_102012.pdf
6 Intermittent Preventive Treatment in pregnancy (IPTp) is the administration of a full course of an effective antimalarial treatment to pregnant women living at risk of malaria. It should only be administered after their first trimester and at a minimum of 1-month intervals.
7 Iriemenam NC et al. “Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya.” Malar J. 11:134 (2012)
8 Seasonal Malaria Chemoprevention: previously termed intermittent preventive treatment in children, is the intermittent administration of full treatment courses of an effective antimalarial medicine during the malaria season to prevent malarial illness.
9 As noted in WHO Policy Recommendation, March 2012: “SMC with AQ plus SP is not currently recommended for countries in southern and eastern Africa, even though there are some locations where the
transmission pattern would suggest suitability, because of the high level of P. falciparum resistance to AQ and/or SP, and the absence of adequate efficacy and safety data for other potential antimalarial regimens for use in SMC.” www.who.int/malaria/publications/atoz/smc_policy_recommendation_en_032012.pdf
10 World Health Organization. WHO policy recommendation: Seasonal malaria chemoprevention (SMC) for Plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-region in Africa. (2012). www.who.int/malaria/publications/atoz/who_smc_policy_recommendation/en/index.html
11 Cairns M et al. “Estimating the potential public health impact of seasonal malaria chemoprevention in African children.” Nat Commun. 3:881. (2012).
chloroquine (AZ-CQ)
Phase III
Target indication:
Advantages:
diseases leading to improved birth
outcomes
overcoming any potential parasite
resistance to chloroquine1
Project Leader: Dr Richa Chandra,
Partners:
School of Hygiene & Tropical Medicine, UK
MMV Project Director: Dr Wiweka
Protecting vulnerable patients
23
Prof. Brian Greenwood
Department of Clinical Tropical
Medicine at the London School of
Hygiene & Tropical Medicine, UK,
has worked for decades in Africa
researching and treating malaria.
He explains the role of preventive
therapy and approaches to its
scale-up and widespread use.
What place do preventive treat-
ments have versus diagnosis and
treatment in the control of malaria
in vulnerable groups?
There is always a balance between the
two approaches and the decision which
to use has to be determined by the inci-
dence of malaria. Where the risk of clini-
cal attacks is high, it makes sense to give
drugs for prevention to everyone. But as
the incidence goes down, that approach
is no longer cost effective, as only a small
proportion of people will benefit from the
drugs, and all drugs pose some risk.
What is the role of
preventive treatments versus
a potential vaccine?
Should a vaccine come along that is
more than 80% effective then it would
be deployed instead of preventive treat-
ments. However, I think it could be at
least 10 years before this happens.
There is a risk to developing a new pre-
ventive treatment ready for use in 3–4
years’ time, as it might only have a life-
span of 5 years, but given the many lives
that could be saved even in that time
frame, it is a risk worth taking.
What are the priority research
areas for preventive treatments?
The entire field of research into pre-
ventive treatments is relatively new as,
rightly so, the main focus has been on
treatment. Developing an SP replace-
ment for prevention is an important
priority. SP was the medicine first used
for IPTp and then later in infants and
more recently as Seasonal Malaria
Children account for the vast
majority of malaria deaths
and in some parts of Africa
mortality rates are particularly high
during and immediately after the
rainy season. Around 39 million
children under the age of 5 years live
in areas of seasonal malaria where
an estimated 152,000 die each
year.11
Young children can be protected at
times of risk with monthly courses
of an antimalarial drug combina-
tion SMC which could avert several
million new cases and save tens of
thousands of lives.10
To implement WHO’s recommen-
dation, MMV is working with Guilin
Pharmaceutical to obtain WHO pre-
qualification for SP+AQ. In particu-
lar, MMV is working to make drug
dispensing easier by supporting
the development of a lower-dose
formulation for younger children,
blister packaging and, eventually,
a dispersible formulation.
Chemoprovention (SMC)8 in combina-
tion with amodiaquine (AQ) for older
children. It was chosen owing to its
long-acting nature, which is important
for prevention. It works in the Sahel and
sub-Sahelian countries, where WHO
just recommended SP+AQ for SMC,
but there is growing resistance to SP in
southern and eastern Africa. So its use
there would be inappropriate.
How can the use of effective
preventive therapies, like SP+AQ,
be expanded?
As with all interventions, there are a num-
ber of bridges to be crossed between a
WHO recommendation and implemen-
tation. The push to deploy SMC needs
to come from endemic countries – but
they will need some help.
Malaria control is becoming a lot more
complicated and implementing a new
tool is hard work, putting a strain on
National Malaria Control Programmes,
some of which have very limited re-
sources. WHO has been in discussions
with ministries of health in endemic
countries, such as Senegal, to see how
it can help, for example by developing
implementation guidelines. Médecins
Sans Frontières has done some work
in Mali and Chad. Now that SMC is
recommended by WHO, countries can
include it in their funding requests to
international donors such as the Global
Fund.
Implementing a new intervention suc-
cessfully needs local champions. African
scientists have been involved from the
outset in the trials of SP+AQ and so the
ownership is there.
MMV has been very helpful in initiating
dialogue on how to make the drugs
used for SMC as cheap as possible and
easy to administer, as well as looking at
developing other long-acting drugs.
Sulfadoxine- pyrimethamine + amodiaquine
Working towards WHO prequalification
Target indication: Seasonal Malaria
Chemoprevention (SMC) in children in
areas of highly seasonal transmission
across the Sahel sub-region of Africa9
Advantages:
10
Project Leader:
ceutical
Partners:
of Hygiene & Tropical Medicine, UK
MMV Project Director: Aleksandra
Misiorowska
24
5 Medicines for malaria
elimination/eradication
To achieve malaria elimination/
eradication, it is necessary to
achieve radical cure at the in-
dividual level and eliminate the human
transmission reservoir at the popula-
tion level. Medicines are considered
most likely to achieve eradication if ad-
min istered with effective transmission
prevention tools.
MMV is uniquely positioned to contrib-
ute to the elimination and eventual erad-
ication of malaria by:
Re-purposing existing malaria
medicines for use in short-term
elimination efforts.
Developing a well-tolerated,
first-generation SERCaP (single
encounter radical cure and prophy-
laxis) with a combination of drugs
that meet stringent target candi-
date profiles (TCPs) (page 17) for
large-scale administration to both
symptomatic and asymptomatic
infected populations including
children and pregnant women.
Developing the components of a
second-generation SERCaP to
address the inevitable emergence
of drug resistance.
blocking activity. For example,
the investigational ‘single-dose’
cures OZ439 and KAE609 have both
demonstrated transmission-blocking
potential in the laboratory, in addition to
their established blood-stage activity.2,3
The key now is to investigate this poten-
tial further by tracking the development
of the parasite between patients and
mosquitoes, after treatment with either
OZ439 or KAE609. We are also working
with scientists in Tanzania to establish
an insectary and proof-of-concept
(Phase IIa) transmission-blocking mo-
del, which can then be used to test
and confirm these and other laboratory
findings.
In parallel, the hunt continues for novel
compounds able to cure and block the
transmission of malaria in the long-term.
We are working with partners to deve-
lop assays4 capable of screening a high
number of compounds at one time. The
goal over the coming year is to screen
many of the 25,000 blood-stage active
molecules that emerged from the exten-
sive malaria screening campaign of more
than six million compounds.5
To eliminate the reservoir of para-
sites that continues transmis-
sion to the next person we need
medicines that target the sexual-stage
parasites (which are taken up by the
mosquito and continue the parasite’s
lifecycle). To do so, MMV has a three-
pronged strategy addressing short-,
medium- and long-term needs.
In the short-term, in line with WHO’s
recent recommendation for a single low
dose of primaquine to be taken along-
side ACTs to block transmission,1 MMV
will work in partnership to develop and
obtain WHO prequalification for addi-
tional peadiatric ACTs. Additionally, as
primaquine has been in use for more
than 60 years and with its use set to
increase, there is a risk its efficacy might
start to decline. As a result, MMV is
also researching alternatives for the
medium-term, such as tafenoquine in
partnership with GSK.
To further address medium-term
needs, our approach is to look at the
candidate molecules we already have
in preclinical development, to see how
they match primaquine’s transmission-
1 World Health Organization. Updated WHO Policy Recommendation (October 2012): www.who.int/malaria/diagnosis_treatment/treatment/who_pq_policy_recommendation/en/
2 Delves M et al. “The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites.” PLoS Med. 9(2):e1001169 (2012).
3 van Pelt-Koops JC et al. “The spiroindolone drug candidate KAE609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.” Antimicrob Agents Chemother. 56(7):3544-8 (2012).
4 Assay: a laboratory-based platform with which to conduct experiments such as whether a molecule is able to kill the malaria parasite.
5 Collaborations with pharmaceutical companies (including GSK, Sanofi, Novartis, Pfizer, Genzyme and AstraZeneca) as well as academic institutions such as St Jude Children’s Research Hospital, led to the screening of more than six million compounds resulting in 25,000 chemical starting points with activity against P. falciparum.
Blocking transmission
Fluorescent-stained
late-stage gametocyte,
courtesy of V. Avery
Griffith University,
Australia
25
Prof. Robert Sauerwein
Head of the Division of Medical
Parasitology and Centre for Clini-
cal Malaria Studies, Nijmegen In-
stitute, the Netherlands, is adapting
assays4 to identify transmission-
blocking molecules. He talks about
the assays and what it’s like to
work with MMV.
How do these assays work?
We incubate gametocytes with the test
compounds in microtiter plates and
assess at what concentration they kill
the gametocytes, if at all. We use a
Plasmodium lactate dehydrogenase
(pLDH) test that can tell us whether the
parasites are alive or not at different
stages of their development.
We also use a standard membrane-
feeding assay, which enables us to
investigate what is happening in the
mosquito. This is a well-established
assay and the closest to reality. We allow
mosquitoes to feed on infected blood in
the presence or absence of drug and
study whether the parasite continues to
develop within the mosquito.
We have validated and standardized the
assay with test compounds with known
activity and are now looking to improve
the read-out system. At the moment we
use microscopy, which is very labour-
intensive. The next step is to move
from a 96-well plate to a 384-well plate,
which will significantly increase the nu-
mber of molecules we can screen at
once. We hope to be able to screen a
few thousand compounds in a year.
What is the added value of work-
ing with MMV on this project?
MMV is in a special position as it works
across the board, from discovery to
characterizing molecules and clinically
developing them.
The organization really bridges academic
activities and drug development – there
are not many that do that. It’s the global
coordination of these activities that
really makes MMV special. As an aca-
demic with an interest in transla tional
medicine, for me they are an ideal
partner. MMV helps us translate our
find ings through to clinical development.
Our objectives are aligned.
We work well together and have regular
reporting back and forth. It’s not like an
academic project where you send your
report to an administrator once a year
who checks to see if your report looks
nice. No, MMV really has knowledge
of the project and co-orchestrates its
progress, so it really is a partnership.
Dr Salim Abdulla
Chief Executive Director, Ifakara
Health Institute, Tanzania, is
working with MMV to establish
an insectary and clinical research
centre in Bagamoyo. He explains
how the work ahead determines
the transmission blocking activity
of in-development medicines.
How will the research facility be
used?
The site will be used to see if different
drugs can prevent the transfer of par-
asites from humans to mosquitoes.
There are several ways to do this. Some
are already established and others will
need to be developed.
The established way is to culture par-
asites until gametocytes are formed.
We then take blood from people who
have been treated with different drugs
and combine it with the gametocytes
to see whether the residual drug in the
blood can kill the gametocytes. This is
experimental and fast, but most people
would argue that they want to see the
real thing.
The most realistic approach is to look
at patients with malaria that have
been treated with potential transmis-
sion-blocking drugs, to see how many
gametocytes develop and how infec-
tious they are. We do this by watching
patients for 7–14 days to see what
happens when mosquitoes feed on
their blood – either directly or through
membrane feeding. We want to know
whether or not the gametocytes remain
viable and develop in the mosquito. If
the medicine administered can block
transmission, we will see fewer or no
mosquitoes carrying parasites.
Which molecules will you study?
The most promising transmis-
sion-blocking molecules are the synthe-
tic peroxides, so we will look at MMV’s
OZ439 first and then other new com-
pounds coming through with different
methods of action, such as KAE609.
We will also look at different compounds
on the market, such as primaquine
artemether-lumefantrine and di hydro-
artemisinin-piperaquine, to help establish
a benchmark for comparison.
How has working with MMV
helped to strengthen the research
capacity of the Bagamoyo site?
We have been working with MMV since
2005, and the relationship has really in-
creased the knowledge and skill base of
the scientists at Bagamoyo. MMV has also
contributed to the infrastructure, such as
the laboratory and clinical platforms. This
is a huge boost to the research capacity
here and the site can now also be used for
vaccine development.
For me personally, the process of talk-
ing to people with a great deal of ex-
perience has allowed me to better un-
derstand how to be successful in this
field. Overall, the work with MMV is
very interesting. It has also allowed us to
explore new ways of doing things and
to look beyond already established mo-
dels. This is where it really starts to get
interesting.
5 | Medicines for malaria elimination/eradication
26
Tafenoquine
Phase IIb
Target indication: Liver stage of P. vivax
(relapsing malaria)
Advantages:
therefore better compliance
Project Leader:
GlaxoSmithKline
Partner: GlaxoSmithKline plc., UK
MMV Project Director: Dr Wiweka
While the parasite, Plasmo-
dium falciparum, is res-
ponsible for the majority of
the annual 610,000–971,000 global
malaria deaths,1 Plasmodium vivax re-
sults in 70–80 million cases each year.2
In addition, severe complications are
increasingly being associated with
P. vivax malaria; the long-held per-
ception that this is a benign form of
malaria is changing.3
The high burden of disease is partly due
to P. vivax’s ability to lie dormant in the
liver and reactivate at any time, leading
to intense malaria symptoms in the ab-
sence of a new mosquito bite. Known
as ‘relapsing malaria’, the disease is
prevalent in south-east Asia, India and
South America and parts of Africa,
where millions of work and schooldays
are lost every year as a result.2,3 Studies
also show that it has adverse effects on
children’s cognitive ability.4,5 This tiny
par asite traps families and communities
in an endless cycle of poverty, hindering
social and economic development.
The only approved anti-relapse medicine
able to eliminate the dormant liver-stage
form (the hypnozoite) is primaquine,
which has a 14-day treatment regimen,
making compliance difficult to achieve.
It is also associated with potentially
fatal haemolytic side effects in patients
deficient in the enzyme glucose-6-
phosphate dehydrogenase (G6PD).6,7
Additionally, it has been in use for
approximately 60 years and so the risk
of resistance is ever present. Our goal
to eradicate malaria cannot be achieved
without new anti-relapse medicines.
Tafenoquine, currently in clinical develop-
ment with MMV and GlaxoSmithKline
(GSK), is the lead candidate to provide
an alternative option to primaquine. Stu-
dies show it could be taken as a single
dose – a significant improvement on
primaquine’s 14-day course. However,
tafenoquine is from the same chemical
family as primaquine and also likely to be
associated with the same side effects in
G6PD-deficient patients.
To have a better understanding of the
prevalence of G6PD deficiency and
the use of primaquine, MMV and GSK
conducted market research in India,
Indonesia and Brazil. The research re-
vealed widespread use of primaquine
without G6PD testing and limited aware-
ness of risk, suggesting the need for a
convenient and affordable G6PD de-
ficiency test. MMV plans to work with
GSK and PATH to explore the develop-
ment of a test suitable for field use.
1 World Health Organization. World Malaria Report 2012: www.who.int/malaria/publications/world_malaria_report_2012/en/
2 Mendis K at al. “The neglected burden of Plasmodium vivax malaria.” Am J Trop Med Hyg. 64(1-2 Suppl):97-106 (2001).
3 Price RN et al. “Vivax malaria: neglected and not benign.” Am J Trop Med Hyg 77:79–87 (2007).
4 Vitor-Silva S et al. “Malaria is associated with poor school performance in an endemic area of the Brazilian Amazon.” Malar J. 8:230 (2009).
5 Fernando SD et al. “The ‘hidden’ burden of malaria: cognitive impairment following infection.” Malar J. 9:366 (2010).
6 Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme involved in protecting all human cells from oxidative stress. Deficiency in this enzyme is thought to have co-evolved with malaria as it offers a degree of protection against severe malaria.
7 Wells TN, Burrows JN, Baird JK. “Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to malaria elimination.” Trends Parasitol. 2010 26(3):145-51 (2010).
Stopping the relapse
To be able to test the efficacy of new
anti-relapse medicines in the real world,
we need to know whether a repeat
infection is due to relapse or to a new
infection from a new mosquito bite. This
can be a challenge in malaria-endemic
countries. To overcome this, MMV is col-
laborating with Colonel Bagus Tjahjono,
Indonesian Army Health Command and
Dr Kevin Baird, Eijkman Oxford Clinical
Research Unit, on the development and
validation of an innovative clinical model.
The model looks at soldiers in Indone-
sia who are at risk of contracting malaria
during their tour of duty in north-eastern
Papua. When they return to base in East
Java, where there is no malaria trans-
mission, they are tested for the disease.
If positive, they are treated with an ACT.
If the symptoms of malaria reappear af-
ter treatment, we can be sure they are
due to a relapse and not a new infection.
So far, the model has been used to ex-
plore the efficacy of primaquine given
28 days after a treatment of the blood-
stage parasites with the ACT dihydro-
artemisinin-piperaquine. The next step is
to investigate the efficacy of primaquine
given together with dihydroartemisinin-
piperaquine and other ACTs, and then
next-generation anti-relapse medicines
like tafenoquine.
Malaria relapse or completely new infection?
Fluorescent-stained P. vivax
persistent liver forms (in pink),
courtesy of S. March-Riera
& S. Bhatia, Massachusetts
Institute of Technology, USA
27
What progress has been made
so far?
We’ve found that some of our com-
pounds already in development have
activity against the hypnozoite as well as
the blood stages. One promising chemi-
cal series has recently transitioned from
discovery to preclinical development,
and several others show some signs of
activity.
As for the assays, the cell assay based
on rodent parasites has been improved
and is now ready to be used for the
screening of a large library of 500,000
compounds. This will help us pre-
screen to see which compounds real-
ly can work in liver tissue. We will then
progress interesting liver-stage hits into
a specific hypnozoite assay.
The P. vivax cell assays are also pro-
gressing well. With the support of the
Gates Foundation, Prof. Sangeeta
Bhatia of Massachusetts Institute of
Technology has developed a new culture
system that may provide the assay we
need to identify the next-generation
anti-relapse medicine.11 We hope to be
able to demonstrate feasibility of such
an assay and begin high-throughput
screening in the coming years.
8 Cell or in vitro assay: using components of an organism isolated from their usual biological surroundings to test, in this case, the efficacy of molecules to kill the dormant liver stage of P. vivax malaria; also known as a ‘test tube model’.
9 Biological in vivo assay: using a living organism, in this case to test the efficacy of a molecule to kill the dormant liver stage of malaria; also known as an ‘animal model’.
10 Between 2008–2012, MMV and partners screened more than six million molecules for activity against the blood stage of malaria, leading to the identification of 25,000 chemical compounds. Given the priority and unmet medical need for P. vivax malaria, we would plan a similar screening campaign against this parasite.
11 Khetani SR, Bhatia SN. “Microscale culture of human liver cells for drug development.” Nat Biotechnol. (1):120-6 (2008).
Dr Brice Campo
Associate Director of Drug Disco-
very, MMV, explains the research
challenges presented by P. vivax
and MMV’s discovery strategy to
stop the relapse.
Why have so few medicines been
discovered and developed to
treat relapsing malaria?
For a long time, the species P. vivax was
considered benign and so focus was
placed on the more lethal P. falciparum.
We now know P. vivax is far from benign
and so it is starting to get the attention
it deserves.
Up until 5 years ago, there were a lack
of suitable assays in which to test po-
tential molecules: there was no cell
assay8 and the only biological assay9
relied on a substitute primate model of
infection. Significant progress has been
made; we now also have a substitute
rodent cell assay that can be used to
prioritize testing. However, we are not
yet using human parasites, so some
molecules active solely against P. vivax
could be missed.
What is MMV’s discovery strategy
to identify anti-relapse
molecules?
To be pragmatic and until we have a
P. vivax cell assay, we plan to use cur-
rently available cell assays to screen
each of the blood-stage active series in
our portfolio.
In parallel, MMV and the Bill & Melin-
da Gates Foundation are working with
different groups to develop the optimal
assay: a cost-effective P. vivax cell as-
say able to screen large numbers of
compounds at the same time. One of
the biggest challenges is gaining access
to sporozoites (which are used to infect
liver cells and generate hypnozoites).
We are working with partners in disease-
endemic countries such as India, Peru
and Thailand, which have laboratory
facilities to dissect sporozoites from
mosquitoes that have fed on infected
blood. In addition, we have partners
in the USA who are working to culture
P. vivax parasites in the lab, which
simplifies the sporozoite supply issue.
Because this is such a challenging area
of research it’s important to integrate our
activities and share knowledge between
the groups. MMV is taking a key role in
this integration process.
All being well, in the next 5 years we plan
to screen as many compounds as pos-
sible for activity against the hypnozoite
of P. vivax.10 It’s an ambitious goal, as
no one has been able to do this in a
low- let alone a high-throughput fashion
before. If we are successful with these
approaches we will have made a huge
advance towards identifying the next-
generation of anti-relapse medicines.
5 | Medicines for malaria elimination/eradication
28
In 2011, MMV launched the Open
Source Drug Discovery (OSDD)
programme working with scientists
initially in Australia and then in India.
With many compounds to investigate,
following the identification of more than
25,000 active molecules, we need as
many of the world’s best scientific minds
as possible working together.
OSDD differs from traditional drug
discovery, which is commercially driven
and typically conducted behind closed
doors with limited information released
into the public domain until patents
are published. Given the minimal
commercial value of new medicines
against malaria and neglected diseases,
we have an opportunity to explore how
this paradigm can be changed.
Since 2011, MMV has been collabora-
ting with Dr Mat Todd at the University
of Sydney, Australia, to discover new
molecules active against malaria. Mat
posts all the details of his research onto
a website, The Synaptic Leap,1 using a
kind of ‘electronic lab book’. As posts
are added, alerts go out via social me-
dia. Scientists from around the world
can then input their expertise and
contribute to the project’s progress.
Some laboratories have even contri-
buted by synthesizing and screening
compounds. With many people work-
ing in parallel, problems can be solved
quickly. This initiative is the first to show
the approach can work for drug disco-
very and has thus paved the way for
other open source projects.
MMV is now also working closely with
India’s OSDD malaria programme2 to in-
vestigate the most promising compound
series, initially for blood-stage malaria.
However, given the burden of relapsing
malaria in India, the ultimate objective is
to identify molecules capable of target-
ing the liver stage to stop the relapse.
The MMV/OSDD partnership also has
the scope and potential to progress
mole cules through preclinical and clinical
development.
1 The Synaptic Leap: www.thesynapticleap.org2 Open Source Drug Discovery India: www.osdd.net/home3 National Center for Biotechnology Information
PubChem: pubchem.ncbi.nlm.nih.gov4 ChEMBL database: www.ebi.ac.uk/chembl/malaria/
OSDD powering the pipeline and changing the paradigm
Dr Tanjore Balganesh
Project Head at India’s OSDD Ini-
tiative, explains how open source
research is taking off in India.
What are the objectives of India’s
OSDD model?
The ultimate objective is to provide afford-
able health care to patients. To that end,
OSDD consolidates research for new
therapies for neglected diseases (mala-
ria, tuberculosis and leishmaniasis). The
idea is that the products developed will be
licenced to India’s Council of Scientific &
Industrial Research (CSIR), and then to the
generics industry without royalties, which
will help keep the cost of the medicine low
and increase patient access.
How can scientists participate in
OSDD?
We employ a crowdsourcing model:
CSIR-funded scientists working to discov-
er promising molecules, share their re-
sults and problems via an online platform.
Researchers from around the world, from
product development partnerships, small
and large pharma – basically anyone with
an interest in the research – offer their ad-
vice via the platform.
What are the advantages of the
model?
The major advantage is increased scien-
tific capability as it brings more minds
together. Also, because the model uses
public funds the final products will be af-
fordable. We hope that the platform will
encourage the formation of new research
collaborations.
How do you encourage scientists
to join the platform?
We offer scientists the opportunity to
screen their molecules free of charge.
We have built speciality centres where
they can get specific information on their
compounds. We hope to do the same
for malaria in the next 6 months. We
also offer opportunities to collaborate
with other scientists: consultants and
experts who can help expedite their
work. We simply request that if they use
the facilities they share their data.
What will success look like?
The first success we are hoping for in
2013 is to set up facilities in India where
scientists can conduct clinical research
studies for TB, malaria and neglected
diseases. Today, in India, there are
limited public or private institutions
where you can do so. I strongly believe
that once these platforms have been set
up it will encourage further research and
incentivize biotech and pharma compa-
nies to re-evaluate molecules previously
deemed low-priority, as it will cost little.
This will be the first step to establishing
drug research excellence in India.
What’s the advantage of working
with MMV?
MMV offers us access to high-quality
expertise via its global networks. MMV
has the best experience in progressing
molecules in malaria. OSDD would like
to tap into that experience and learn
from it. I think our success is very much
dependent on MMV’s contribution. If
you take MMV off the OSDD radar it’s a
recipe for failure.
I’ve worked with MMV for many years,
and the key thing it offers is the culture
of collaboration. The people are real-
ly great to work with. I have worked
with Tim Wells and Jeremy Burrows
on MMV’s science team and know I
can pick up the phone and say, “Jere-
my, I have a problem” and he will help.
Otherwise, it just wouldn’t work.
29
van Pelt-Koops JC et al. “The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.” Antimicrob Agents Chemother. 56(7):3544-8 (2012).
Details transmission-blocking potential of the first novel-acting antimalarial compound to enter Phase II in 20 years.
Sanz LM et al. “P. falciparum in vitro killing rates allow to discriminate between diffe-rent antimalarial mode-of-action.” PLoS One. 7(2):e30949 (2012).
High-priority paper as it represents a paradigm shift in assessing the killing rate of antimalarial compounds.
Delves M et al. “The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites.”PLoS Med. 9(2):e1001169 (2012).
Details the activity of marketed and in-development medicines at each stage in the parasite’s lifecycle, providing invaluable insight into which drugs to combine for next-generation antimalarials.
Younis Y et al. “3,5-Diaryl-2-aminopyridines as a novel class of orally active anti-malarials demonstrating single dose cure in mice and clinical candidate potential.”J Med Chem. 55(7):3479-87 (2012).
Demonstrates the potent antimalarial potential of the aminopyridine compound, MMV390048 – selected as MMV’s Project of the Year 2012.
Kayentao K et al. “Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial.” Malar J. 11:364 (2012).
Pivotal Phase II study demonstrating pyronaridine-artesunate paediatric formulation is efficacious and non-inferior to the current gold standard paediatric formulation.
Ding XC et al. “A framework for assessing the risk of resistance for anti-malarials in development.” Malar J. 11:292 (2012).
Details a methodology to assess the susceptibility of new antimalarial compounds to the develop-ment of drug resistance – a critical tool in prioriti-zation of new compounds.
Anthony MP et al. “The global pipeline of new medicines for the control and elimi-nation of malaria.” Malar J. 11:316 (2012).
Key paper summarizing the current status of the global pipeline of antimalarial medicines and the challenges ahead if malaria elimination is to be achieved.
Talisuna AO et al. “Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study.” Malar J. 11:356 (2012).
Pilot study demonstrating that subsidizing the cost of quality ACTs along with targeted communications can significantly increase their uptake and use in the private sector.
Top 10 MMV publications of 2012
Some 20,000 structures active against
malaria have been released into the
public domain3 as a result of the
screening efforts at St Jude Children’s
Research Hospital, Tennessee (USA),
Novartis and GlaxoSmithKline. Yet,
researchers need physical access to
the compounds to be able to work
with them. In response to this need,
MMV set up the Malaria Box project.
The Malaria Box is a treasure trove of
400 diverse compounds selected from
these original active hits. Compounds
were clustered into chemical families,
and members chosen based on their
structures and availability.
In 2012, MMV and the Bill & Melinda
Gates Foundation each offered 12
grants for scientists working on Malaria
Box compounds, with projects seeking
to establish mechanisms of action, re-
sistance profiles as well as activity on
other related parasites.
To continue the virtuous cycle of re-
search, Malaria Box recipients are re-
quested to place all data generated on
the compounds into the public domain
via the ChEMBL database.4 Hosted by
the European Molecular Biology Labo-
ratory-European Bioinformatics Institute
(EMBL-EBI), the database provides a
one-stop shop for all publicly available
malaria drug research in one easy-to-
search format.
By the end of 2012, 103 copies of
MMV’s Open Access Malaria Box had
been dispatched to 26 countries to ca-
talyze malaria and neglected diseases’
drug research.
To date, the Drugs for Neglected
Diseases initiative (DNDi), has identi-
fied several chemical series with activity
against sleeping sickness and leishman-
iasis from the Malaria Box compounds.
The results have since been shared with
the community via ChEMBL.
Malaria Box
Rueangweerayut R et al. “Pyronaridine-artesunate versus mefloquine plus artesunate for malaria.” N Engl J Med. 366(14):1298-309 (2012).
Pivotal Phase III study demonstrating the safety and efficacy of pyronaridine-artesunate.
Moehrle J et al. “First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide anti-malarials.” Br J Clin Pharmacol. 75(2):524-37 (2013).
Demonstrates the safety and pharmacokinetic profile of OZ439, enabling progression of the compound to malaria patients.
5 | Medicines for malaria elimination/eradication
30
MMV Project of the Year 2012
Prof. Kelly Chibale
Founder and Director of the Univer-
sity of Cape Town’s Drug Discovery
and Development Centre (H3-D),
was the Project Leader of the UCT
team that delivered MMV390048 as
a preclinical candidate.
What is special about the
collaboration that identified the
compound?
The project was not conducted using
the traditional pharmaceutical industry
model but the product development
partnership model of MMV. We
worked with partners from across the
world: Griffith University and Monash
University, both in Australia, Swiss
TPH, and Syngene in India. That’s what
makes it special. Academic institutions
worked together under the mentorship
of experienced scientists from pharma,
specifically Mike Witty of MMV’s Expert
Scientific Advisory Committee (ESAC)
and David Waterson (MMV Project
Director), with some key assays carried
out by GlaxoSmithKline (GSK). Without
MMV’s network the project would simply
not have got this far.
How did you coordinate the input
of different partners from all over
the world?
From the outset, MMV set clear pro-
gression criteria and a need to inte-
grate all activities. This meant regular
meetings. We held biweekly chemistry
meetings and monthly project meetings,
with all partners. But nothing beats
face-to-face, so we also had two meet-
ings each year where everyone came
together under one roof to discuss all
the data and the next steps. The project
management provided by MMV was a
critical ingredient.
Are there any other advantages
of working with MMV on this kind
of project?
MMV gave us a head start by provid-
ing access to a good project and the
starting points selected from a library
of drug-like molecules. As Tim Wells
(MMV’s Chief Scientific Officer) once
said, by working from such a library
“we start in year 4 instead of year 1”.
Also, by working with MMV, we knew
that our project was globally aligned,
and the work would not be duplicated
elsewhere.
MMV provided us with an outstanding
mentor, Mike Witty. His and David’s
input have been invaluable for me and
all the postdocs1 here. Between David,
Mike, and now Leslie Street, who joined
H3-D in April 2012 as Head of Medici-
nal Chemistry, we benefit from 80 years’
worth of combined pharma industry
experience!
MMV also provides sustained funding,
which does not always happen for
academic projects. This enables us to
build and maintain the talent needed
to progress the project. Of course, it all
depends on us meeting project goals
and milestones and all going well at the
ESAC annual review.
MMV’s contribution to the future of drug
discovery in Africa is immeasurable – it
has set in motion a virtuous circle of
capacity building at UCT that can now
not only be used for malaria but also for
other diseases, like TB. It means that
African scientists have a chance to de-
velop their careers at home rather than
abroad.
Plus the project is helping to counter
Afro-pessimism. It’s the first time a drug
researched on African soil has pro-
gressed this far. Once you have shown
you can do something never done
before it sets a precedent.
A novel antimalarial compound
from the aminopyridine class,
MMV390048, becomes the first
researched in Africa to enter preclinical
development. In recognition of the po-
tential of this exciting compound, the
University of Cape Town (UCT) team
has been awarded MMV Project of the
Year 2012.
1 Post-doctoral researchers.
MMV Project Directors:
Drs David Waterson and Cristina Donini
Partners: University of Cape Town, South
University, Australia
MMV390048 – boosting African research
Malaria-infected red blood cell courtesy
of National Institute of Allergy and
Infectious Diseases, USA
31
Dr Michael Witty
Member of MMV’s ESAC and pro-
ject mentor for MMV390048, Mike
has more than 30 years of phar-
maceutical research experience.
Since retiring in 2008, he provides
support mostly to not-for-profit
research organizations, like MMV.
What was your role as project
mentor?
My role was three-fold – strategic, tac-
tical and personal. First, to assist the
development of the project I brought
my own creativity, knowledge and ex-
perience of the malaria field. Second,
I helped to provide a link between the
team and ESAC to ensure alignment with
MMV’s Target Product Profiles and Pro-
gression Criteria. Third, I helped where
I could in terms of team and project
management.
Why is this project important to
you?
I have contributed to a number of suc-
cessful drug and vaccine R&D projects
over a long career but this one has the
potential to relieve suffering for millions
of people.
I have been involved in this project
since its outset, initially prioritizing and
optimiz ing the hits from screening of the
Biofocus libraries at the Eskitis Institute
and now overseeing the work to move
the compound into man. I have invested
a lot of myself in the work, as have Kelly
and his team.
The project is very important to the UCT
team, as it has the potential to deliver the
first antimalarial drug researched in Africa.
Why has this project been
successful?
Traditionally, academic groups are
slower than industry teams in progress-
ing hits into development, owing to
other demands on their time, such as
teaching, and grant and article writing.
From the outset, Kelly has been willing
to embrace the industry approach in an
academic setting. His team has been
focused on selecting and progressing
the best compound for clinical develop-
ment. Creating H3-D2, Africa’s first inte-
grated drug discovery and development
centre, demonstrates this commitment.
Kelly has also been very proactive in
seeking funding for equipment and
bringing in expertise. Through the MMV
network, we have been able to access
the expertise of world-class talent such
as Drs Sue Charman (Monash Univer-
sity) and Sergio Wittlin (Swiss TPH)
among others.
What has the experience taught
you?
The lessons are not new but worth
repeating:
Commitment, focus and collabora-
tion are critical to team success.
Visions can be achieved by
hard-working, enthusiastic and
committed leaders.
MMV’s partnership model can
achieve success where the indi-
vidual pharmaceutical companies
have fallen short.
There is as much satisfaction
in helping others to succeed as
succeeding oneself.
Retirement can be even more
satisfying, productive and fun than
working full-time!
Associate Director,
Translational Medicine,
MMV, took over as
Project Director in
July 2012, when
MMV390048 was
selected as a candidate.
What is exciting about
MMV390048?
MMV390048 is potent against the blood
stage of malaria – it can completely cure
animal models of malaria in a single dose.
This result is outstanding and noteworthy
since drugs such as the artemisinins and
chloroquine do not achieve this. It sug-
gests MMV390048 could become part of a
single-dose cure in humans.
Moreover, the compound also has activity
against other stages of the lifecycle and
all known resistant strains of the parasite,
suggesting a role in malaria control, trans-
mission blocking and eradication.
What are the next steps in develop-
ing the molecule?
The preclinical work is underway. This in-
cludes manufacturing more compounds,
assessing the stability of the solid drug
and regulatory safety studies. So far,
MMV390048 appears well tolerated and
promises real clinical benefit, although
more definitive data is required. Planning
for success, the next step will be a Phase I
trial in healthy volunteers expected to start
in 2014 in South Africa.
2 University of Cape Town Drug Discovery and Development Centre: www.h3d.co.za
Charman, Yassir Younis, Karen White, David Waterson,
Michael Witty & Aloysius Nchinda
Douelle & Claire Le Manach
Dr Cristina Donini
32
Medicines for Malaria Venture (MMV)
receives funding and support from
government agencies, private foundations,
international organizations, corporate
foundations and private individuals (Figure 1).
These funds are used to finance the MMV
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 specific, targeted
access and product management (APM)
interventions to help ensure that vulnerable
populations in malaria-endemic countries can
access new malaria medicines.
As a not-for-profit Swiss foundation set up
under statutes dated 15 November 1999, MMV
is exempt from cantonal and federal taxes and is
the equivalent of an exempt organization within
the meaning of 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 – representing an estimated additional
contribution from Switzerland to MMV of up to
CHF 1 million per annum.
Portfolio funding
Unfavourable exchange rates and the
prolonged effects of the global economic
downturn continued to have an impact on
financial operations throughout 2012. It
was a challenging and eventful year where
prudent financial management involved careful
negotiation of contractual agreements and
increased in-kind contributions from partners.
Nevertheless, thanks to dynamic scientific and
financial management coupled with proactive
fundraising, healthy progress was ensured for
the full R&D and APM portfolio.
MMV’s drug R&D activity and corresponding
expenditure increased considerably in 2012
to United States Dollars (USD) 60.8 million
compared to USD 40.3 million in 2011.
Overall expenditure of USD 74.9 million rose
significantly by 37% compared with USD 54.7
million in 2011, mainly owing to a one-time USD
9.7 million R&D supplement grant received
from the UK Department for International
Development (DFID), whereas expenditure on
APM decreased slightly from USD 5.6 million in
2011 to USD 4.9 million in 2012.
Ongoing efforts to secure supplementary funding
brought new commitments amounting to a total
of USD 18.5 million from the Swiss Agency for
Development and Cooperation (SDC), the United
States Agency for International Development
(USAID) and the ExxonMobil Foundation.
Since its foundation in 1999, MMV has spent
USD 496 million to build the world’s largest
R&D portfolio of new and innovative antimalarial
medicines, with four that have already been
launched. Our business plan estimates needing
a minimum of USD 345 million over the 2013–
2018 period to sustain this work. With USD 90
million now in hand (cash brought forward to
2013 and outstanding committed pledges as
of the end of 2012), progress has been made.
Even so, there is currently a shortfall from 2013
onwards. MMV has several pending proposals
to donors and is also continuing to expand its
External Relations, Fundraising and Advocacy
capacity to close this gap.
6 Financial viewFinancial year to 31 December 2012
Figure 1. Funding from foundation to 2017 as of December 2012
Total received/pledged: USD 579.7 million
Bill & Melinda Gates Foundation
UK DFID
USAID
National Institutes of Health (NIH)
Wellcome Trust
Irish Aid
Netherlands Minister Devt. Co-operation
Swiss Government SDC
Spanish Agency for International Development
World Bank
Rockefeller Foundation
ExxonMobil Foundation
Newcrest Mining Limited
WHO/RBM
Individual donors
EU CRIMALDDI
33
Details
Income of MMV
2012 USD 57,984,195
2011 USD 67,285,068
2010 USD 58,122,675
2009 USD 42,180,117
2008 USD 53,953,831
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
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
Auditing of MMV’s accounts is conducted
annually by KPMG. 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. Interest income
on investments improved in 2012 to USD
294,167 as compared to 2011 (USD 96,338).
The Foreign Exchange Reserve, created in 2003
to hedge against adverse fluctuations in future
years, increased in 2012 to USD 1,148,686 due
to an exchange gain of USD 116,608, mainly as
a result of USD exchange rate volatility against
CHF, Euro (EUR) and the UK Pound (GBP) and
vigilant foreign exchange management.
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
2012.
Donations and pledges 2012 (see Note 6)
Cash donations received in the bank amounted
to a total of USD 55,950,282 with income
recognized in the previous year (2011) of USD
28,078, income deferred from the previous year
(2011) of USD 2,873,734 and income deferred
to the following year (2013) of USD 1,550,716.
Current 2012 income, to be received in early
2013 amounted to USD 375,419. Income of
USD 112,976 was recognized from MMV North
America Inc.
Management and administration
Management and administration cost increases
were kept in check during 2012. MMV’s staff
headcount went up from 51 to 54. This addition
to our staff pool will help build our capacity
for the future. The ratio of management and
administration expenditure to overall spending
decreased to 7.8% compared with 9.6% in 2011,
10.7% in 2010, 9.15% in 2009, 10.6% in 2008,
9.7% in 2007, 6.8% in 2006 and 11.1% in 2005.
Financial year ahead to December 2013
MMV operates in a complex multi-currency
environment. The bulk of donations are received
in USD, although other currencies are sometimes
involved. 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 Swiss Francs (CHF). The resulting exposure
or exchange risk is hedged, according to the
budget in January and at regular intervals over
the year, to provide a nominal fixed average USD/
CHF budget rate for the period. The accounts
are kept in US dollars.
Figure 2. MMV expenditure 2012
Total: USD 74.9 million
Financial year to 31 December 2012
6 | Financial view
34
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.
Focus on sustainability: R&D and APM
In 2012, MMV continued to prepare scale-up and
launch activities to ensure access to medicines
emerging from its pipeline. These activities will
enable a ‘downstream’ extension of the public–
private partnership model underpinning MMV’s
overarching goal to achieve major health impact
from its medicines. Moreover, in the new context
of malaria elimination/eradication, a second and
critical series of investments are now urgently
needed to spur R&D for the next generation of
antimalarial drugs designed specifically to meet
that goal.
Although fundraising remains successful and
significant additional funds were sourced in
2012, major fundraising efforts will be required
in 2013 and even more in 2014 and beyond,
as MMV strives to meet the projected financial
requirements of its growing portfolio.
Financial modelling
The long-term financial projections for future
MMV overall spending over 2013–2018 is USD
345 million. This figure represents a mixture of
R&D, product launch and APM-related spending,
including much needed innovation in treatments
for malaria in pregnancy, P. vivax malaria,
transmission blocking and other technologies for
elimination/eradication.
Since its foundation, MMV has been granted
multi-year pledges of funding for its R&D portfolio,
notably from the Bill & Melinda Gates Foundation,
DFID, the Swiss Agency for Development and
Cooperation, Irish Aid, the Netherlands Minister for
Development Cooperation, the Spanish Agency
for International Development, the Rockefeller
Foundation, the United States Agency for
International Development (USAID), the National
Institutes of Health (NIH), ExxonMobil Foundation,
BHP Billiton, Newcrest Mining Limited and the
Wellcome Trust.
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 (May
2013).
Financial tables
The financial tables and notes that follow
are extracted from the International Financial
Reporting Standards compliant accounts.
0
10
20
30
40
50
60
70
80
90
100
US
D in
mill
ions
2000 2002 2003 2004 2007 2008 2009 2011 2012 2013 2014 2015 2016 2018201720052001 2006 2010
Carry-over year/year
Annual income/pledged
Total expenditure
Figure 3. MMV income and expenditure to date and scenario 2013–2018
35
LIABILITIES AND CAPITAL & RESERVES Notes 2012 (USD) 2011 (USD)
CURRENT LIABILITIES
Accrued R&D Commitments 7 4 224 660 4 102 823
Accrued APM Commitments 7 252 936 936 598
Deferred Income 6 1 550 716 2 873 734
Other Creditors 543 106 535 829
Accrued Expenses 1 890 845 1 600 508
Short-Term Provisions 5 413 241 401 184
TOTAL CURRENT LIABILITIES 8 875 504 10 450 676
NON-CURRENT LIABILITIES
Post-Retirement Obligation 8 – –
TOTAL NON-CURRENT LIABILITIES – –
CAPITAL & RESERVES
Foundation Capital 4 000 000 4 000 000
Operations Reserve 18 341 888 34 973 491
Foreign Exchange Reserve 1 148 686 1 032 078
TOTAL CAPITAL & RESERVES 23 490 574 40 005 569
TOTAL LIABILITIES AND CAPITAL & RESERVES 32 366 078 50 456 245
ASSETS Notes 2012 (USD) 2011 (USD)
CURRENT ASSETS
Cash and Cash Equivalents 3 28 412 564 47 424 120
Donations Receivable 6 375 419 28 078
Project Reimbursements Receivable 1 525 374 466
Accounts Receivable 50 473 33 963
Tax Receivable 39 484 27 875
Prepaids 609 996 254 600
Prepaid R&D Commitments 7 1 755 076 1 672 598
Prepaid APM Commitments 7 461 627 30 000
TOTAL CURRENT ASSETS 31 706 164 49 845 700
LONG-TERM ASSETS
Guarantees 15 184 608 129 503
Employee Benefits 8 163 875 352 902
Fixed Assets, Net 4 311 431 128 140
TOTAL LONG-TERM ASSETS 659 914 610 545
TOTAL ASSETS 32 366 078 50 456 245
MMV CONSOLIDATED STATEMENT OF FINANCIAL POSITION AT 31 DECEMBER 2012
6 | Financial view
36
RESULT FROM OPERATING ACTIVITIES (16 890 417) 12 546 530
Interest Income 294 167 96 338
Financial Expense (35 353) (26 187)
Net Financial Income 258 814 70 151
(LOSS)/SURPLUS FOR THE PERIOD (16 631 603) 12 616 681
OTHER COMPREHENSIVE INCOME
Foreign Currency Translation Differences for Foreign Operations 10 116 608 86 059
Other Comprehensive Income for the Period 116 608 86 059
TOTAL COMPREHENSIVE INCOME FOR THE PERIOD (16 514 995) 12 702 740
ALLOCATIONS
Transfer (to)/from Operations Reserve 16 631 603 (12 616 681)
Transfer (to)/from Donor Restricted Reserve – –
Transfer (to)/from Foreign Exchange Reserve (116 608) (86 059)
16 514 995 (12 702 740)
EXPENDITURE Notes 2012 (USD) 2011 (USD)
RESEARCH & DEVELOPMENT EXPENDITURE
Project Grants 7 48 406 607 30 623 652
Project-Related Variable Expenditure 7 11 881 862 9 368 587
Expert Scientific Advisory Council Expenses 468 060 337 766
TOTAL RESEARCH & DEVELOPMENT EXPENDITURE 60 756 529 40 330 005
ACCESS EXPENDITURE
Project Expenditure 7 3 056 423 3 638 279
Access-Related Variable Expenditure 1 779 486 1 795 744
Access & Product Management Uganda Office – 2 184
Access & Product Management Advisory Committee 79 956 135 466
TOTAL ACCESS EXPENDITURE 4 915 865 5 571 673
EXTERNAL RELATIONS AND ADVOCACY (ER&A) EXPENDITURE
ER&A-Related Variable Expenditure 2 501 376 2 421 438
Fundraising 227 532 476 597
Communications 242 703 272 842
TOTAL EXTERNAL RELATIONS & ADVOCACY EXPENDITURE 2 971 611 3 170 877
FOUNDATION BOARD & STAKEHOLDER EXPENSES 13 373 634 392 918
GENERAL AND ADMINISTRATION EXPENSES
Staff-Related Benefits/Compensation 8 3 596 570 3 266 792
Office and Occupancy 11 1 189 424 1 113 051
Travel Expenses 55 642 49 606
Professional and Legal Fees 294 851 218 577
Training Education and Journals 67 562 32 967
IT Expenses 397 866 405 455
Depreciation 4 113 070 119 019
Other 127 109 67 598
TOTAL GENERAL ADMINISTRATION EXPENSES 5 842 094 5 273 065
OTHER EXPENSES 14 879 –
TOTAL EXPENDITURE 74 874 612 54 738 538
INCOME Notes 2012 (USD) 2011 (USD)
DONATION REVENUES
Private Foundations & Individual Donors 31 712 484 44 936 810
UN Agencies – 440 000
Government Agencies 24 519 306 20 985 401
Corporates & Corporate Foundations 1 388 851 798 000
TOTAL DONATIONS RECEIVED 6 57 620 641 67 160 211
OTHER INCOME
TOTAL OTHER INCOME 9 363 554 124 857
TOTAL INCOME 57 984 195 67 285 068
MMV CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME FOR THE PERIOD
ENDED 31 DECEMBER 2012
37
Notes 2012 (USD) 2011 (USD)
SURPLUS FOR THE YEAR (16 514 995) 12 702 740
Adjustments for:
Increase/(Decrease) in Provisions 5 12 057 5 257
Depreciation 4 113 070 119 019
OPERATING RESULT BEFORE WORKING CAPITAL CHANGES (16 389 868) 12 827 016
CASH FLOWS FROM OPERATING ACTIVITY
Decrease in Donations Receivable (347 341) 303 479
(Increase)/Decrease in Project Balance Reimbursements 372 941 (288 269)
Decrease in Accounts Receivable (16 577) 12 030
(Increase)/Decrease in Tax Receivable (10 139) (11 158)
(Increase)/Decrease in Project-Related Prepaid Expenses 7 (514 105) (1 221 497)
(Increase) in Prepaid Expenses (355 396) (147 464)
Increase in Accrued R&D Commitments 7 121 837 2 264 211
(Decrease)/Increase in Accrued APM Commitments 7 (683 662) 568 986
Increase/(Decrease) in Deferred Income 6 (1 344 848) 2 873 734
Increase/(Decrease) in Other Creditors 7 089 145 352
(Decrease)/Increase in Accrued Expenses 291 058 (175 861)
(Increase)/Decrease in Employee Benefits 8 189 027 (558 853)
Unrealized foreign currency (gain)/loss (30 455) 158 105
CASH FLOW RESULTING FROM OPERATING ACTIVITY (2 320 571) 3 922 795
CASH FLOWS FROM INVESTMENT ACTIVITY
Increase in Guarantees (47 612) (21 257)
Increase in Fixed Assets 4 (296 361) (71 249)
CASH FLOW RESULTING FROM INVESTMENT ACTIVITY (343 973) (92 506)
NET INCREASE/(DECREASE) OF CASH AND CASH EQUIVALENTS (19 054 412) 16 657 305
Cash and Cash Equivalents at Beginning of Year 47 424 120 30 879 654
Effect of Exchange Rate Fluctuations on Cash Held 42 856 (112 839)
Cash and Cash Equivalents at End of Year 28 412 564 47 424 120
MMV CONSOLIDATED STATEMENT OF CASH FLOW AT 31 DECEMBER 2012
Foreign Total
Foundation Operations Exchange Capital and
Capital Reserve Reserve Revenues
(USD) (USD) (USD) (USD)
Balance at 1 January 2011 4 000 000 22 356 810 946 019 27 302 829
TOTAL COMPREHENSIVE INCOME FOR THE PERIOD
Gain for the Period – 12 616 681 – 12 616 681
OTHER COMPREHENSIVE INCOME
Foreign Currency Translation Differences for Foreign Operations – – 86 059 86 059
BALANCE AT 31 DECEMBER 2011 4 000 000 34 973 491 1 032 078 40 005 569
TOTAL COMPREHENSIVE INCOME FOR THE PERIOD
Gain for the Period – (16 631 603) – (16 631 603)
OTHER COMPREHENSIVE INCOME
Foreign Currency Translation Differences for Foreign Operations – – 116 608 116 608
BALANCE AT 31 DECEMBER 2012 4 000 000 18 341 888 1 148 686 23 490 574
MMV CONSOLIDATED STATEMENT OF CHANGES IN EQUITY
6 | Financial view
38
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
8 senior managers.
With its head office in Geneva, the aim of MMV
is to bring public and private sector partners to-
gether to fund, and provide managerial and logis-
tical support, for the discovery and development
of new medicines for the treatment and preven-
tion of malaria. The products should be afford-
able and appropriate for use by populations in
developing countries.
As with all Swiss foundations, Medicines for Ma-
laria 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 fi-
nancial statements are set out below.
Statement of compliance
The consolidated financial statements were ap-
proved for issue by the MMV Board on 28 March
2013.
The consolidated financial statements comply with
the accounting and reporting requirements of the
International Financial Reporting Standards (IFRS)
as issued by the International Accounting Stan-
dards Board (IASB).
The consolidated financial statements have been
prepared on the historical cost basis, except where
a standard requires a different measurement basis.
Basis of preparation
The consolidated financial statements are pre-
sented in USD, 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 IFRS requires man-
agement to make judgements, estimates and
assumptions that affect the application of poli-
cies and reported amounts of assets and liabili-
ties, income and expenditure. The estimates and
associated assumptions are based on historical
experience and various other factors that are be-
lieved 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 oth-
er sources. Actual results may differ from these
estimates. If in the future such estimates and as-
sumptions, which are based on management’s
best judgement at the date of the consolidated
financial statements, deviate from the actual cir-
cumstances, the original estimates and assump-
tions will be modified as appropriate in the year in
which the circumstances change.
Judgements made by management in the appli-
cation of IFRS 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.
The accounting policies set out below have been
applied consistently to all periods presented in
these consolidated financial statements.
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 mea-
sured in terms of historical cost in a foreign cur-
rency are translated using the exchange rate at
the date of the transaction.
The following exchange rates were used at
year-end:
2012
1 CHF = USD 1.0925
1 EUR = USD 1.3184
1 GBP = USD 1.6254
1 AUD = USD 1.0382
2011
1 CHF = USD 1.0694
1 EUR = USD 1.2982
1 GBP = USD 1.5541
1 AUD = USD 1.0252
Cash and cash equivalents
Cash and cash equivalents comprise cash
balances and short-term money market depos-
its with original maturities of 3 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
the 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
Financial Position date to determine whether
there is an indication of impairment. If any such
indication exists, the asset’s recoverable amount
is estimated. An impairment loss is recognized
in the Consolidated Statement of Comprehen-
sive Income whenever the carrying amount of an
asset exceeds its recoverable amount.
The recoverable amount of an asset is the great-
er 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 of
money and the risks specific to the asset.
Provisions
A provision is recognized in the Consolidated
Statement 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.
MMV maintains a retirement plan for its employ-
ees. This plan is considered as a defined benefit
plan under IAS 19. The contributions are paid 75%
by the employer and 25% by the employees.
MMV’s obligations towards the defined benefit
pension plan and the annual cost recognized in
the Consolidated Statement of Comprehensive In-
come is determined by independent actuaries us-
ing the projected unit credit method. Pension costs
primarily represent the increase in the actuarial
present value of the theoretical obligation for pro-
jected pension benefits based on employee service
during the year and the interest on this obligation in
respect of employee service in previous years, net
of the expected future return on plan assets.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS AS OF 31 DECEMBER 2012
39
Foundation capital
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. Under exceptional
circumstances, Foundation capital together with
the residual operations reserve serves to main-
tain the viability of the organization, for 6 months,
until other funding sources can be found.
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.
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.
Operations reserve
The accumulated Operations Reserve represents
excess of income over expenditure since the in-
ception of MMV and is available to be utilized for
future operation and project funding costs as the
rapidly evolving R&D project pipeline dictates.
Foreign exchange reserve
Expenditure for operational costs in Geneva is de-
nominated in CHF. The Foreign Exchange Reserve
serves as a segregated fund for use to reduce the
impact of future adverse currency fluctuations.
Interest income and financial expense
Interest income and financial expense comprise
interest on funds invested and bank charges.
Research and development expenditure
Expenditure and grants allocated for R&D ac-
tivities undertaken with the prospect of gaining
new scientific or technical knowledge and under-
standing 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 un-
der current liabilities. Expenses paid before year
end for the following period are recorded as Pre-
paid 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
immunities – effective as of 1 January 2011.
The principal advantages for MMV as a Swiss
foundation with Other International Organization
status are:
Exoneration from all direct and indirect federal,
cantonal and communal taxes (this was origi-
nally acquired by decree with the Geneva Can-
tonal and Swiss federal authorities, but now
formalized directly with the Swiss government
within the accord)
Exoneration from VAT on all goods and ser-
vices acquired for the sole use of the founda-
tion 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.).
In accordance with SIC 12 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 2012:
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 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.
R&D expenditure – MMV’s R&D expenditure
is generally not direct expenditure, but is in
the form of grants and contracts with external
parties who perform certain tasks at its 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
R&D timing and execution are often different
from the original plans. These factors lead to
subjectivity in the timing and recognition of R&D
expenditure.
Changes in accounting policies
MMV has applied the revised IFRS and IAS as
from 1 January 2011 onwards. These changes
have been applied in accordance with the new
standards, none of which had a material impact
on MMV’s consolidated financial statements.
Certain comparative amounts have been reclassi-
fied to conform to the current year’s presentation.
New standards and interpretations
not yet adopted
The following new and revised Standards and
Interpretations have been issued, but are not
yet effective. They have not been applied early
in these consolidated financial statements. Their
impact on the consolidated financial statements
of MMV has not yet been systematically
analysed. However, a preliminary assessment
has been conducted by Group Management
and the expected impact of each Standard and
Interpretation is presented overleaf.
Country United States of America
Name and domicile MMV, North America, Inc.
Functional currency USD
% controlled by MMV N/A
Direct/indirect N/A
6 | Financial view
40
Fixtures and Office Computers and
Installations Furniture Equipment Total
2012 (USD) (USD) (USD) (USD)
COST
At 1 January 2012 303 672 358 448 750 044 1 412 164
Additions 190 200 50 970 55 190 296 361
Disposals – (855) (49 220) (50 105)
At 31 December 2012 493 873 408 534 756 014 1 658 421
ACCUMULATED DEPRECIATION
At 1 January 2012 302 979 299 979 681 067 1 284 025
Charge for the year 23 052 35 969 54 049 113 070
Disposals – (885) (49 219) (50 104)
At 31 December 2012 326 031 335 063 685 896 1 346 990 NET BOOK VALUE AT 31 DECEMBER 2012 167 842 73 471 70 118 311 431
Fixtures and Office Computers and
Installations Furniture Equipment Total
2011 (USD) (USD) (USD) (USD)
COST
At 1 January 2011 303 672 334 578 707 953 1 346 203
Additions – 24 421 47 158 71 579
Disposals – (551) (5 067) (5 618)
At 31 December 2011 303 672 358 448 750 044 1 412 164
ACCUMULATED DEPRECIATION
At 1 January 2011 302 286 269 942 598 065 1 170 293
Charge for the year 693 30 257 88 069 119 019
Disposals – (220) (5 067) (5 287)
At 31 December 2011 302 979 299 979 681 067 1 284 025
NET BOOK VALUE AT 31 DECEMBER 2010 693 58 470 68 977 128 140
4. FIXED ASSETS
The effective rates on deposits have moved within the following ranges:
2012 2011
Low % High % Low % High %
US Dollar (USD) 0.00 0.20 0.10 0.20
Swiss Franc (CHF) 0.05 0.15 0.125 0.20
British Pound (GBP) 0.00 0.20 0.20 0.20
Euro (EUR) 0.05 0.25 0.20 0.50
Australian Dollar (AUD) 0.00 3.60 0.00 3.60
At 31 December 2012 (USD) At 31 December 2011 (USD)
Cash 2 570 1 813
Bank Balances 26 409 994 45 422 307
Money Market Deposits (Maturity less than 3 Months) 2 000 000 2 000 000
TOTAL CASH AND CASH EQUIVALENTS 28 412 564 47 424 120
3. CASH AND CASH EQUIVALENTS
Effective date Planned application by MMV and impact
New Standards or Interpretations
IFRS 10 Consolidated Financial Statements 1 January 2013Reporting year 2013 – No significant impact for MMV (no change in the consolidation scope)
IFRS 11 Joint Arrangements 1 January 2013 N/A
IFRS 12 Disclosure of Interests in Other Entities 1 January 2013 N/A
IFRS 13 Fair Value Measurement 1 January 2013 Reporting year 2013 – No significant impact for MMV
IFRIC 20 Stripping Costs in the Production Phase of a Surface Mine 1 January 2013 N/A
IFRS 9 Financial Instruments and related amendments to IFRS 7 regarding transition 1 January 2015 Reporting year 2015 – No significant impact for MMV
Revisions and Amendments of Standards and Interpretations
Presentation of Items of Other Comprehensive Income (Amendments to IAS 1) 1 July 2012 Reporting year 2013 – Impact in correlation with IAS 19R
IAS 19 Employee Benefits (amended 2011) 1 January 2013Reporting year 2013 – MMV should recognize the full actuarial result through the Other Comprehensive Income instead of using the Corridor Method
IAS 27 Separate Financial Statements (2011) 1 January 2013 N/A
IAS 28 Investments in Associates and Joint Ventures (2011) 1 January 2013 N/A
Disclosures: Offsetting Financial Assets and Financial Liabilities (Amendments to IFRS 7) 1 January 2013 Reporting year 2013 – No significant impact for MMV
Offsetting Financial Assets and Financial Liabilities (Amendments to IAS 32) 1 January 2014 N/A
Investment Entities (Amendments to IFRS 10, IFRS 12 and IAS 27) 1 January 2014 N/A
Government Loans (Amendments to IFRS 1) 1 January 2013 N/A
Table 2. New and revised standards and interpretations for 2012.
41
5. PROVISIONS
Unused Vacation Bad debt Total
Reserve provision Provisions
(USD) (USD)
Balance at 31 December 2011 395 927 – 395 927
Use / Release 2011 (355 628) – (355 628)
Allocation for the Year 360 885 – 360 885
Balance at 31 December 2012 401 084 – 401 184
Use / Release 2012 (401 084) – (401 084)
Allocation for the Year 398 362 14 879 413 241
BALANCE AT 31 DECEMBER 2011 398 362 14 879 413 241
6. DONATIONS
Below is a summary of donations received or committed during 2012:
Cash Income Recognized Income Deferred Income Deferred Current Year Total Income
Received 2012 During Previous from Previous to Following Income to be as per
Year Year Year Received Statement CI
(USD) (USD) (USD) (USD) (USD) (USD)
Bill & Melinda Gates Foundation 30 000 000 – – – – 30 000 000 Wellcome Trust 1 600 000 – – – – 1 600 000 Swiss Government (DEZA/SDC) 1 727 072 – – – – 1 727 072 Swiss Government SfL* (DEZA/SDC) 267 275 – – – – 267 275 UK Government (DFID) 13 861 602 – 2 577 554 – – 16 439 156 Irish Aid 2 546 610 – – (1 318 400) – 1 228 210 US Government (USAID) 3 000 000 – – – – 3 000 000 Nat. Inst. Health (NIH) 1 793 729 – 296 180 (232 316) – 1 857 593 European Union (CRIMALDDI) 24 078 (24 078) – – – – ExxonMobil Foundation 500 000 – – – – 500 000 Newcrest Mining Limited 513 432 – – – 371 419 884 851
Individual donors 116 484 (4 000) – – 4 000 116 484
TOTAL RECEIVED 55 950 282 (28 078) 2 873 734 (1 550 716) 375 419 57 620 641
Of the total donations recognized in the Consolidated Statement of Comprehensive Income, USD 112,976 have been received through MMV, North America, Inc.
During the 2012 fiscal year, MMV North America Inc. granted MMV Switzerland USD 100,000 which were eliminated in the consolidation process.
*Funds specifically for SMS for Life
6 | Financial view
42
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Mala
ria B
ox
AD
ME
T 1
058 8
49
1 0
58 8
49
1 0
58 8
49
Med
icin
es
for
Mala
ria V
entu
re
25
Eva
luate
Dengue a
nd A
nti-
infla
mm
ato
ry A
ctiv
ity o
f M
ala
ria B
ox
Com
pounds
35 0
00
8 7
50
8 7
50
26 2
50
M
ed
icin
es
for
Mala
ria V
entu
re
26
Challe
nge G
rants
(15 x
US
D 5
0,0
00)
750 0
00
336 2
24
336 2
24
413 7
76
Med
icin
es
for
Mala
ria V
entu
re
Le
ad
Op
tim
iza
tio
n
3 1
35 5
61
3 1
34 4
65
2 9
85 3
67
149 0
98
1 0
96
27
Dih
ydro
oro
tate
Dehyd
rogenase
(D
HO
DH
) In
hib
itor
782 8
10
782 8
10
679 5
70
103 2
40
Univ
ers
ity o
f Te
xas
South
west
ern
Med
ical C
ente
r, M
onash
Univ
ers
ity, U
niv
ers
ity o
f W
ash
ingto
n
28
Anacor
Oxa
boro
les
595 5
13
595 5
13
595 0
00
513
Anacor
29
Quin
olo
ne for
Rad
ical C
ure
119 8
80
119 8
80
119 8
80
Univ
ers
ity o
f S
outh
Flo
rid
a
30
PfN
DH
2
400 4
95
400 4
95
400 4
95
Univ
ers
ity o
f Liv
erp
ool
31
Tetr
aoxa
ne
455 9
76
454 8
80
454 8
80
1 0
96
Univ
ers
ity o
f Liv
erp
ool
32
Cand
idate
Pro
filin
g
677 1
25
677 1
25
669 6
48
7 4
77
Med
icin
es
for
Mala
ria V
entu
re
33
Com
pound
Managem
ent
103 7
62
103 7
62
65 8
94
37 8
68
SP
EC
S
Pre
clin
ica
l D
eve
lop
me
nt
1 2
16 6
81
1 2
16 6
81
1 0
67 7
45
148 9
36
–
34
DS
M265-D
HO
DH
inhib
itors
1
061 2
75
1 0
61 2
75
913 1
57
148 1
18
Med
icin
es
for
Mala
ria V
entu
re (U
niv
ers
ity o
f Te
xas
South
west
ern
Med
ical C
ente
r, M
onash
Univ
ers
ity)
35
ELQ
-300
19 2
45
19 2
45
19 2
45
Med
icin
es
for
Mala
ria V
entu
re
36
21A
092
136 1
61
136 1
61
135 3
43
818
Med
icin
es
for
Mala
ria V
entu
re
Ph
ase
I
1 4
63 3
50
1 4
63 3
50
1 4
63 3
50
–
–
37
GN
F156
1 4
63 3
50
1 4
63 3
50
1 4
63 3
50
Nova
rtis
Inst
itite
for
Trop
ical D
isease
s P
te. Ltd
.
Ph
ase
II /
PO
C
8 9
02 8
10
8 9
02 8
10
7 6
73 2
91
1 2
29 5
19
–
38
OZ
439 D
eve
lop
ment
8 3
00 0
00
8 3
00 0
00
7 0
70 4
81
1 2
29 5
19
Med
icin
es
for
Mala
ria V
entu
re, (M
onash
Univ
ers
ity, S
wis
s TP
H, U
niv
ers
ity o
f N
eb
rask
a M
ed
ical
Cente
r)
39
KA
E609 N
ova
rtis
6
02 8
10
602 8
10
602 8
10
Nova
rtis
Inst
itute
for
Trop
ical D
isease
s P
te. Ltd
.
Ph
ase
III
1
653 0
91
1 6
53 0
91
1 4
43 1
73
209 9
17
–
40
Pyr
am
ax®
(p
yronarid
ine-a
rtesu
nate
) 1
645 2
91
1 6
45 2
91
1 4
35 3
73
209 9
17
Shin
Poong P
harm
aceutic
al C
o. Ltd
., U
niv
ers
ity o
f Io
wa
41
IM A
rthem
ete
r P
req
ualifi
catio
n 7
800
7 8
00
7 8
00
Guilin P
harm
aceutic
al (
Shanghai)
Co., L
td. (G
PS
C), IP
CA
7. P
RO
JE
CT
GR
AN
TS
43
Ph
ase
III
B/I
V
3 2
41 6
42
3 2
41 6
42
2 9
97 4
54
244 1
88
–
42
Coars
ucam
RC
I (A
S-A
Q)
139 0
17
139 0
17
139 0
17
Sanofi
43
Eura
rtesi
m® (d
ihyd
roart
em
isin
in-p
ipera
quin
e)
718 5
34
718 5
34
718 5
34
Sig
ma-T
au Ind
ust
rie F
arm
aceutic
he R
iunite
, Italy
44
Eura
rtesi
m® R
egis
trie
s 9
71 0
00
971 0
00
971 0
00
Sig
ma-T
au Ind
ust
rie F
arm
aceutic
he R
iunite
, Italy
45
IV A
rtesu
nate
1
700
1 7
00
1 7
00
Guilin P
harm
aceutic
al (
Shanghai)
Co., L
td. (G
PS
C), IP
CA
, TD
R
46
Longitu
din
al S
tud
y w
ith E
DC
TP
1
214 7
70
1 2
14 7
70
1 1
67 2
04
47 5
66
Mala
ria R
ese
arc
h a
nd
Tra
inin
g C
ente
r, U
niv
ers
ity o
f B
am
ako
47
AZ
-CQ
Challe
nge S
tud
y 1
96 6
22
196 6
22
–
196 6
22
Pfiz
er
Lim
ited
, Lond
on S
chool o
f H
ygie
ne &
Tro
pic
al M
ed
icin
e
Elim
ina
tio
n/E
rad
ica
tio
n
15 0
27 8
13
14 1
31 1
64
12 4
34 8
52
1 6
96 3
12
896 6
49
48
Chlo
roq
uin
e/A
zith
rom
ycin
IP
Tp
1 5
00 0
00
1 5
00 0
00
1 5
00 0
00
Pfiz
er
Lim
ited
, Lond
on S
chool o
f H
ygie
ne &
Tro
pic
al M
ed
icin
e, Q
ueensl
and
Inst
itute
of M
ed
ical
rese
arc
h Q
IMR
49
Coart
em
® D
isp
ers
ible
less
than 5
kg
590 1
04
590 1
04
420 9
44
169 1
60
Nova
rtis
Pharm
a A
G
50
Eura
rtesi
m® D
eve
lop
ment of P
aed
iatr
ic F
orm
ula
tion
1 0
54 2
86
1 0
54 2
86
1 0
54 2
86
Sig
ma-T
au Ind
ust
rie F
arm
aceutic
he R
iunite
, Italy
51
Pyr
am
ax®
(p
yronarid
ine-a
rtesu
nate
) in
P. vi
vax/
child
ren
145 1
66
145 1
66
141 9
96
3 1
70
Shin
Poong P
harm
aceutic
al C
o. Ltd
., U
niv
ers
ity o
f Io
wa
52
Pyr
am
ax®
(p
yronarid
ine-a
rtesu
nate
) S
achet
84 0
33
84 0
33
46 7
28
37 3
05
Shin
Poong P
harm
aceutic
al C
o. Ltd
., U
niv
ers
ity o
f Io
wa
53
Tafe
noq
uin
e 5
956 4
36
5 9
56 4
36
4 7
35 1
14
1 2
21 3
22
Gla
xoS
mith
Klin
e p
lc.
54
G6P
D D
iagnost
ic
102 7
55
102 7
55
52 7
55
50 0
00
Gla
xoS
mith
Klin
e p
lc., O
thers
55
Eura
rtesi
m® P
rim
aq
uin
e Inte
ractio
n S
tud
y 1
1 9
06
11 9
06
–
11 9
06
Mahid
ol-O
xford
Univ
ers
ity T
rop
ical M
ed
icin
e R
ese
arc
h U
nit
56
Pyr
am
ax®
Prim
aq
uin
e Inte
ractio
n S
tud
y 3
2 1
62
32 1
62
2 8
13
29 3
49
Mahid
ol-O
xford
Univ
ers
ity T
rop
ical M
ed
icin
e R
ese
arc
h U
nit
57
Viv
ax
Anti-
rela
pse
Clin
ical S
tud
y 7
21 8
52
247 3
95
247 3
95
474 4
57
Eijk
mann Inst
itute
, O
xford
Univ
ers
ity
58
MM
V390048
220 2
70
220 2
70
219 2
59
1 0
11
Univ
ers
ity o
f C
ap
e T
ow
n
59
GS
K Inse
cto
ry
594 0
64
594 0
64
594 0
64
Gla
xoS
mith
Klin
e p
lc.
60
P. v
ivax
Cultu
re S
yste
ms
and
Ass
ays
Deve
lop
ment
250 0
00
84 7
38
84 7
38
165 2
62
Univ
ers
ity o
f N
otr
e D
am
e
61
P. v
ivax
in v
itro R
esi
stance T
est
ing
57 3
94
57 3
94
57 3
94
Menzi
es,
School o
f M
ed
ical R
ese
arc
h
62
Deve
lop
ment of a L
iver
Sta
ge P
. vi
vax
in v
itro A
ssay
209 2
50
180 4
69
180 4
69
28 7
81
UC
San D
iego, S
chool o
f M
ed
icin
e
63
In v
ivo A
ssay
of C
om
pound
s w
ith H
em
oly
tic L
iab
ilitie
s 2
49 8
00
171 0
52
171 0
52
78 7
48
SU
NY
Up
state
Med
ical U
niv
ers
ity
64
Hig
h T
hro
ugh-p
ut B
lood
-sta
ge S
cre
ens
300 0
00
281 6
84
281 6
84
18 3
16
Esk
itis
Inst
itute
for
Cell
and
Mole
cula
r Thera
pie
s, G
riffi
th U
niv
ers
ity, Q
ueensl
and
Inst
itute
of M
ed
ical
Rese
arc
h
65
Mala
ria L
ab
Resi
stance M
uta
nts
Fid
ock
276 2
46
275 7
01
275 7
01
545
Univ
ers
ity o
f C
olu
mb
ia
66
Mala
ria L
ab
Resi
stance M
uta
nts
Fid
ock
270 0
00
270 0
00
270 0
00
Univ
ers
ity o
f C
olu
mb
ia
67
Gam
eto
cyt
e A
ssay
Deve
lop
ment and
Scre
en (st
age s
pecifi
c)
465 0
86
438 5
42
348 0
16
90 5
26
26 5
44
Imp
erial C
olle
ge L
ond
on
68
Gam
eto
cyt
e A
ssay
Deve
lop
ment and
Scre
en (st
age s
pecifi
c)
250 0
00
250 0
00
250 0
00
Imp
erial C
olle
ge L
ond
on
69
In v
itro D
rug S
ensi
tivity
of Im
port
ed
Mala
ria P
ara
site
s
165 6
30
165 6
30
165 1
54
476
Lond
on S
chool o
f H
ygie
ne &
Tro
pic
al M
ed
icin
e
70
Dru
g A
ssay
Pla
tform
for
inhib
ition o
f P.
falc
iparu
m T
ransm
issi
on S
tages
152 4
94
152 4
94
70 4
07
82 0
87
Rad
boud
Univ
ers
ity
71
Gam
eto
cyt
e p
latform
1 0
60 0
00
1 0
60 0
00
1 0
60 0
00
Esk
itis
Inst
itute
for
Cell
and
Mole
cula
r Thera
pie
s, G
riffi
th U
niv
ers
ity
72
chE
MB
L 9
9 9
60
99 9
60
99 9
60
chE
MB
L
73
Test
ing o
f C
om
pound
s on P
. yo
eilii L
iver
Sta
ge A
ssay
in v
itro
99 4
61
45 2
62
45 2
62
54 1
99
UC
San D
iego, S
chool o
f M
ed
icin
e
74
Deve
lop
ment of a P
. b
erg
hei u
HTS
Liv
er
Sta
ge A
ssay
and
Scre
enin
g o
f B
iofo
cus
Lib
rary
109 4
59
59 6
62
59 6
62
49 7
97
UC
San D
iego, S
chool o
f M
ed
icin
e
En
ab
lin
g T
ec
hn
olo
gie
s
4 5
81 9
58
4 5
64 5
58
4 3
84 3
45
180 2
13
17 4
00
75
GS
K T
ransl
atio
nal P
harm
acolo
gy
Gro
up
728 7
50
728 7
50
728 7
50
Gla
xoS
mith
Klin
e p
lc.
76
Sw
iss
TP
H 7
11 8
60
711 8
60
711 8
60
Sw
iss
TP
H
77
Monash
CD
CO
545 5
34
545 5
34
437 5
25
108 0
09
Monash
Univ
ers
ity
78
CR
O C
hem
istr
y 1
103 8
92
1 1
03 8
92
1 1
03 8
92
Syn
gene
79
PK
Analy
tical C
hem
istr
y 1
06 4
99
106 4
99
77 0
01
29 4
98
Sw
iss
Bio
quant
80
PK
/PD
Mod
elling
35 8
82
35 8
82
35 8
82
Med
icin
es
for
Mala
ria V
entu
re
81
The P
ilot H
um
an M
ala
ria C
halle
nge S
tud
y 1
184 2
02
1 1
84 2
02
1 1
84 2
02
Queensl
and
Inst
itute
of M
ed
ical R
ese
arc
h
82
Fie
ld Iso
late
s R
esi
stance
62 9
91
45 5
91
4 3
50
41 2
41
17 4
00
Med
icin
e for
Mala
ria V
entu
re, S
wis
s TP
H, C
entr
e S
uis
se d
e R
echerc
he S
cie
ntifi
que e
n C
ôte
d'Iv
oire
83
Syn
gene P
ara
sito
logy
102 3
47
102 3
47
100 8
82
1 4
65
Syn
gene
Te
rmin
ate
d P
roje
cts
9
6 6
20
96 6
20
95 9
18
702
84
(+) ery
thro
meflo
quin
e 4
05
405
405
Treague L
imite
d
85
Ihara
SS
J-1
83
(415)
(415)
(415)
Monash
Univ
ers
ity, S
wis
s TP
H, S
ynst
ar
86
Art
em
isone
7 5
95
7 5
95
6 8
93
702
Hong K
ong U
niv
ers
ity o
f S
cie
nce a
nd
Technolo
gy,
Med
icin
es
for
Mala
ria v
entu
re
87
Quin
olin
e M
eth
anols
11 5
39
11 5
39
11 5
39
Monash
Univ
ers
ity, U
niv
ers
ity o
f D
und
ee, U
niv
ers
ity o
f P
ittsb
urg
h
88
Dru
g R
ep
osi
tionin
g 4
482
4 4
82
4 4
82
St Jud
e C
hild
ren's
Rese
arc
h H
osp
ital;
Sw
iss
TP
H
89
ED
CTP
Longitu
din
al
73 0
14
73 0
14
73 0
14
ED
CTP
TO
TA
L50'1
61'6
82
48'4
06'6
07
44'1
81'9
46
4'2
24'6
60
1'7
55'0
76
44
6 | Financial view
Awarded 2012
(USD)
Final
Allocation
2012 (USD)
Paid 2012
(USD)
Related to
2012 paid in
2013 (USD)
Prepaid 2012
for 2013 (USD)
Project Partners
Introduction of New Product/ Oversee Launched Product
1 023 364 895 505 874 304 21 201 127 859
1 Policy Revision 98 740 98 740 95 400 3 339 – Medicines for Malaria Venture
2 Eurartesim® 72 281 72 281 72 281 – –Imperial College London, Sigma-Tau Industrie Farmaceutiche Riunite, Italy
3 Pyramax® 12 719 12 719 12 396 323 – Shin Poong Pharmaceutical Co. Ltd.
4 Injectable Artesunate – General 63 482 63 482 62 650 832 – Quintiles Inc.
5 Injectable Artesunate – Public Sector 610 312 495 931 495 931 – 114 382 Clinton Health Access Initiative, Swiss TPH
6 AZ-CQ 47 053 33 576 33 576 – 13 477 London School of Hygiene & Tropical Medicine, Pfizer
7 OZ439 20 734 20 734 18 803 1 931 – Medicines for Malaria Venture
8 AMFm 7 125 7 125 7 125 – – Health Action International, Africa
9Product Readiness – Packaging & Communications Materials
90 917 90 917 76 141 14 776 – Medicines for Malaria Venture
Input to R&D 621 408 287 640 183 013 104 627 333 768
10 Vivax – General 1 904 1 904 1 904 – – National Institute of Malaria Research
11Vivax – Market Research to Support Tafenoqine (GSK)
177 892 177 892 79 764 98 127 – GlaxoSmithKline Services
12 Vivax – Strategy Development (WHO) 226 565 – – – 226 565 World Health Organization
13India Comprehensive Case Management Pilot (NIMR)
215 047 107 844 101 344 6 500 107 203 India National Institute of Malaria Research
Gather & Generate Information 333 991 333 991 300 433 33 558 –
14 Market Intelligence – General 3 836 3 836 3 836 – – Medicines for Malaria Venture
15 Market Intelligence – Analytics and reports 144 423 144 423 144 423 – – IMS Health
16Market Volumes (market size & segmentation)
185 732 185 732 152 174 33 558 – IMS Health
ACT Scale-up Measure Availability, Stock-outs & Correct Case Management
728 844 728 844 658 514 70 330 –
17 SMS for Life – Kenya (KEMRI) 25 000 25 000 25 000 – – University of Oxford
18 SMS for Life – Tanzania 747 073 747 073 676 743 70 330 – Government of Tanzania
19 Rolling MIS 14 739 14 739 14 739 – – Liverpool School of Tropical Medicine
20 ALMA (57 969) (57 969) (57 969) – – African Leaders Malaria Alliance
Pricing Study 12 266 12 266 12 266 – –
21 Pricing Study Mozambique 12 266 12 266 12 266 – – Fundaçao Manhica
New Projects/Pilots 576 117 576 117 557 605 18 513 –
22 Interactive Map Tool – WHO GMP 11 296 11 296 11 296 – – World Health Organization
23CAPSS Final Data Collection, Analysis & Publications
8 700 8 700 8 700 – – Medicines for Malaria Venture
24 CAPSS+ Pilot Uganda 92 272 92 272 89 272 3 000 – PACE, Makerere University, Karolinska Institutet
25 Oilsearch 50 217 50 217 38 264 11 953 – Oil Search Health Foundation
26 Newcrest Alliance 413 632 413 632 410 072 3 560 – Montrose Int. LLP, Newcrest Mining Ltd
Access Events & Misc. Project Costs 222 061 222 061 217 354 4 707 –
27 Access – Stakeholders' Meeting 96 233 96 233 96 233 – – Medicines for Malaria Venture
28 Miscellaneous 125 828 125 828 121 121 4 707 – Medicines for Malaria Venture
TOTAL 3 518 050 3 056 423 2 803 487 252 936 461 627
v
7. PROJECT GRANTS (CONTINUED)
45
7. PROJECT GRANTS (CONTINUED)
Project grants represent the awards to the pro-
jects 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 meet-
ings/reviews, MMV scientific personnel compen-
sation and various scientific project consultan-
cies. Expenditure for this MMV support totalled
USD 11,881,862 and USD 9,368,587 in 2012 and
2011, 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
Salaries and related charges are included un-
der Project-Related Variable Expenditure, Ac-
cess-Related Variable Expenditure, External
Relations and Advocacy-Related Variable Ex-
penditure and Staff-Related Benefits/Compen-
sation in the Consolidated Statement of Com-
prehensive Income.
There were 54 employees at 31 December 2012
(2011: 51).
The pension plan covers all employees for death
and disability benefits. Cover for retirement ben-
efits begins in the year following each employ-
ee’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 bene-
fits are related to pensionable salary.
9. OTHER INCOME AND OTHER EXPENSES
10. FOREIGN CURRENCY TRANSLATION DIFFERENCES FOR FOREIGN OPERATIONS
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 2012, USD 813,192 were
recognized as an expense in the Consolidated Statement of Comprehensive Income in respect of
operating leases (2011: USD 679,330).
12. CONTINGENT ASSETS
As per current contractual agreements, and depending on satisfactory reporting to donors, contin-
gent assets related to donations are as follows:
OTHER INCOME 2012 (USD) 2011 (USD)
Project reimbursements (see Note 7) 11 597 80 766
Other 351 957 44 091
OTHER INCOME 363 554 124 857
OTHER EXPENSES 2012 (USD) 2011 (USD)
Allocation to bad-debt provision (14 879) –
OTHER EXPENSES (14 879) –
2012 (USD) 2011 (USD)
Less than 1 year 798 129 665 053
Between 1 and 5 years 3 165 703 415 079
More than 5 years 378 551 –
TOTAL 4 342 383 1 080 132
2012 (USD) 2011 (USD)
Less than 1 year 35 408 000 55 865 000
Between 1 and 5 years 34 077 000 53 074 000
More than 5 years – –
TOTAL 69 485 000 108 939 000
FOREIGN EXCHANGE GAIN/(LOSS) 2012 (USD) 2011 (USD)
Exchange gain from CHF (4 622) 44 934
Exchange gain from EUR 33 881 39 385
Exchange gain/(loss) from GBP 87 262 9 546
Exchange (loss) from UGX (33) (7 806)
Exchange gain from AUD 120 –
FOREIGN EXCHANGE GAIN/(LOSS) 116 608 86 059
6 | Financial view
46
”
13. RELATED PARTIES
MMV has a related party relationship with its
board members, executive officers and MMV
North America Inc.
In addition to their salaries, the organization also
contributes to a defined benefit pension plan for
all staff on a ratio of 75% employer and 25% em-
ployee.
Total remuneration expense is included in Proj-
ect-Related Variable Expenditure, Access-Re-
lated Variable Expenditure, External Relations
and Advocacy-Related Variable Expenditure and
Staff-Related Benefits/Compensation in the Con-
solidated Statement of Comprehensive Income.
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.
There were no loans to directors or executive of-
ficers for the years ended 31 December 2012 and
31 December 2011.
Some donors are represented on the foundation
council. Given the foregoing, these donors could
be considered as related parties. However, MMV
management considers that their presence on
the foundation council does not affect the nature
of the relationship between MMV and these do-
nors. Therefore, all MMV donors have been con-
sidered third parties.
14. FINANCIAL RISK MANAGEMENT
MMV has exposure to the following risks from its
use of financial instruments:
Credit risk
Liquidity risk
Market risk
This note presents information about MMV expo-
sure to each of the above risks and MMV object-
ives, policies and processes for measuring and
managing risks.
Credit risk
Credit risk is the risk of financial loss to MMV
if a counterparty to a financial instrument fails
to meet its contractual obligations, and arises
principally from exposure to MMV donors and
investments.
The philosophy underlining MMV financial man-
agement is that of prudent, conservative con-
trol, including an appropriate return on interim
treasury investments. Such investments serve
to maintain the value of the funds donated to
the foundation until such time as they are used
for the aims and objectives as defined in the
statutes.
MMV limits its exposure to credit risk by only
investing in bank time deposits and only with
counterparties that have a credit rating of at
least A from Standard & Poor’s or Moody’s.
At the Consolidated Statement of Financial Po-
sition date there were no significant concen-
trations of credit risk. The maximum exposure
to credit risk is represented by the carrying
amount of each financial asset in the Consol-
idated Statement of Financial Position, princi-
pally accounts receivable, short-term deposits
and cash.
As at 31 December 2012, there were no signif-
icant capital expenditure commitments. As a
condition to MMV’s business credit card rela-
tionship with its bank it has signed the bank’s
general terms and conditions agreement. This
agreement requires that MMV pledge a certain
amount of its assets to secure unpaid cred-
it card transactions for a total amount of CHF
300,000 (2011: CHF 300,000).
Liquidity risk
Liquidity risk is the risk that MMV will not be able
to meet its financial obligations as they fall due.
MMV’s approach to managing liquidity is to en-
sure, as far as possible, that it will always have
sufficient liquidity to meet its liabilities when due,
under both normal and stressed conditions, with-
out incurring unacceptable losses or risking dam-
age to MMV’s reputation.
Market risk
Market risk is the risk that changes in market
prices, such as foreign exchange rates and
interest rates, will affect MMV’s income or the
value of its holdings of financial instruments.
The objective of market risk management is to
manage and control market risk exposures within
acceptable parameters.
MMV is exposed to currency risk on donations
received, project grants and general and
administrative expenses that are denominated
in a currency other than the functional currency
(USD). These transactions are primarily
denominated in Euro, GBP and CHF. In respect
of monetary assets and liabilities denominated
in foreign currencies, MMV ensures that its net
exposure is kept to an acceptable level by buying
or selling foreign currencies at spot rates, when
necessary, to address short-term imbalances.
MMV also limits its exposure by settling
expenditures in foreign currencies with available
funds received from donors in the correspondent
currency. Moreover most of MMV expenditures
are settled in USD.
The needs of the organization to be covered
will normally be for the local expenses incurred.
Where possible, such needs will be covered
by spot or forward transactions. Forward
deals or options may be used to cover a future
exchange risk with regard to a pledged donation
to be received, significant account balances or
investments maintained in currencies other than
Swiss Francs or US dollars. Such operations may
be used only to hedge future exchange risks and
any form of speculation is prohibited.
Exposure to exchange rate risk is represented by
the carrying amount in foreign currencies of each
financial asset and liability in the Consolidated
Statement of Financial Position.
15. GUARANTEES
Guarantees concern office rental only and are
recoverable on vacating the premises subject to
the prevailing contracts.
16. 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 uncertain-
ties cannot be predicted with absolute certainty.
Management has concluded that provisions for
these risks are appropriate, and any adverse res-
olution of these uncertainties will not have a ma-
terial impact on the financial position or results of
the foundation.
17. 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.
47
REPORT OF THE AUDITORS TO THE BOARD OF MMV
48
Line 1 – left to right
Mr Ray Chambers, Chairman of MMV Board;
Special Envoy for Financing of the Health-
Related Millennium Development Goals;
Co-Founder of Malaria No More
Dr Pedro Alonso, Director, Barcelona Institute
for Global Health (ISGlobal), Hospital Clinic-
University of Barcelona, Spain
Dr Fatoumata Nafo-Traoré, Executive
Director, Roll Back Malaria Partnership,
Switzerland
Dr David Brandling-Bennett,
Deputy Director, Malaria, Bill & Melinda
Gates Foundation, USA
Line 2 – left to right
Mr Per Wold-Olsen, former President
of Human Health Intercontinental Region,
Merck & Co., Inc.; former Member of Merck’s
Management Committee, Denmark
Dr Ernest Darkoh, Chairman & Founding
Partner, BroadReach Healthcare, South Africa
Dr Robert Newman, Director, Global Malaria
Programme, World Health Organization,
Switzerland
Prof. Michael Ferguson,
Dean of Research and Professor of Molecular
Parasitology, University of Dundee, Scotland
Line 3 – left to right
Dr Dennis Schmatz, former Vice President,
Head of Tsukuba Research Institute, Merck-
Banyu Research Laboratories, Japan;
President of the Board of North America Inc.;
Co-Chairman MMV ESAC (Discovery)
Dr Winston Gutteridge, Former Chief,
Product R&D, Special Programme for
Research and Training in Tropical Diseases,
World Health Organization, Switzerland
Dr David Reddy, CEO, MMV, Switzerland
Dr Renee Van de Weerdt, Chief Child Health
& Emergency Response, UNICEF, USA
MMV Board
7 Behind the scenes
49
Dr Dennis Schmatz, President of the Board
of North America Inc.; Co-Chairman, MMV
ESAC (Discovery); former Vice-President, Head
of Tsukuba Research Institute, Merck-Banyu
Research Laboratories, Japan
Dr David Bowen, Independent Advisor, USA
Mr Ray Chambers, Chairman of MMV Board;
Special Envoy for Financing of the Health-
Related Millennium Development Goals;
Co-Founder of Malaria No More
Dr David Reddy, CEO, MMV, Switzerland
Ms Wendy Taylor, Director, Center for
Accelerating Innovation and Impact at USAID,
USA
Expert Scientific Advisory
Committee (ESAC)
Dr David McGibney, Co-Chairman MMV
ESAC (Development); Pharmaceutical
Research and Development Expert;
Consultant Pharmaceutical Physician
Dr Dennis Schmatz, Co-Chairman MMV
ESAC (Discovery); former Vice President,
Head of Tsukuba Research Institute, Merck-
Banyu Research Laboratories, Japan
Dr Salim Abdullah, Director, Ifakara Health
Institute, Tanzania
Dr Simon Campbell, Chemist; former Senior
Vice President, Worldwide Discovery and Medi-
cinal R&D, Europe, Pfizer; (founding Chairman
of ESAC 1999–2003)
Prof. Kelly Chibale, Founder and Director,
University of Cape Town, Drug Discovery and
Development Centre (H3-D), South Africa
Dr Robert Clay, Vice President Regulatory Af-
fairs, Oncology and Infection, AstraZeneca, UK
Dr Christine Clayton, Lecturer, Zentrum für
Molekulare Biologie, Heidelberg, Germany
Prof. Simon Croft, Professor of Parasitology
and Head of the Department of Infectious and
Tropical Diseases, LSHTM, UK
Prof. Umberto D’Alessandro, Theme Leader
Disease Control and Elimination, Medical
Research Council, Gambia*
Prof. Ogobara Doumbo, Director, Malaria
Research and Training Center, Bamako, Mali
Dr R Kip Guy, Department of Chemical
Biology and Therapeutics, St Jude Children’s
Research Hospital, USA
Dr Kasturi Haldar, Rev. Julius Nieuwland,
Professor of Biological Sciences, Director of
Center for Rare and Neglected Diseases,
University of Notre Dame, USA*
Dr Tran Tinh Hien, Deputy Director,
Hospital for Tropical Diseases, Ho Chi Minh
City, Vietnam
Dr Chantal Laburte, Clinician, Service
d’Urgence Sociale, Mulhouse, France
Dr Trevor Laird, Managing Director/Owner,
Scientific Update, UK
Dr Michael Makanga, Director South–South
Cooperation and Head of Africa Office, Euro-
pean and Developing Countries Clinical Trials
Partnership, South Africa
Dr Christine Manyando, Head of Public
Health Department, Tropical Diseases
Research Centre, Ndola, Zambia*
Prof. Wilbur Milhous, Associate Dean for
Research, College of Public Health, University
of South Florida, USA
Dr George K Mooney, KGM Pharma
Consulting LLC, USA*
Prof. François Nosten, MD; Director, Shoklo
Malaria Research Unit, part of the Wellcome
Trust–Mahidol–Oxford University Tropical
Medicine Research Programme, Thailand
Dr Bernhards Ogutu, Researcher, Kenya
Medical Research Institute, Kenya
Dr Paul Reider, Pharmaceutical Specialist and
Lecturer, Department of Chemistry, Princeton
Universtiy, USA
Dr David Roberts, Independent Scientific
Consultant, Congleton, UK
Prof. Carol Sibley, Department of Genome
Science, University of Washington, USA
Dr Peter Siegl, Director, Siegl Pharma
Consulting LLC, USA
Dr Per Sjoberg, Partner, Eureda, Sweden
Prof. Dennis Smith, former Vice President,
PGRD, Pfizer, UK
Prof. Terrie Taylor, MD and Distinguished
Professor, University of Michigan, USA
Dr Neena Valecha, MD; Director, National
Institute of Malaria Research, New Delhi, India
Prof. Steve Ward, Walter Myers Professor
of Parasitology, Liverpool School of Tropical
Medicine, UK
Dr Thomas Wellems, Chief, Laboratory of
Malaria and Vector Research, National Institute
of Allergy and Infectious Diseases, USA*
Dr Mike Witty, Chairman, Global Alliance for
Livestock Veterinary Medicines, UK
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; MD; Director, National Institute of
Malaria Research, New Delhi, India
Ms Valentina Buj, Health Specialist (Malaria
Partnerships), UNICEF, USA
Dr Elizabeth Chizema, Head of Research,
Ministry of Health, Zambia
Dr Alexander Dodoo, Head, Centre for
Tropical Clinical Pharmacology & Therapeutics
(CTCPT), Ghana
Dr Gunther Faber, Chairman, One Family
Health, UK
Dr Douglas Lungu, Hospital Director, Daeyang
Luke Hospital, Malawi
Dr David McGibney, Pharmaceutical
Research and Development Expert; Consultant
Pharmaceutical Physician; Co-Chairman MMV
ESAC (Development)
Prof. Ric Price, Associate Professor, Menzies
School of Health Research, Darwin, Australia
Ms Melanie Renshaw, Chief Technical
Advisor, African Leaders Malaria Alliance’s, USA
Dr Claude Emile Rwagacondo, Coordina-
tor of West Africa Roll Back Malaria Network
(WARN), Senegal
Dr GS Sonal, Additional Director and Head of
Malaria Division of the National Vector Borne
Disease Control Programme (NVBDCP), India
Prof. Andy Stergachis, Professor of Epide-
miology and Global Health, Adjunct Professor
of Pharmacy and Health Services, Director of
the Global Medicines Program, University of
Washington, USA
Dr Brenda Waning, Coordinator of Market
Dynamics at UNITAID, Switzerland
Dr Hashim Yusufu, Deputy Director, National
Agency for Food and Drug Administration and
Control, Nigeria
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, Glaxo-
SmithKline 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 Pharma-
ceutical Physician
Prof. Munir Pirmohamed, Professor of Clinical
Pharmacology, University of Liverpool, UK
MMV North America Inc. Board
* Joined in 2013
50
7 | Behind the scenes
David Reddy
Chief Executive Officer (CEO)
Nada Araeipour
Business Development Officer
Adam Aspinall*
Director, Product Management
Liridon Bajrami
Intern, Legal
Mark Baker
Associate Director, Translational Medicine
Jaya Banerji
Director, Advocacy and Communications
Lidiya Bebrevska*
Associate Director, Translational Medicine
Soazig Bertrand
Accounting & Finance Officer
Raphaëlle Bessette
Intern, Access & Product Management
Grégory Bonnaud
Senior Finance Officer
Isabelle Borghini-Fuhrer
Director, Clinical Development
Emilie Burlot
Project Coordinator, Drug Discovery
Jeremy Burrows
Head of Discovery
Andrea Buscaglia
Deputy Chief Financial Officer
Charlotte Cadoux*
HR Officer
Brice Campo
Associate Director, Drug Discovery
Stéphanie Cherbuin
Intern, Research & Development
Marion Colombani
Senior Legal Officer
Diana Cotran
Executive Vice President, Operations
Maud Couturier
Science Coordinator
Gelavizh Daghigh
Receptionist
Youcef Dahmane*
IT Support Technician
Per Dalén
Medical Director
Helen Demarest
Project Manager, Translational Medicine
Xavier Ding
Research Scientist
Heidi Divecha
Personal Assistant to the CSO
Christina do Paço
External Relations Officer
Matthew Doherty
Manager, Donor and Stakeholder Relations
Cristina Donini
Associate Director, Translational Medicine
Stephan Duparc
Chief Medical Officer
Alejandro Estrada
Office Manager
Sylvie Fonteilles-Drabek
Executive Vice President, Head of Legal
Penny Grewal Daumerie
Director, Access & Product Management
Romain Guibert
Travel Coordinator
Roberto Hanania
Legal Officer
Joan Herbert
Director, Business Development
Pierre Hugo
Associate Director,
Access & Product Management
George Jagoe
Executive Vice President,
Access & Product Management
Sarah Jeanneret
Project Coordinator, Drug Discovery
Franziska Karyabwite
HR Manager
Wiweka Kaszubska
Vice President, Head of Product Development
Sophie Kilisky
Intern, HR
Didier Leroy
Director, Drug Discovery
Julie Lotharius
Associate Director, Translational Medicine
Andrea Lucard
Executive Vice President, External Relations
Maud Lugand
Project Officer,
Access & Product Management
Adrienne MacDonald
Web Editor
Fiona Macintyre
Director, Translational Medicine
Aleksandra Misiorowska*
Associate Director,
Access & Product Management
Jörg Möhrle
Head of Translational Medicine
Claude Oeuvray
Director, Portfolio Management
Nouhoum Ouologuem*
TDR Fellow
Sophie Pereira
Finance Assistant
Alicja Poczatenko
Legal Officer
Elizabeth Poll
Editor and Publications Officer
Peter Potter-Lesage
Chief Financial Officer
Anya Ramalho
Director, Business Development
Elena Ramos
HR Coordinator
Marie-Ange Roustan
Finance Assistant
Thomas Rückle
Associate Director, Translational Medicine
Binetou Sané
Assistant, External Relations
Ndiogou Seck
Intern, Communications
Maria Sliwowska*
Quality Manager
Thomas Spangenberg
Research Scientist
Tareq Sunderji
Business Development/Legal Assistant
Yuko Takase
Finance Officer
David Ubben
Director, Clinical Development
Simona Valigova
Intern, Legal
Isabelle Vandenbroucke
Intern, Access & Product Management
David Waterson
Director, Drug Discovery
Helen Weir
Personal Assistant to the CEO
Tim Wells
Chief Scientific Officer (CSO)
Paul Willis
Associate Director, Drug Discovery
Bintou Zerbo
Intern, Legal
* Joined in 2013
DefeatingMalariaTogether
MMV team | Geneva, January 2013
MMV is grateful for the support in 2012 from the following institutional donors:
MMV is also grateful for the support received from private individuals
MCJ Amelior
Foundation
National Institutes of Health
(NIH/NIAID)
International Centre Cointrin
Route de Pré-Bois 20 PO Box 1826
1215 Geneva 15 Switzerland
Tel. +41 22 799 4060
Fax +41 22 799 4061
www.mmv.org
Editors Elizabeth Poll & Jaya Banerji, MMV
Designer ComStone - Pierre Chassany, Geneva, Switzerland
Printer Hertig + Cie SA, Lyss, Switzerland
Lithograph Catherine Vogt, Carouge, Switzerland
Photographs Anna Wang (p. 6), Antonio Mendes* (p. 12), Antonio Pinto* (p. 33), Ben Moldenhauer (cover), BMC St Jude
(p. 9), David Greyo* (p. 7), Elizabeth Poll (p. 22), Griffith University, Australia (p. 24a), Imperial College London, UK
(p. 13a), Indian mothers* (p. 44), Jayakumar from Shutterstock.com (p. 4), Jenn Warren* (pp. 24b & 46), Laura
Dem* (p. 19b), Lena Lorenz* (p. 52), London School of Hygiene & Tropical Medicine, UK (p. 23), Maud Lugand
(p. 8b), Medical Research Council Unit, Gambia (p. 19a), MMV (pp. 5, 16, 27b, 31b & 48), Morakinyo Afolabi*
(p. 14), Murtala Mohammed Specialist Hospital, Nigeria (p. 21), Natalia Szczygielska* (p. 2), National Institute
of Allergy and Infectious Diseases, USA (p. 30), Nicolas Spuhler (p. 51), Nijmegen Institute, the Netherlands
(p. 25a), Novartis (p. 19c), Novartis Foundation (p. 25b), Open Source Drug Discovery India (p. 28), Pierre Hugo
(p. 20), Roll Back Malaria Partnership (p. 10), Sandipan Majumdar* (p. 45), Sarah Hoibak* (p. 11), Sayla Velazquez*
(p. 27a), Séverine Pillet* (p. 8a), S. March-Riera & S. Bhatia, Massachusetts Institute of Technology, USA (p. 26),
University of Cape Town, South Africa (p. 31a) and University of Health & Allied Sciences, Ghana (p. 13b).
* Photograph from Swiss Malaria Group photo contest 2013 ‘Malaria: The BIG Picture’
AN
NU
AL R
EP
OR
T
2012