ANNUAL

REPORT

2012

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© 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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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

info@mmv.org

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

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2012