DNDi RA financ v14
14
DNDi Annual Report 2006 8 R&D Model, Strategy, & Portfolio DNDi ACTS AS A VIRTUAL ORGANISATION WHICH MANAGES COLLABORATIVE R&D PROJECTS. UTILISING A STEPWISE, INTEGRATED MODEL OF DRUG R&D, DNDi PRIMARILY FOCUSES ITS R&D EFFORTS ON TRYPANOSOMIASIS AND LEISHMANIASIS, WITH NEEDS- DRIVEN PROJECTS THAT CAN BE SOURCED AT ANY STAGE OF THE R&D PIPELINE. 02. R&D Model, Strategy, & Portfolio
Transcript of DNDi RA financ v14
DN
Di A
nnua
l Rep
ort 2
006
8
R&
D M
odel
, Str
ateg
y, &
Por
tfolio
DNDi ACTS AS A VIRTUAL
ORGANISATION WHICH
MANAGES COLLABORATIVE
R&D PROJECTS. UTILISING A
STEPWISE, INTEGRATED MODEL
OF DRUG R&D, DNDi PRIMARILY
FOCUSES ITS R&D EFFORTS
ON TRYPANOSOMIASIS AND
LEISHMANIASIS, WITH NEEDS-
DRIVEN PROJECTS THAT CAN BE
SOURCED AT ANY STAGE OF THE
R&D PIPELINE.
02.R&D Model, Strategy, & Portfolio
DNDi_RA_v23.indd 8 28/09/07 20:24:23
DNDi Annual Report 2006
9
R&D Model, Strategy, & Portfolio
DN
Di
foll
ow
s t
he
vir
tua
l re
se
arc
h m
od
el,
wh
ere
by
mo
st
res
ea
rch
is
ou
tso
urc
ed
an
d a
cti
vely
ma
na
ge
d b
y D
ND
i p
ers
on
ne
l e
xp
eri
en
ced
in
dif
fere
nt
as
pe
cts
of
ph
arm
ace
u-
tica
l d
eve
lop
me
nt.
DN
Di
pro
ac
tive
ly i
de
nti
fi e
s r
es
ea
rch
op
po
rtu
nit
ies
wit
h t
he
hig
he
st
po
ten
tia
l to
tra
ns
late
in
to i
mp
rove
d t
rea
tme
nt
op
tio
ns
, in
-so
urc
es
th
e p
roje
ct,
bu
ild
s t
he
full
de
velo
pm
en
t p
lan
, id
en
tifi
es
an
d c
on
tra
cts
th
e a
pp
rop
ria
te p
art
ne
rs f
or
ea
ch
ste
p, a
nd
ma
na
ge
s t
he
pro
jec
t a
s i
t p
rog
res
se
s t
hro
ug
h t
he
pip
eli
ne
.
Inclu
din
g p
ub
lic a
nd
aca
de
mic
re
se
arc
h i
nsti
tuti
on
s;
go
vern
me
nts
an
d d
ise
as
e c
on
tro
l
pro
gra
mm
es o
f n
eg
lecte
d d
isease-e
nd
em
ic c
ou
ntr
ies; i
nd
ivid
ual p
harm
ace
uti
cal a
nd
bio
tech
-
no
log
y co
mp
an
ies; N
GO
s, f
ou
nd
ati
on
s a
nd
oth
er
inst
itu
tio
ns in
volv
ed
in R
&D
an
d/o
r a
dvo
cacy
for
ne
gle
cte
d d
ise
ase
s; a
nd
ind
ivid
ua
l exp
ert
s -
DN
Di’s
co
lla
bo
rato
rs in
bo
th d
eve
lop
ed
an
d
de
velo
pin
g c
ou
ntr
ies a
re e
sse
nti
al.
Tog
eth
er
wit
h t
he
se
se
lecte
d p
art
ne
rs,
DN
Di
wil
l a
lso
en
su
re e
ffe
cti
ve p
ost-
reg
istr
ati
on
man
ag
em
en
t of t
hese
new
tre
atm
en
ts. M
ech
an
ism
s m
ust
be p
ut in
to p
lace
to e
nsu
re tre
atm
en
t,
uti
lisa
tio
n, a
nd
acc
ess
th
rou
gh
pa
rtn
ers
hip
wit
h in
tern
ati
on
al a
nd
na
tio
na
l p
rog
ram
me
s a
nd
to e
nsu
re t
ime
ly h
an
d-o
ver
of
pro
jects
to
co
mm
erc
ial
pa
rtn
ers
.
Th
e o
bje
cti
ve
is t
o b
uil
d
a r
ob
us
t,
we
ll-b
ala
nce
d
pip
eli
ne
fo
r
HA
T,
VL
, a
nd
Ch
ag
as
.
Ma
na
gin
g C
oll
ab
ora
tive
R
&D
Pro
jec
ts t
o B
rid
ge
Ga
ps
As
DN
Di
com
bin
es
ne
w d
rug
dis
cov-
ery
wit
h o
pti
mis
ati
on
of
exis
tin
g d
rug
s
an
d c
om
po
un
ds
, D
ND
i’s p
ort
foli
o w
ill
be
a m
ix o
f p
roje
cts
in-s
ou
rce
d a
t a
ny
sta
ge
of th
e d
eve
lop
me
nt
pro
cess
, fro
m
ea
rly d
isco
very
th
rou
gh
cli
nic
al
de
-
velo
pm
en
t. F
ive p
roje
ct c
ate
gori
es
can
be
dis
tin
gu
ish
ed
by
the
na
ture
of
the
com
po
un
d/t
reatm
en
t u
nd
er
con
sid
er-
ati
on
an
d b
y th
e s
tag
e o
f d
eve
lop
me
nt
or
exp
ecte
d t
ime
to
re
ach
pa
tie
nts
:
• N
ew
dru
gs f
rom
no
vel
co
mp
ou
nd
s
iden
tifi
ed
th
rou
gh
scr
een
ing
an
d le
ad
op
tim
isa
tio
n;
• N
ew
dru
gs
fro
m c
om
po
un
ds
wit
h
kn
ow
n a
nti
mic
rob
ial/
an
tip
ara
sit
ic
act
ivit
ies
(may
start
at
lead
op
tim
isa-
tio
n o
r p
re-c
lin
ica
l d
eve
lop
me
nt)
;
• N
ew
indic
ation
s fo
r ex
istin
g m
edic
ines
in t
he fi
eld
of th
e m
ost
neg
lect
ed
dis
-
ease
s (t
hera
peu
tic
swit
chin
g);
• R
efo
rmu
lati
on
s a
nd
co
mb
ina
tio
ns
be
tte
r a
da
pte
d t
o f
ield
co
nd
itio
ns
(paed
iatr
ic, l
on
g-a
ctin
g, n
ew
rou
te o
f
ad
min
istr
ati
on
, fi
xed
-dose
com
bin
a-
tio
ns, co
-pa
ck
ag
ing
, o
r co
-ad
min
is-
trati
on
);
• E
xisti
ng
dru
gs f
or
targ
et
dis
ea
se
s
(ge
og
rap
hic
al
ext
en
sio
n o
f re
gis
tra
-
tio
n;
co
mp
leti
on
of
reg
ula
tory
do
s-
sie
rs o
f exi
sti
ng
dru
g c
an
did
ate
s);
Th
e D
ND
i R
&D
te
am
wil
l p
roa
cti
vely
rea
ch
ou
t a
nd
bu
ild
a n
um
be
r o
f ex-
plo
rato
ry a
cti
viti
es w
hic
h,
de
pe
nd
ing
on
ou
tco
me
s,
ca
n b
e b
uil
t-u
p t
o f
ull
dru
g d
eve
lop
me
nt
pro
jects
or
ma
in-
tain
ed
as
ba
ck
up
pip
eli
ne
pro
jec
ts.
Th
rou
gh
th
is a
pp
roach
DN
Di w
ill m
ain
-
tain
a “
fee
de
r” s
yste
m f
or
the
pip
e-
lin
es o
f e
ach
ta
rge
t d
ise
ase
. S
ucc
ess
-
ful in
itia
l lin
ks
wit
h t
he p
harm
a/b
iote
ch
sect
or
will
be u
sed
to b
uild
fu
rth
er
con
-
tact
s an
d p
art
ners
hip
s, a
s w
ell
as
pro
-
vid
e s
om
e c
lea
r in
dic
ato
rs o
f e
ng
ag
e-
me
nt
wit
h in
du
str
y.
ST
RA
TE
GY
02
. R
&D
Mo
de
l, S
tra
teg
y,
& P
or
tfo
lio
PR
IOR
ITIE
S IN
200
6
> T
o c
ont
inue
to
bui
ld a
ro
bus
t p
ort
folio
for H
AT, l
eish
man
iasi
s, a
nd C
haga
s
> T
o d
evel
op
pro
ject
s fro
m le
ad s
elec
tion
to le
ad o
ptim
isat
ion,
with
pro
gres
sion
of
one
can
dida
te in
to le
ad o
ptim
izat
ion
> T
o c
ond
uct
fi ve
clin
ical
tri
als
and
to s
ubm
it re
gist
ratio
n fi l
es fo
r tw
o Fi
xed-
Dos
e A
rtes
unat
e-B
ased
Com
bina
tion
Ther
apie
s fo
r mal
aria
DN
Di_
RA
_v23
.indd
9
28/0
9/07
20
:24:
44
DNDi Annual Report 2006
10
R&D Model, Strategy, & Portfolio
In 2
00
6,
DN
Di’s
po
rtfo
lio
ha
s g
row
n
to 2
2 p
roje
cts
fro
m a
n i
nit
ial
thre
e i
n
20
03
. Th
e c
urr
en
t port
folio
ran
ges
from
dis
cove
ry t
o P
hase
III c
lin
ical
tria
ls a
nd
focu
ses
on
th
ree k
ineto
pla
stid
dis
ease
s
(vis
cera
l leis
hm
an
iasi
s, C
hagas
dis
ease
,
an
d s
leepin
g s
ickn
ess
) with
tw
o p
roje
cts
on
mala
ria. O
f th
e 2
2 pro
ject
s, tw
elv
e a
re
in th
e d
isco
very
ph
ase
, fou
r in
pre
clin
ical,
an
d s
ix in
clin
ical d
evelo
pm
en
t.
BR
IDG
ING
TH
E G
AP
S
Th
e o
bje
ctiv
es
of D
ND
i’s p
ort
folio s
trat-
eg
y a
re t
o b
rid
ge
th
e g
ap
s s
ee
n in
th
e
dru
g d
eve
lop
men
t p
ipelin
e b
y b
rin
gin
g
tog
eth
er
all
cu
rren
t kn
ow
led
ge a
nd
ca-
paci
ties
on
a tre
atm
en
t in
a c
oord
inate
d
man
ner. F
rom
dis
cove
ry th
rou
gh
clin
ical
tria
ls, an
d o
n t
o im
ple
men
tati
on
, n
ew
,
fi e
ld-r
ele
van
t to
ols
wil
l b
e b
rou
gh
t to
pati
en
ts in
th
e s
hort
est
poss
ible
tim
e.
DN
Di im
ple
me
nts
its
ph
arm
ace
uti
cal
R&
D p
rog
ram
s i
n c
oll
ab
ora
tio
n w
ith
pu
blic
an
d p
riva
te p
art
ners
base
d u
pon
the p
riori
ty n
eeds
of t
he p
opu
lation
s. T
he
org
an
isa
tio
n is u
sin
g e
xisti
ng
scie
nce
an
d R
&D
cap
aci
ty in
diffe
ren
t co
un
trie
s
to d
eve
lop
ess
en
tial m
ed
icin
es
an
d e
n-
sure
th
at
they
are
su
itab
le f
or,
an
d a
c-
cess
ible
to, th
e m
illion
s o
f p
eop
le s
uf-
feri
ng
fro
m n
eg
lecte
d d
ise
ase
s,
oft
en
livi
ng
in p
ove
rty
an
d in
rem
ote
are
as.
DN
Di m
ain
tain
s a
po
rtfo
lio
of p
roje
cts
at
all
sta
ge
s o
f d
eve
lop
me
nt,
fro
m
scre
en
ing
to d
rug
reg
istr
ati
on
, an
d h
as
the p
roje
ct
ma
na
gem
en
t sk
ills
to
su
p-
po
rt a
ll a
sp
ects
of
the
ir a
dva
nce
me
nt
thro
ug
h t
he
pip
eli
ne
.
TAR
GE
T P
RO
DU
CT
PR
OFI
LE
As a
pre
req
uis
ite
to
bu
ild
ing
a p
ort
-
foli
o s
tra
teg
y, t
he
de
sir
ed
R&
D o
ut-
co
me
, o
r th
e t
arg
et
pro
du
ct
pro
file
(TP
P),
ha
s t
o b
e d
efi
ne
d.
Ea
ch
R&
D
pro
ject
in t
he
po
rtfo
lio
wil
l b
e s
ele
ct-
ed
, pro
gre
sse
d, a
nd
ma
na
ge
d a
cco
rd-
ing
to
we
ll-d
efi
ne
d d
ecis
ion
ma
tric
es
ba
se
d o
n t
he
se
TP
Ps.
Pa
rtic
ula
rly
du
rin
g d
rug
dis
co
very
,
the
Ta
rge
t P
rod
uct
Pro
fi le
(T
PP
) ke
ep
s
rese
arc
h f
ocu
se
d o
n t
he
en
dg
am
e –
a m
ed
icin
e f
or
a p
ati
en
t. A
co
mm
on
form
at fo
r th
e T
PP
is a
‘pack
ag
e in
se
rt’
wh
ich
co
nta
ins a
ll o
f th
e i
nfo
rma
tio
n
ne
ce
ssa
ry f
or
a m
ed
ica
l p
racti
tio
ne
r
to e
ffe
cti
vely
pre
scri
be
th
e d
rug
. A
t
DN
Di,
ad
dit
ion
al
fea
ture
s i
nc
lud
e
a l
ow
ma
nu
fac
turi
ng
co
st,
to
ma
ke
the
dru
g m
ore
aff
ord
ab
le t
o p
ati
en
ts
an
d g
ove
rnm
en
ts,
an
d a
ro
bu
stn
ess
su
ite
d t
o t
he
ext
rem
es o
f cli
ma
te t
ha
t
ou
r d
rug
s w
ill
en
co
un
ter.
Th
e T
PP
pro
vid
es
a s
tate
me
nt
of
inte
nt
very
ea
rly
on
in
th
e d
rug
’s d
eve
lop
me
nt
pro
gra
m.
It s
tart
s a
s a
de
scri
pti
on
of
an
‘id
ea
l’ d
rug
, a
nd
ch
an
ge
s o
ver
the
deve
lop
me
nt
pro
cess
as lim
ita
tio
ns in
the
po
ten
tia
l d
rug
em
erg
e.
So
un
d k
no
wle
dg
e o
f p
ati
en
t n
ee
ds
is e
ss
en
tia
l to
a c
red
ible
TP
P.
It i
s
ne
ce
ssa
ry t
o s
oli
cit
inp
ut
fro
m h
ea
lth
ca
re w
ork
ers
, p
ati
en
ts,
he
alt
h r
eg
u-
lato
rs a
nd
po
licym
ak
ers
in
dis
ea
se
-
en
de
mic
co
un
trie
s t
ha
t a
re t
he
fi n
al
de
sti
na
tio
n f
or
the
dru
g.
Th
eir
in
clu
-
sio
n i
n t
he
ea
rly
sta
ge
s o
f th
e d
eci-
sio
n-m
ak
ing
pro
ce
ss
en
su
res
th
at
the
ir n
ee
ds i
n t
he
fi e
ld a
re r
efl
ecte
d
in t
he fi
na
l p
rod
uct.
Used
pro
perl
y, t
he
TP
P c
an
pla
y a
ce
ntr
al
role
in
th
e e
n-
tire
dru
g d
isco
very
an
d d
eve
lop
me
nt
pro
ce
ss.
Th
is r
ole
in
clu
de
s e
ffe
cti
ve
op
tim
isa
tio
n o
f d
rug
ca
nd
ida
tes, d
eci-
sio
n-m
ak
ing
wit
hin
an
org
an
isa
tio
n,
de
sig
n o
f cli
nic
al re
se
arc
h s
tra
teg
ies,
an
d c
on
str
ucti
ve c
om
mu
nic
ati
on
wit
h
reg
ula
tory
au
tho
riti
es.
BU
ILD
ING
A R
OB
US
T P
OR
TF
OL
IO
Dis
cove
ryP
recl
inic
alCl
inic
alA
vail
able
to p
atie
nts
Am
ph
ote
ric
in B
po
lym
er
(VL
)
TR
in
hib
ito
rs (
Le
ish
& T
ryp
s)
Mic
rotu
bu
le i
nh
ibit
ors
(H
AT
)
No
vel
nit
roh
ete
roc
ycle
s (
HA
T)
As
cofu
ran
on
e (
HA
T)
Sc
yne
xis
sc
ree
nin
g (
HA
T)
CD
RI
sc
ree
nin
g (
HA
T)
Dru
g c
om
bin
ati
on
s (
VL
)
Ge
nzy
me
sc
ree
nin
g
Be
nzo
furo
xa
ns
(C
ha
ga
s)
Pro
tein
fa
me
syl
tra
ns
fera
se
inh
ibit
ors
(H
AT
)
Pro
tea
se
in
hib
ito
rs K
77
7
(Ch
ag
as
)
Ex
plo
rato
ry s
cre
en
ing
, co
mp
ou
nd
‘m
inin
g’,
‘sw
itc
hin
g’
Kit
as
ato
sc
ree
nin
g (
HA
T)
Nit
roim
ida
zole
s 2
(H
AT
)
Nif
urt
imo
x-E
flo
mit
hin
e (
HA
T)
Nit
roim
ida
zole
s 1
(T
ryp
s)
CP
in
hib
ito
rs (
HA
T)
DH
FR
in
hib
ito
rs (
Le
ish
, T
ryp
s)
NP
C1
16
1B
,
an
8-a
min
oq
uin
oli
ne
(V
L)
Ra
vuco
na
zole
(C
ha
ga
s)
Art
es
un
ate
-Am
od
iaq
uin
e
com
bin
ati
on
(M
ala
ria
)
Art
es
un
ate
-Me
flo
qu
ine
com
bin
ati
on
(M
ala
ria
)
Pa
rom
om
ycin
(VL
in
Ea
st
Afr
ica
)
Imiq
uim
od
(CL
in
So
uth
Am
eri
ca
)
Am
Bis
om
e (
Le
ish
in
Afr
ica
)
HAT
: H
uman
Afr
ican
tr
ypan
osom
iasi
sVL
: Vi
scer
al le
ishm
ania
sis
CL:
C
utan
eous
le
ishm
ania
sis
Leis
h:
Leis
hman
iasi
sTr
yps:
Tr
ypan
osom
iasi
sC
haga
s: S
outh
Am
eric
an
tryp
anos
omia
sis
Ong
oing
Dis
cont
inue
d in
200
6
DN
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DNDi Annual Report 2006
11 R&D Model, Strategy, & Portfolio
A P
RA
GM
AT
IC IP
PO
LIC
Y
Co
ntr
act
term
s w
ith
pri
vate
an
d p
ub
lic
pa
rtn
ers
are
gu
ide
d b
y D
ND
i’s m
issio
n
to d
eve
lop
sa
fe, e
ffe
cti
ve, a
nd
aff
ord
ab
le
new
tre
atm
en
ts f
or
pa
tie
nts
su
ffe
rin
g
fro
m n
eg
lecte
d d
ise
ase
s, a
nd
to
en
su
re
eq
uit
ab
le t
rea
tme
nt
acc
ess
. C
on
tra
cts
are
en
tere
d in
to w
ith
th
ese
pri
ncip
les in
min
d a
nd
acc
ord
ing
to
its
IP
po
licy,
wh
ich
is “
gu
ide
d”
by
the
fo
llo
win
g p
rin
cip
les a
s
laid
do
wn
in
th
e b
usin
ess
pla
n:
• T
he
ne
ed
to
en
su
re t
ha
t d
rug
s a
re
aff
ord
ab
le a
nd
acce
ss is e
qu
ita
ble
for
pa
tie
nts
wh
o n
ee
d t
he
m;
• T
he
de
sir
e t
o d
eve
lop
dru
gs a
s p
ub
lic
go
od
s w
he
n p
oss
ible
.
Th
e D
ND
i IP
ap
pro
ach
is p
rag
ma
tic,
an
d d
ecis
ion
s r
eg
ard
ing
th
e p
oss
ible
acq
uis
itio
n o
f p
ate
nts
, o
wn
ers
hip
, a
nd
lice
nsin
g t
erm
s is m
ad
e o
n a
ca
se
-
by-
ca
se
ba
sis
. D
ND
i p
uts
th
e n
ee
ds o
f
ne
gle
cte
d p
ati
en
ts fi
rst,
an
d n
eg
oti
ate
s
to o
bta
in t
he
be
st
po
ssib
le c
on
dit
ion
s
for
the
m.
DN
Di’s
de
cis
ion
s r
eg
ard
ing
IP w
ill
co
ntr
ibu
te t
o e
nsu
rin
g a
cce
ss
an
d e
nco
ura
gin
g f
urt
he
r in
no
vati
on
.
DN
Di re
ga
rds d
rug
re
se
arc
h a
s a
pu
bli
c
go
od
th
at
sh
ou
ld p
rim
ari
ly l
ea
d t
o t
he
ad
van
ce
me
nt
of
he
alt
h.
In a
dd
itio
n t
o a
pra
gm
ati
c d
ay-
to-d
ay
ap
pro
ach
on
IP
,
DN
Di is
co
mm
itte
d t
o c
on
trib
uti
ng
to
the
de
velo
pm
en
t o
f IP
ap
pro
ach
es
in h
ea
lth
R&
D t
ha
t a
re a
ime
d a
t se
rvin
g
the
pu
bli
c g
oo
d.
02
. R
&D
Mo
de
l, S
tra
teg
y,
& P
or
tfo
lio
DN
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57
Ra
dic
al
imp
rov
em
en
t o
f th
era
pie
s f
or
the
leis
hm
an
ias
es
an
d t
he
try
pa
no
so
mia
se
s
req
uir
es
th
e i
de
nti
fi c
ati
on
, e
va
lua
tio
n,
an
d
de
ve
lop
me
nt
of
no
ve
l c
om
po
un
ds
th
at
are
sig
nifi
ca
ntl
y b
ett
er
tha
n c
urr
en
t th
era
pie
s.
Th
e g
row
th i
n D
ND
i’s p
roje
ct
nu
mb
er
to 2
2
in 2
00
6 f
rom
fo
ur
in 2
00
3 h
as b
ee
n l
arg
ely
in
dis
cove
ry (w
ith
twelv
e p
roje
cts
at t
he e
nd o
f 2006).
Th
e la
rge n
um
ber
of p
roje
cts
in d
isco
very
is d
ue
to t
he n
eed
to ‘f
eed
’ th
ree d
iffe
ren
t d
isease
pro
-
gra
mm
es
an
d to
com
pen
sate
for
the h
igh
att
rition
rate
of
the d
rug
deve
lop
men
t p
ipelin
e.
Mass
ive, c
on
cert
ed
eff
ort
s fo
cuse
d o
n d
isco
very
mu
st
an
d a
re b
ein
g u
nd
ert
ak
en
in
ord
er
to
ach
ieve
a r
ob
ust
R&
D p
ipe
lin
e.
In o
rde
r to
ma
xim
ize
re
so
urc
es, c
om
po
un
ds in
dis
co
very
pro
jects
are
in
itia
lly
teste
d a
ga
inst
all
kin
eto
pla
sti
ds.
Ba
se
d o
n t
he
da
ta a
t th
is
stag
e, D
ND
i th
en
makes a
decis
ion
on
wh
eth
er
to f
ocu
s t
he
pro
ject
on
a s
pe
cifi
c d
ise
ase
in
furt
he
r d
eve
lop
me
nt.
Dis
co
very
in
clu
de
s:
• S
cre
en
ing
of
com
po
un
ds a
ga
inst
th
e p
ath
o-
ge
ns t
ha
t ca
use
th
e t
arg
et
dis
ea
se
;
• H
it e
xpan
sion
, w
here
ch
em
ical m
odifi c
ation
is
ap
plied
on
th
e h
its f
or
imp
rove
d e
ffic
acy
an
d
sele
ctiv
ity;
• L
ea
d i
de
nti
fi ca
tio
n,
wh
ere
fu
rth
er
in v
itro
,
in v
ivo
, a
nd
ad
min
istr
ati
on
, d
istr
ibu
tio
n,
me
tab
oli
sm
, a
nd
ext
racti
on
(A
DM
E)
stu
d-
ies id
en
tify
a s
ma
ll s
eri
es o
f co
mp
ou
nd
s fo
r
lea
d o
pti
mis
ati
on
.
���T
RY
PA
NO
TH
ION
E
RE
DU
CT
AS
E I
NH
IBIT
OR
S
• T
arg
et
dis
ea
se
:tr
ypan
osom
iasi
s an
d le
ishm
ania
sis
• P
art
ne
r: U
nive
rsity
of D
unde
e, U
K.
• D
ND
i P
roje
ct
Ma
na
ge
r: D
enis
Mar
tin
• P
roje
ct
sta
rt:
June
200
4
The
enzy
me
tryp
anot
hion
e re
duct
ase
(TR
) is
a va
lidat
ed d
rug
targ
et fo
r tr
ypan
osom
ia a
nd le
ishm
ania
par
asite
s.
With
that
in m
ind,
the
proj
ect o
bjec
tive
is to
iden
tify
new
che
mot
ypes
, via
th
e au
tom
ated
scr
eeni
ng o
f lar
ge
com
poun
d lib
rarie
s an
d pe
rform
ing
ratio
nal d
esig
n an
d ch
emis
try
on
poss
ible
hits
, whi
ch p
oten
tly a
nd
sele
ctiv
ely
inhi
bit t
rypa
noth
ione
re
duct
ase.
A
t the
end
of 2
006,
the
med
ium
-th
roug
hput
scr
eeni
ng, p
erfo
rmed
at
Dun
dee,
has
iden
tifi e
d a
num
ber
of
inte
rest
ing
‘hits
’ am
ong
tric
yclic
s an
d a
num
ber
of o
ther
che
mic
al s
truc
ture
s fro
m li
brar
ies
prov
ided
by
Sig
ma
and
Gla
xoS
mith
Klin
e. F
urth
er s
cree
ning
-
incl
udin
g m
olec
ular
targ
et-b
ased
, w
hole
cel
l, an
d ro
dent
- a
nd a
dditi
onal
ch
emis
try
of c
ompo
unds
rela
ted
to th
e cu
rren
t tric
yclic
lead
s an
d hi
ts w
ill be
pe
rform
ed.
��� D
IHY
DR
OF
OL
AT
E
RE
DU
CT
AS
E I
NH
IBIT
OR
S
• T
arg
et
dis
ea
se
s:
tryp
anos
omia
sis
and
leis
hman
iasi
s
• P
art
ne
rs:
Inst
itute
of P
aras
itolo
gy a
nd
Bio
med
icin
e Lo
pez-
Ney
ra, S
pain
; B
IOTE
C, T
haila
nd; B
asile
a, S
witz
erla
nd;
Sw
iss
Trop
ical
Inst
itute
, Sw
itzer
land
.
• D
ND
i P
roje
ct
Ma
na
ge
r: D
enis
Mar
tin
• P
roje
ct
sta
rt:
Aug
ust 2
005
Enz
ymes
invo
lved
in fo
late
met
abol
ism
, es
peci
ally
dih
ydro
fola
te re
duct
ase
(DH
FR),
have
bee
n su
cces
sful
ly
targ
eted
for
canc
er a
nd a
ntim
icro
bial
in
fect
ions
by
limiti
ng th
e en
ergy
sup
ply
to th
e in
fect
ious
cel
l. M
ost D
HFR
in
hibi
tors
are
not
sui
tabl
e ca
ndid
ates
fo
r pa
rasi
tic d
isea
ses
beca
use
they
ar
e m
ore
sele
ctiv
e to
war
ds th
e hu
man
Dis
cove
ry P
roje
cts
A L
OO
K A
T T
HE
DN
Di
PO
RT
FO
LIO
BY
ST
AG
E A
ND
BY
PR
OJ
EC
T
DNDi Annual Report 2006
12
R&D Model, Strategy, & Portfolio
DN
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20
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07
enzy
me
than
tow
ards
the
para
site
en
zym
e. T
here
may
als
o be
a s
econ
d en
zym
e, w
hich
mus
t als
o be
inhi
bite
d in
or
der
for
DH
FR in
hibi
tors
to s
ucce
ssfu
lly
kill
the
para
site
. The
obj
ectiv
e of
the
proj
ect i
s to
iden
tify,
via
in v
itro
and
in
vivo
scr
eens
, par
asite
-spe
cifi c
DH
FR
inhi
bito
rs th
at k
ill th
e pa
rasi
te.
At t
he e
nd o
f 200
6, c
ompo
unds
from
B
asile
a ha
ve b
een
scre
ened
aga
inst
the
enzy
me
at th
e In
stitu
te o
f Par
asito
logy
an
d B
iom
edic
ine
Lope
z N
eyra
; hits
hav
e al
so b
een
iden
tifi e
d fo
r in
vitr
o pa
rasi
te
scre
enin
g at
STI
. For
200
7, S
TI w
ill st
udy
the
com
poun
ds’ i
n vi
vo e
ffi ca
cies
in
a m
ouse
mod
el s
o th
at a
sho
rt li
st o
f ca
ndid
ates
for
lead
exp
ansi
on w
ill be
re
ady
by th
e en
d of
the
year
.
��� M
ICR
OT
UB
UL
E I
NH
IBIT
OR
S
• T
arg
et
dis
ea
se
:hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
rs:
Mur
doch
Uni
vers
ity, A
ustr
alia
(Prin
cipa
l In
vest
igat
or a
nd in
vitr
o T.
bru
cei
assa
ys);
Sw
iss
Trop
ical
Inst
itute
, S
witz
erla
nd (i
n vi
vo m
odel
s); E
pich
em,
Aus
tral
ia (m
edic
inal
che
mis
try)
; Cen
tre
for
Dru
g C
andi
date
Opt
imiz
atio
n,
Mon
ash
Uni
vers
ity, A
ustr
alia
(p
harm
acok
inet
ics,
AD
ME
, and
to
xico
logy
).
• D
ND
i P
roje
ct
Ma
na
ge
r: R
ober
t Don
• P
roje
ct
sta
rt:
Sep
tem
ber
2006
Pre
viou
s st
udie
s ha
ve s
how
n th
at n
ovel
co
mpo
unds
whi
ch b
ind
to tr
ypan
osom
e al
pha-
tubu
lin h
ave
sele
ctiv
e ac
tivity
to
T. b
ruce
i alp
ha-t
ubul
in v
ersu
s m
urin
e al
pha-
tubu
lin. T
he p
urpo
se o
f thi
s pr
ojec
t is
to a
sses
s th
e de
velo
pmen
t po
tent
ial o
f thi
s le
ad s
erie
s. A
t the
end
of
200
6, m
ore
than
50
com
poun
ds
have
bee
n sy
nthe
size
d an
d ar
e be
ing
asse
ssed
in v
itro
for
antip
aras
itic
activ
ity
and
pote
ntia
l mut
agen
icity
. In
2007
, th
is re
itera
tive
med
icin
al c
hem
istr
y an
d sc
reen
ing
wor
k w
ill be
con
tinue
d. If
pr
omis
ing
lead
s ar
e id
entifi
ed,
in v
ivo
toxi
colo
gy m
ay b
e un
dert
aken
.
��� C
YS
TE
INE
PR
OT
EA
SE
IN
HIB
ITO
RS
• T
arg
et
dis
ea
se
:tr
ypan
osom
iasi
s (H
AT a
nd C
haga
s)
• P
art
ne
r:
Uni
vers
ity o
f Cal
iforn
ia, S
an F
ranc
isco
, U
SA
.
• D
ND
i P
roje
ct
Ma
na
ge
r: D
enis
Mar
tin
• P
roje
ct
sta
rt:
Oct
ober
200
5
Cys
tein
e pr
otea
ses
(CP
), es
peci
ally
a
subg
roup
of t
he p
apai
n fa
mily
whi
ch
is n
early
ubi
quiti
ous
in p
roto
zoan
pa
rasi
tes,
hav
e be
en id
entifi
ed
as
prom
isin
g ta
rget
s fo
r th
e de
velo
pmen
t of
ant
ipar
asiti
c ch
emot
hera
py.
Thes
e pr
otea
ses
play
a n
umbe
r of
ke
y ro
les
in p
aras
ite s
urvi
val (
from
nu
triti
on to
imm
une
evas
ion
amon
g ot
hers
), an
d m
uch
is k
now
n ab
out
the
stru
ctur
e/fu
nctio
n re
latio
nshi
p of
the
enzy
me
fam
ily. A
num
ber
of
mam
mal
ian
hom
olog
ues
exis
t to
man
y of
the
para
sitic
enz
ymes
, whi
ch
mea
ns th
ere
has
been
a c
onsi
dera
ble
amou
nt o
f pha
rmac
eutic
al re
sear
ch
done
on
inhi
bito
rs o
f thi
s pr
otei
n fa
mily
. The
refo
re, t
his
enzy
me
fam
ily
has
grea
t pot
entia
l as
a ta
rget
for
disc
over
y re
sear
ch. T
he o
bjec
tive
is
to id
entif
y no
vel i
nhib
itors
of p
aras
ite
CP
s fro
m th
ree
clas
ses
(vin
yl s
ulfo
nes,
di
hydr
azid
es, a
nd th
iose
mic
arba
zone
s)
so a
s to
gen
erat
e le
ad c
ompo
unds
ca
pabl
e of
elim
inat
ing
the
para
sita
emia
in
ani
mal
dis
ease
mod
els
of H
AT.
���N
OV
EL
N
ITR
OH
ET
ER
OC
YC
LE
S
• T
arg
et
dis
ea
se
:hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
rs:
Uni
vers
ity o
f Dun
dee,
UK
(Prin
cipa
l in
vest
igat
or);
Gla
sgow
Uni
vers
ity, U
K;
Uni
vers
ity o
f Par
ma,
Ital
y; S
wis
s Tr
opic
al
Inst
itute
, Sw
itzer
land
.
• D
ND
i P
roje
ct
Ma
na
ge
r: E
ls T
orre
ele
• P
roje
ct
sta
rt:
June
200
5
The
obje
ctiv
e is
to id
entif
y le
ad
com
poun
ds fo
r H
AT fr
om a
new
ser
ies
of m
elam
ine-
nitr
ofur
an c
onju
gate
s.
Pro
of-o
f-pr
inci
plei
s to
det
erm
ine
if co
mpo
unds
with
goo
d an
titry
pano
som
e ac
tivity
(in
vivo
act
ivity
in a
cute
and
ch
roni
c m
ouse
mod
els
for
HAT
) and
w
ith a
n ac
cept
able
toxi
city
pro
fi le
can
be g
ener
ated
. One
com
mon
pro
blem
of
nitr
ohet
eroc
ycle
com
poun
ds, h
owev
er,
is g
enot
oxic
ity, w
hich
is li
kely
to b
e an
is
sue
for
the
hybr
id c
ompo
unds
as
wel
l. A
sec
ond
chal
leng
e is
to g
ener
ate
com
poun
ds th
at c
an c
ross
the
BB
B
and
can
cure
the
CN
S-s
tage
of t
he
dise
ase.
At t
he e
nd o
f 200
6, 5
0 ne
w
com
poun
ds h
ad b
een
gene
rate
d an
d th
eir
activ
ity/t
oxic
ity p
rofi l
e as
sess
ed.
���K
ITA
SA
TO
SC
RE
EN
ING
• T
arg
et
dis
ea
se
:hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
rs:
Kita
sato
Inst
itute
(KIT
), Ja
pan;
Sw
iss
Trop
ical
Inst
itute
(STI
), S
witz
erla
nd.
• D
ND
i P
roje
ct
Ma
na
ge
r: S
imon
Cro
ft
• P
roje
ct
sta
rt:
Apr
il 20
05
The
goal
of t
his
proj
ect i
s to
est
ablis
h sc
reen
s of
nat
ural
sub
stan
ces
as a
po
ssib
le s
ourc
e of
new
com
poun
ds
with
act
ivity
aga
inst
Try
pano
som
a br
ucei
, with
a re
sear
ch p
artn
er w
ho h
as
year
s of
exp
erie
nce
in n
atur
al p
rodu
cts’
sc
reen
ing
and
dem
onst
rate
d su
cces
s w
ith th
e id
entifi
cat
ion
of th
e w
idel
y us
ed a
ntib
iotic
, ive
rmec
tin. S
taff
from
an
othe
r pa
rtne
r, S
TI, w
ith e
xper
tise
in
kine
topl
astid
rese
arch
, wer
e tr
aine
d in
in
vitr
o an
d in
viv
o te
chni
ques
for
T. b
ruce
i
DNDi Annual Report 2006
13 R&D Model, Strategy, & Portfolio
02
. R
&D
Mo
de
l, S
tra
teg
y,
& P
or
tfo
lio
DN
Di_
RA
_v23
.indd
13
28/0
9/07
20
:25:
13
Dis
cove
ry P
roje
cts
DNDi Annual Report 2006
14
R&D Model, Strategy, & Portfolio
assa
ys, t
hen
tran
sfer
red
the
met
hods
to
KIT
. At t
he e
nd o
f 200
6, o
ver
12,0
00
natu
ral p
rodu
cts
and
thei
r sy
nthe
tic
deriv
ativ
es h
ave
been
scr
eene
d, w
ith
ten
com
poun
ds id
entifi
ed
as h
avin
g hi
gh a
ctiv
ity a
nd n
ot b
eing
kno
wn
anti-
canc
er c
ompo
unds
. In
2007
, fu
rthe
r w
ork
will
be c
arrie
d ou
t in
vivo
to
stud
y th
e ac
tivity
of t
he te
n pr
omis
ing
com
poun
ds, a
nd le
ads
will
also
be
test
ed a
gain
st T
. cru
zi a
nd L
. don
ovan
i.
��� C
OM
PO
UN
D S
CR
EE
NIN
G
WIT
H S
CY
NE
XIS
• T
arg
et
dis
ea
se
:hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
r: S
cyne
xis,
US
A
• D
ND
i P
roje
ct
Tea
m:
Rob
ert D
on, D
enis
Mar
tin
• P
roje
ct
sta
rt:
July
200
6
The
curr
ent o
bjec
tive
is to
est
ablis
h a
T. b
ruce
i in
vitro
scr
een
at S
cyne
xis,
to
scre
en th
e S
cyne
xis
libra
ry o
f 25,
000
com
poun
ds in
a w
hole
cel
l in
vitro
sc
reen
and
to s
elec
t com
poun
ds w
ith
sele
ctiv
ity fo
r a
full
lead
opt
imiz
atio
n pr
ogra
mm
e. A
t the
end
of 2
006,
an
actio
n pl
an a
nd a
gree
men
t are
in p
lace
, w
ith T
. bru
cei c
ultu
res
esta
blis
hed.
Va
lidat
ion
of th
e sc
reen
ing
proc
edur
es
is o
ngoi
ng. P
roje
ct-s
peci
fi c te
mpl
ates
fo
r th
e H
EO
S o
nlin
e da
taba
se h
ave
also
be
en d
esig
ned.
��� C
OM
PO
UN
D S
CR
EE
NIN
G
WIT
H G
EN
ZY
ME
• T
arg
et
dis
ea
se
:hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
r: G
enzy
me
• D
ND
i P
roje
ct
Tea
m:
Rob
ert D
on, D
enis
Mar
tin
• P
roje
ct
sta
rt:
July
200
6G
enzy
me
will
prov
ide
a nu
mbe
r of
com
poun
ds th
at im
pact
on
the
poly
amin
e bi
osyn
thes
is fo
r scr
eeni
ng a
gain
st
T. b
ruce
i at t
he S
wis
s Tr
opic
al In
stitu
te.
Thes
e ha
ve b
een
stud
ied
as p
art o
f the
ir on
colo
gy p
rogr
amm
e an
d th
is p
athw
ay
is a
lso
the
targ
et fo
r DFM
O (E
fl orn
ithin
e)
in T
. bru
cei.
A c
ontra
ct h
as b
een
sign
ed. A
ll co
mpo
unds
hav
e be
en s
uppl
ied
to
STI
and
scr
eene
d. T
wel
ve c
eram
ide
anal
ogue
s sh
ow >
75%
gro
wth
inhi
bitio
n of
T. b
ruce
i in v
itro
at 0
.8 μ
g/m
l.
��� C
OM
PO
UN
D S
CR
EE
NIN
G
WIT
H C
DR
I
• T
arg
et
dis
ea
se
:hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
r:
Cen
tral
Dru
g R
esea
rch
Inst
itute
(CD
RI)
• D
ND
i P
roje
ct
Ma
na
ge
r:
Sim
on C
roft
• P
roje
ct
sta
rt:
Febr
uary
200
6
The
goal
of t
his
proj
ect i
s to
iden
tify
som
e ch
emic
ally
div
erse
com
poun
ds w
ith in
vi
tro a
ctiv
ity a
gain
st T
. bru
cei.
CD
RI –
ba
sed
in L
uckn
ow, I
ndia
– is
per
form
ing
a hi
gh-t
horo
ughp
ut s
cree
ning
of a
libra
ry
of 1
6,00
0 co
mpo
unds
. In
2006
, an
actio
n pl
an w
as a
gree
d up
on; s
taff
train
ing,
te
chno
logy
tran
sfer
, and
ass
ay v
alid
atio
n w
ere
also
com
plet
ed. B
y th
e fo
urth
qu
arte
r of 2
006,
scr
eeni
ng h
ad b
egun
, w
ith th
e 20
07 p
lan
to c
ompl
ete
scre
enin
g ag
ains
t T. b
ruce
i an
d a
mam
mal
ian
cell
line.
Fur
ther
lead
iden
tifi c
atio
n is
pla
nned
fo
r tw
o or
thre
e ch
emic
al c
lass
es w
hich
sh
ow p
rom
isin
g ac
tivity
and
cyt
otox
icity
pr
ofi le
s.
���A
SC
OF
UR
AN
ON
E
• T
arg
et
dis
ea
se
:hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
rs:
Uni
vers
ity o
f Tok
yo
Sch
ool o
f Med
icin
e, J
apan
(Prin
cipa
l In
vest
igat
or);
Tott
ori U
nive
rsity
, Jap
an;
Nag
ayo
Uni
vers
ity, J
apan
.
• D
ND
i P
roje
ct
Ma
na
ge
r: S
imon
Cro
ft
• P
roje
ct
sta
rt:
Oct
ober
200
4
Sev
eral
yea
rs a
go, r
esea
rche
rs a
t the
U
nive
rsity
of T
okyo
Sch
ool o
f Med
icin
e id
entifi
ed
the
in v
itro
and
in v
ivo
activ
ity
of a
scof
uran
one
agai
nst T
rypa
noso
ma
bruc
ei, t
he p
aras
ite re
spon
sibl
e fo
r sl
eepi
ng s
ickn
ess.
In th
e ve
terin
ary
fi eld
, su
bseq
uent
pub
lishe
d re
sear
ch h
as
stud
ied
the
mec
hani
sm o
f act
ion
and
antit
rypa
noso
mal
act
ivity
in u
ngul
ates
lik
e co
ws
and
shee
p. H
owev
er, t
here
ar
e a
num
ber
of li
mita
tions
to th
is
activ
ity w
hich
mus
t be
furt
her
stud
ied.
S
ubm
itted
via
a le
tter
of i
nter
est a
nd
appr
oved
by
the
SA
C in
Oct
ober
20
04, t
he p
roje
ct o
bjec
tive
is to
iden
tify
asco
fura
none
der
ivat
ives
with
hig
h se
lect
ivity
for
the
HAT
par
asite
and
with
dr
ug-li
ke p
rope
rtie
s in
a le
ad re
fi nem
ent
proj
ect.
In 2
006,
neg
otia
tions
con
tinue
d w
ith th
e Ja
pane
se b
iote
ch c
ompa
ny
that
ow
ns th
e IP
on
the
mol
ecul
es s
o th
at th
e re
sear
ch p
artn
ers
can
cont
inue
th
eir
wor
k on
the
activ
ity p
rofi l
e an
d ch
emis
try
of th
is c
ompo
und
in 2
007.
PR
OJE
CT
S D
ISC
ON
TIN
UE
D
IN 2
006
DIS
CO
VE
RY:
Pro
tein
farn
esyl
tran
sfer
ase
inhi
bito
rs
(HAT
). P
artn
er: U
nive
rsity
of W
ashi
ngto
n, U
SA
.
Ben
zofu
roxa
ns (C
hag
as).
Par
tner
s: U
nive
rsid
ad d
e la
Rep
ublic
a,
Uru
guay
(Prin
cipa
l Inv
estig
ator
); U
nive
rsi-
dad
de N
avar
ra, S
pain
; IIB
CE
, Uru
guay
; U
nive
rsid
ad N
acio
nal d
e S
alta
, Arg
entin
a.
PR
EC
LIN
ICA
L:
Pro
teas
e in
hib
itor
K77
7 (C
hag
as).
Par
tner
s: F
eder
al U
nive
rsity
of M
inas
G
erai
s, B
razi
l; U
nive
rsity
of C
alifo
rnia
, U
SA
; Ein
stei
n S
choo
l of M
edic
ine,
US
A.
DN
Di i
s gr
atef
ul to
the
proj
ect p
artn
ers
for
thei
r ded
icat
ion
durin
g th
e liv
es o
f the
se
proj
ects
.
OHC
Ascofuranone
OH
OH
O
O
CI
H3C
DN
Di_
RA
_v23
.indd
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20
:25:
26
DNDi Annual Report 2006
15 R&D Model, Strategy, & Portfolio
Re
dis
cove
rin
g n
itro
imid
azo
les
as
pro
mis
ing
dru
g c
an
did
ate
s
� N
ITR
OIM
IDA
ZO
LE
S-1
• T
arg
et
dis
ea
se
:tr
ypan
osom
iasi
s (H
AT a
nd C
haga
s); l
eish
man
iasi
s
• P
art
ne
rs:
Sw
iss
Trop
ical
Inst
itute
, Sw
itzer
land
(com
poun
d ev
alua
tion)
; sev
eral
CR
O’s
incl
udin
g C
ovan
ce, U
K; B
ioD
ynam
ics,
U
K, A
bsor
ptio
n S
yste
ms,
US
; and
a r
ange
of c
olla
bora
tors
who
hav
e m
ade
com
poun
ds o
f int
eres
t ava
ilabl
e fo
r te
stin
g, in
clud
ing
ENH
Res
earc
h In
stitu
te, U
SA
; Teh
ran
Uni
v of
Med
ical
Sci
ence
s, Ir
an; S
ilesi
an U
niv
of T
echn
olog
y,
Pol
and;
LaS
apie
nza
Uni
v, It
aly;
Uni
v of
Alb
erta
, Can
ada;
Uni
v of
Ten
ness
ee, U
SA
; Tok
ushi
ma
Uni
v, J
apan
; Uni
v of
A
uckl
and,
Aus
tral
ia; s
anofi
-ave
ntis
, Fra
nce;
Roc
he, S
witz
erla
nd; N
ovar
tis/N
ITD
, US
A-C
H-S
inga
pore
; Alk
em, I
ndia
; TB
A
llianc
e, U
SA
.
• D
ND
i P
roje
ct
Ma
na
ge
r:
Els
Tor
reel
e
• P
roje
ct
sta
rt:
Janu
ary
2005
In 2
004,
DN
Di c
omm
issi
oned
a li
tera
ture
/pat
ent r
evie
w to
exp
lore
pas
t and
ong
oing
rese
arch
act
iviti
es o
n m
egaz
ol
and
rela
ted
nitr
oim
idia
zole
com
poun
ds a
s po
ssib
le le
ads
for
antit
rypa
noso
mal
dru
g de
velo
pmen
t bec
ause
they
ha
d pr
evio
usly
bee
n sh
own
to p
osse
ss g
ood
antim
icro
bial
act
ivity
, inc
ludi
ng a
nti-p
roto
zoal
act
ivity
. In
the
case
of
meg
azol
, whi
ch h
ad p
rove
n hi
ghly
act
ive
in v
itro
and
in v
ivo
as a
tryp
anoc
idal
com
poun
d an
d a
prom
isin
g po
tent
ial d
rug
cand
idat
e ag
ains
t Cha
gas
dise
ase
and
HAT
, it w
as o
rally
act
ive
and
coul
d cr
oss
the
bloo
d-br
ain
barr
ier.
How
ever
, due
to it
s to
xici
ty (s
peci
fi cal
ly m
utag
enic
ity, o
r po
ssib
ility
of c
ausi
ng g
enet
ic m
utat
ion)
, it w
as n
ot
deve
lope
d fu
rthe
r.
Afte
r es
tabl
ishi
ng th
e po
tent
ial o
f the
cla
ss, D
ND
i und
erto
ok a
pro
ject
to id
entif
y a
rang
e of
new
and
old
ni
troh
eter
ocyc
les,
to (r
e)as
sess
thei
r in
vitr
o an
d in
viv
o tr
ypan
ocid
al a
ctiv
ity, a
nd e
valu
ate
thei
r ac
tivity
/gen
otox
icity
pr
ofi le
thro
ugh
a se
ries
of s
tand
ard
geno
toxi
city
test
s. In
par
alle
l, ot
her
drug
abilit
y ch
arac
teris
tics
wer
e su
mm
arily
co
mpi
led
to a
llow
com
paris
on o
f the
mos
t pro
mis
ing
com
poun
ds. N
ear
the
end
of 2
006,
the
proj
ect w
as a
lso
expa
nded
to in
clud
e le
ishm
ania
sis
as a
targ
et, a
s se
vera
l com
poun
ds d
emon
stra
ted
good
in v
itro
activ
ity a
gain
st
L. d
onov
ani.
At t
he e
nd o
f 200
6, o
ver
500
com
poun
ds fr
om 1
5 di
ffere
nt s
ourc
es h
ave
been
iden
tifi e
d, a
cces
sed,
and
test
ed
at S
TI fo
r in
vitr
o an
tipar
asiti
c ac
tivity
, and
furt
her
asse
ssed
for
in v
ivo
sele
ctiv
ity. S
ever
al in
tere
stin
g co
mpo
und
serie
s ha
ve b
een
iden
tifi e
d an
d se
lect
ed fo
r fu
rthe
r ex
plor
atio
n. T
wo
com
poun
ds fr
om R
oche
and
san
ofi -
aven
tis
(ex-
Hoe
chst
) wer
e id
entifi
ed
as p
recl
inic
al c
andi
date
s (s
ee N
itroi
mid
azol
es-2
).
02
. R
&D
Mo
de
l, S
tra
teg
y,
& P
or
tfo
lio
DN
Di_
RA
_v23
.indd
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28/0
9/07
20
:25:
36
DNDi Annual Report 2006
16
R&D Model, Strategy, & Portfolio
A l
oo
k a
t th
e c
urr
en
t s
tatu
s o
f R
&D
re
se
arc
h
for
the
try
pa
no
so
mia
se
s a
nd
le
ish
ma
nia
se
s,
reve
als
a c
lea
r sh
ort
ag
e o
f p
roje
cts in
pre
clin
i-
cal
de
velo
pm
en
t, w
hic
h r
ais
es
co
nce
rn a
bo
ut
po
ten
tia
l ne
w d
rug
s in
fi ve
to
te
n y
ea
rs t
ime
. To
red
ress
th
e b
ala
nce
, DN
Di i
s ta
kin
g a
pro
acti
ve
ap
pro
ach
to
id
en
tify
ne
w d
rug
s a
nd
pro
jects
that h
ave
th
e p
oss
ibilit
y of fi
llin
g th
is p
recl
inic
al
ga
p. A
lre
ad
y, p
roje
cts
on
nit
roim
idia
zole
s a
nd
am
ino
qu
ino
lin
es h
ave
be
en
esta
bli
sh
ed
to
fi l
l
this
im
me
dia
te n
ee
d.
DN
Di
als
o r
eco
gn
ise
s
the
ne
ed
fo
r n
ew
dis
ea
se
-sp
ecifi
c m
od
els
to
imp
rove
th
e s
ele
cti
on
of
dru
gs in
th
e d
eve
lop
-
me
nt
ph
ase
s, a
nd
is w
ork
ing
wit
h p
art
ne
rs t
o
ide
nti
fy n
ew
po
ten
tia
l ca
nd
ida
tes.
Pre
clin
ical
Pro
ject
s
��N
ITR
OIM
IDA
ZO
LE
S –
2
• T
arg
et
dis
ea
se
: hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
rs:
Sw
iss
Trop
ical
Inst
itute
(STI
), S
witz
erla
nd (c
ompo
und
eval
uatio
n);
seve
ral C
RO
’s in
clud
ing
Cov
ance
UK
; B
ioD
ynam
ics,
UK
, Abs
orpt
ion
Sys
tem
s,
US
; san
ofi -
aven
tis, F
ranc
e; R
oche
, S
witz
erla
nd.
• D
ND
i P
roje
ct
Ma
na
ge
r: E
ls T
orre
ele
• P
roje
ct
sta
rt:
Dec
embe
r 20
06
In D
ecem
ber o
f 200
6, th
e tw
o m
ost
adva
nced
com
poun
ds (c
omin
g fro
m
Roc
he a
nd s
anofi
-ave
ntis
) of t
he
“Nitr
oim
idaz
oles
-1”
(re-)
disc
over
y pr
ojec
t w
ere
sepa
rate
d in
to th
eir o
wn
proj
ect.
This
sep
arat
ion
was
don
e in
or
der t
o fu
rthe
r cha
ract
eriz
e th
em a
nd
to s
elec
t the
mos
t pro
mis
ing
of th
e tw
o to
adv
ance
into
pre
clin
ical
dev
elop
men
t in
200
7. F
urth
er c
hara
cter
izat
ion
will
incl
ude
met
abol
ic p
rofi l
e, P
K,
and
mut
agen
ic p
oten
tial o
f the
two
cand
idat
es.
���N
PC
11
61
B,
AN
8-A
MIN
OQ
UIN
OL
INE
• T
arg
et
dis
ea
se
: vi
scer
al le
ishm
ania
sis
• P
art
ne
rs:
Uni
vers
ity o
f Mis
siss
ippi
(U
M),
US
A (P
rinci
pal I
nves
tigat
or);
Med
icin
es fo
r M
alar
ia V
entu
re (M
MV
),
Sw
itzer
land
; Lon
don
Sch
ool o
f Hyg
iene
&
Tro
pica
l Med
icin
e (L
SH
TM),
UK
.
• D
ND
i P
roje
ct
Ma
na
ge
r: D
enis
Mar
tin
• P
roje
ct
sta
rt:
Dec
embe
r 20
05
8-am
inoq
uino
lines
are
a c
lass
of
com
poun
ds w
ith c
onsi
dera
ble
anti-
para
sitic
act
ivity
, but
thei
r po
tent
ial h
as
been
lim
ited
in th
e pa
st d
ue to
hum
an
toxi
city
. A te
am o
f res
earc
hers
led
by
the
Uni
vers
ity o
f Mis
siss
ippi
rece
ntly
de
velo
ped
NP
C11
61B
, a n
ew le
ad
com
poun
d fro
m th
e 8-
amin
oqui
nolin
e cl
ass,
whi
ch is
ver
y ef
fect
ive
agai
nst
para
site
s fo
r bo
th m
alar
ia a
nd
leis
hman
iasi
s, a
nd o
ffers
pro
mis
e fo
r re
duce
d he
mat
olog
ical
toxi
city
in m
an.
MM
V h
as b
een
wor
king
in c
olla
bora
tion
with
UM
to fu
rthe
r pr
eclin
ical
de
velo
pmen
t of N
PC
1161
B b
ecau
se
of p
rom
isin
g or
al e
ffi ca
cy a
gain
st P
. vi
vax
infe
ctio
n. T
hrou
gh a
coo
pera
tive
agre
emen
t, D
ND
i and
MM
V w
ill sh
are
clin
ical
info
rmat
ion,
as
wel
l as
sign
ifi ca
nt
scie
ntifi
c fi n
ding
s re
gard
ing
the
non-
clin
ical
saf
ety
data
, met
abol
ism
, or
othe
r re
leva
nt fi
ndin
gs. I
n 20
06, D
ND
i has
pr
ovid
ed fi
nanc
ial s
uppo
rt fo
r ad
ditio
nal
stud
ies
on th
e in
viv
o an
tilei
shm
ania
l/tr
ypan
osom
al a
ctiv
ity o
f NP
C11
61B
. D
ND
i will
unde
rgo
a re
view
pro
cess
w
ith it
s S
AC
in M
ay 2
007
to d
ecid
e w
heth
er to
pur
sue
this
pro
ject
or
othe
r 8-
amin
oqui
nolin
es fu
rthe
r ad
vanc
ed in
th
e dr
ug d
evel
opm
ent p
ipel
ine.
��� R
AV
UC
ON
AZ
OL
E
• T
arg
et
dis
ea
se
: C
haga
s di
seas
e
• P
art
ne
rs:
Fede
ral U
nive
rsity
of O
uro
Pre
to, B
razi
l; In
stitu
to V
enez
olan
o de
In
vest
igac
ione
s C
ient
ifi ca
s, V
enez
uela
; E
ISA
I Co.
Ltd
, Jap
an.
• D
ND
i P
roje
ct
Tea
m:
Rob
ert D
on, I
sabe
la R
ibei
ro
• P
roje
ct
sta
rt:
2005
Pre
clin
ical
stu
dies
with
ant
ifung
al tr
iazo
les
have
sho
wn
cons
ider
able
effi
cacy
in th
e tre
atm
ent o
f Cha
gas
dise
ase
in a
nim
al
mod
els.
Tw
o of
thes
e co
mpo
unds
hav
e be
en in
dev
elop
men
t for
fung
al in
fect
ions
: ra
vuco
nazo
le (E
isai
) is
curre
ntly
in P
hase
II
stud
ies,
and
pos
acon
azol
e (S
cher
ing
Plo
ugh)
was
rece
ntly
regi
ster
ed fo
r tre
atm
ent o
f fun
gal i
nfec
tions
in E
urop
e an
d as
an
antif
unga
l pro
phyl
actic
in th
e U
SA
. At t
he e
nd o
f 200
6, tw
o of
thre
e an
imal
stu
dies
hav
e be
en c
ompl
eted
w
ith ra
vuco
nazo
le to
fi nd
the
optim
um
dosi
ng re
gim
en, a
nd th
e th
ird h
as b
egun
(to
stu
dy b
i-dai
ly d
osin
g in
dog
s). I
n 20
07, t
he g
oal o
f the
tria
zole
pro
ject
is fo
r ei
ther
pos
acon
azol
e or
ravu
cona
zole
to
adva
nce
into
clin
ical
rese
arch
, if d
ata
and
cond
ition
s ar
e fa
vour
able
, and
to e
xam
ine
othe
r mol
ecul
es fr
om th
e sa
me
fam
ily a
s po
tent
ial d
rug
cand
idat
es.
DN
Di_
RA
_v23
.indd
16
28/0
9/07
20
:25:
42
02
. R
&D
Mo
de
l, S
tra
teg
y,
& P
or
tfo
lio
DNDi Annual Report 2006
17
Fin
din
g a
sa
fe a
nd
aff
ord
ab
le a
lte
rna
tive
���A
MP
HO
TE
RIC
IN B
PO
LY
ME
R
• T
arg
et
dis
ea
se
:vi
scer
al le
ishm
ania
sis
(VL)
• P
art
ne
rs:
Impe
rial C
olle
ge, U
K (P
rinci
pal I
nves
tigat
or);
Lond
on S
choo
l of P
harm
acy,
UK
; Lon
don
Sch
ool o
f Hyg
iene
and
Tr
opic
al M
edic
ine
(LS
HTM
), U
K; A
dvin
us, I
ndia
; Sha
nta
Bio
tech
, Ind
ia.
• D
ND
i P
roje
ct
Ma
na
ge
r:
Den
is M
artin
• P
roje
ct
sta
rt:
Sep
tem
ber
2006
Lipo
som
al a
mph
oter
icin
B (A
mB
isom
e), a
n ef
fi cac
ious
yet
hig
hly
expe
nsiv
e fo
rmul
atio
n of
am
phot
eric
in B
, has
bee
n in
crea
sing
ly u
sed
to tr
eat V
L. H
owev
er, i
ts u
se in
the
VL-
ende
mic
regi
ons
of A
frica
and
Asi
a ha
s be
en li
mite
d du
e its
hig
h co
st, w
hich
pric
es it
out
of u
se in
dev
elop
ing
coun
trie
s w
ith th
e hi
ghes
t bur
den
of d
isea
se. I
nste
ad, p
atie
nts
ther
e st
ill re
ceiv
e th
e ac
utel
y to
xic,
yet
mor
e af
ford
able
, am
phot
eric
in B
, a 7
0-ye
ar-o
ld d
rug
whi
ch k
ills 1
0% o
f the
pa
tient
s tr
eate
d w
ith it
. Thi
s pr
ojec
t aim
s to
com
bine
the
amph
oter
icin
mol
ecul
e in
a w
ay th
at is
sim
ilar
yet d
iffer
ent
from
the
way
Am
Bis
ome
is m
odifi
ed. I
nste
ad, i
n th
is p
roje
ct, a
mph
oter
icin
B w
ill be
sur
roun
ded
by a
less
exp
ensi
ve
met
hacr
ylic
aci
d de
rived
pol
ymer
, whi
ch is
exp
ecte
d to
mak
e a
drug
that
is s
tabl
e in
hot
clim
ates
, hig
hly
solu
ble,
re
lativ
ely
inex
pens
ive,
saf
e, a
nd e
ffect
ive
in s
hort
-ter
m th
erap
y of
VL.
The
ear
ly s
tage
pro
of-o
f-co
ncep
t of t
he
effi c
acy
of a
mod
ifi ed
met
acry
lic h
as b
een
show
n by
the
Impe
rial C
olle
ge te
am.
At t
he e
nd o
f 200
6, e
xper
imen
tal w
ork
has
begu
n in
in v
ivo
mou
se m
odel
s at
LS
HTM
, whe
re in
itial
effi
cacy
an
d sa
fety
dat
a lo
ok p
rom
isin
g. In
200
7, re
sear
cher
s w
ill op
timiz
e th
e in
vitr
o an
d ph
ysic
oche
mic
al p
rope
rtie
s of
th
e am
phot
eric
in-p
olym
er c
ompl
ex w
ith th
e ai
m to
hav
e a
wel
l-defi
ned
pol
ymer
wei
ght a
nd r
atio
bet
wee
n am
phot
eric
in B
and
pol
ymer
.
R&D Model, Strategy, & Portfolio
DN
Di_
RA
_v23
.indd
17
28/0
9/07
20
:25:
46
DNDi Annual Report 2006
18
R&D Model, Strategy & Portfolio
Th
e s
ix c
lin
ica
l p
roje
cts
in
DN
Di’
s p
ort
foli
o
at
the
en
d o
f 2
00
6 a
re m
ain
ly c
on
sti
tute
d o
f
a c
lus
ter
of
ne
w f
orm
ula
tio
ns
of
es
tab
lis
he
d
dru
gs
, d
rug
s s
wit
ch
ed
fro
m o
the
r in
dic
a-
tio
ns
, o
r d
rug
co
mb
ina
tio
ns
. W
hile
th
ere
are
few
no
vel
co
mp
ou
nd
s i
n t
his
are
a i
n R
&D
fo
r
neg
lect
ed
dis
ease
s, a
ll o
f th
e tre
atm
en
ts u
nd
er
inve
stig
ati
on
can
have
a r
eal i
mp
act
on
imp
rov-
ing
pa
tie
nt
tre
atm
en
t in
th
e n
ea
r fu
ture
an
d
se
rve
to
str
en
gth
en
cli
nic
al re
se
arc
h c
ap
acit
y
tha
t w
ill
be
use
d i
n t
he
fu
ture
fo
r e
valu
ati
ng
no
vel co
mp
ou
nd
s. T
wo
of th
e c
lin
ica
l p
roje
cts
,
wh
ich
are
cu
rren
tly
un
derg
oin
g th
e r
eg
istr
ati
on
pro
cess
, are
exp
ect
ed
to b
e a
vailab
le to p
ati
en
ts
in A
fric
a a
nd
La
tin
Am
eri
ca
in
20
07
.
Clin
ical
Pro
ject
s
���C
OM
BIN
AT
ION
TH
ER
AP
Y
• T
arg
et
dis
ea
se
:vi
scer
al le
ishm
ania
sis
(VL)
• P
art
ne
rs:
ICM
R, I
ndia
; Kal
a-az
ar M
edic
al
Res
earc
h C
entr
e, In
dia;
Raj
endr
a M
emor
ial R
esea
rch
Inst
itute
, Ind
ia;
Uni
vers
ity o
f Var
anas
i, In
dia
• D
ND
i P
roje
ct
Tea
m:
Cat
herin
e R
oyce
, Bha
wna
Sha
rma
• P
roje
ct
sta
rt:
Dec
embe
r 20
06
The
mos
t wid
ely
used
trea
tmen
t for
V
L is
sod
ium
stib
oglu
cona
te (S
SG
), w
hich
is to
xic,
diffi
cul
t to
use,
and
po
orly
tole
rate
d by
pat
ient
s. A
num
ber
of n
ew th
erap
eutic
opt
ions
hav
e be
en
deve
lope
d, b
ut th
ey a
re g
ener
ally
ex
pens
ive
and
ther
efor
e ca
nnot
be
adop
ted
by th
e m
ajor
ity o
f VL-
ende
mic
re
gion
s. A
t a m
eetin
g of
exp
erts
conv
ened
by
DN
Di i
n Fe
brua
ry 2
005,
a
num
ber
of k
ey d
river
s w
ere
iden
tifi e
d fo
r de
velo
ping
com
bina
tion
ther
apie
s fo
r V
L: e
ase
of u
se, s
hort
er c
ours
e of
trea
tmen
t, pr
even
tion
of p
aras
ite
resi
stan
ce, a
nd c
ost c
onta
inm
ent.
Add
ition
ally,
com
bina
tion
regi
men
s us
ing
alre
ady
exis
ting
drug
s of
fer
a sh
ort-
term
sol
utio
n to
ass
ist i
n pr
otec
ting
the
usef
ul li
fe o
f ava
ilabl
e dr
ugs
whi
le n
ew c
hem
ical
ent
ities
are
de
velo
ped.
The
refo
re, o
ne o
f the
crit
ical
is
sues
was
to u
tiliz
e dr
ugs
whi
ch a
re
alre
ady
regi
ster
ed in
the
regi
on (f
or
exam
ple,
Am
Bis
ome,
milt
efos
ine,
and
pa
rom
omyc
in w
hich
will
be u
sed
in
this
four
-arm
ed s
tudy
).
At t
he e
nd o
f 200
6, p
recl
inic
al s
tudi
es
for
effi c
acy
and
toxi
colo
gy h
ave
been
co
mpl
eted
. In
2007
, a p
roje
ct te
am
will
be a
ssem
bled
and
a c
linic
al s
tudy
pr
otoc
ol d
rafte
d in
the
fi rst
qua
rter
; and
by
the
end
of th
e ye
ar, p
atie
nt e
nrol
men
t w
ill be
initi
ated
.
���IM
IQU
IMO
D A
DJ
UN
CT
IM
MU
NO
TH
ER
AP
Y
• T
arg
et
dis
ea
se
: cu
tane
ous
leis
hman
iasi
s (C
L)
• P
art
ne
rs:
McG
ill U
nive
rsity
, Can
ada
(Prin
cipa
l in
vest
igat
or);
Uni
vers
idad
Per
uana
C
ayet
ano
Her
edia
, Per
u.
• D
ND
i P
roje
ct
Tea
m:
Cat
herin
e R
oyce
, Isa
bela
Rib
eiro
• P
roje
ct
sta
rt:
June
200
5
Cur
rent
trea
tmen
ts fo
r C
L ar
e ad
min
iste
red
syst
emat
ical
ly a
nd
requ
ire p
rotr
acte
d tr
eatm
ent b
y da
ily
intr
amus
cula
r in
ject
ions
. With
DN
Di’s
ul
timat
e go
al to
dev
elop
a b
ette
r to
lera
ted,
mor
e co
nven
ient
, and
ch
eape
r th
erap
y fo
r C
L th
an c
urre
nt
stan
dard
s, th
e st
udy
obje
ctiv
e is
to
dete
rmin
e th
e ef
fi cac
y an
d sa
fety
of
a to
pica
l adm
inis
trat
ion
of im
iqui
mod
, an
imm
unom
odul
ator
that
is u
sed
exte
nsiv
ely
as a
topi
cal t
reat
men
t for
ge
nita
l war
ts. I
miq
uim
od’s
mec
hani
sm
of a
ctio
n is
to s
timul
ate
a lo
cal i
mm
une
resp
onse
at t
he le
sion
site
and
ther
efor
e re
solv
e th
e in
fect
ion.
As
imiq
uim
od is
al
read
y av
aila
ble
as a
gen
eric
in a
few
co
untr
ies
with
end
emic
leis
hman
iasi
s,
it ha
s th
e po
tent
ial t
o be
a re
adily
af
ford
able
and
ava
ilabl
e tr
eatm
ent.
The
prim
ary
endp
oint
of t
he c
linic
al
stud
y, a
naly
sis
of 3
-mon
th fo
llow
-up
data
, was
mad
e in
Dec
embe
r 20
06.
In 2
007,
the
12-m
onth
follo
w-u
p da
ta
will
be a
vaila
ble.
DN
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51
DNDi Annual Report 2006
19 R&D Model, Strategy, & Portfolio
An
in
no
vati
ve p
art
ne
rsh
ip t
o b
rin
g h
op
e t
o A
fric
an
ma
lari
a p
ati
en
ts
02
. R
&D
Mo
de
l, S
tra
teg
y,
& P
or
tfo
lio
���A
SA
Q, F
IXE
D-D
OS
E A
RT
ES
UN
AT
E/A
MO
DIA
QU
INE
CO
MB
INA
TIO
N T
HE
RA
PY
• T
arg
et
dis
ea
se
: m
alar
ia
• P
art
ne
rs:
Cen
tre
Nat
iona
l de
Rec
herc
he e
t de
Form
atio
n su
r le
Pal
udis
me,
Bur
kina
Fas
o; U
nive
rsity
Sai
ns M
alay
sia;
Oxf
ord
Uni
vers
ity, U
K;
Mah
idol
Uni
vers
ity, T
haila
nd; T
ropi
val,
Fran
ce; E
llipse
Pha
rmac
eutic
als,
Fra
nce;
Rot
tend
orf P
harm
a,
Ger
man
y; M
édec
ins
San
s Fr
ontiè
res;
TD
R; s
anofi
-av
entis
.
• D
ND
i P
roje
ct
Tea
m:
Jean
-Ren
é K
iech
el, G
raci
ela
Dia
p
• P
roje
ct
sta
rt:
Janu
ary
2002
AS
AQ
, the
new
fi xe
d-do
se c
ombi
natio
n (F
DC
) of a
rtes
unat
e (A
S) a
nd a
mod
iaqu
ine
(AQ
), w
ill be
the
fi rst
dru
g to
be
deliv
ered
by
DN
Di a
nd is
inte
nded
to tr
eat p
aedi
atric
and
adu
lt un
com
plic
ated
falc
ipar
um m
alar
ia, w
ith a
prim
ary
focu
s on
Afri
ca a
nd s
ome
coun
trie
s in
Asi
a w
here
am
odia
quin
e re
sist
ance
is lo
w.
With
resi
stan
ce a
maj
or th
reat
to m
alar
ia c
ontr
ol, a
rtem
isin
in-b
ased
com
bina
tion
ther
apie
s (A
CTs
) offe
r a
way
to c
ount
er
resi
stan
ce: t
he c
ombi
natio
n of
AS
and
AQ
was
one
of f
our
AC
Ts re
com
men
ded
by W
HO
in 2
001
as fi
rst-
line
trea
tmen
t fo
r un
com
plic
ated
falc
ipar
um m
alar
ia, b
ut it
did
not
yet
exi
st a
s a
FDC
nor
was
it in
FD
C d
evel
opm
ent.
Hen
ce,
the
FAC
T (F
ixed
-Dos
e, A
rtes
unat
e-C
onta
inin
g Th
erap
y) P
roje
ct w
as u
nder
take
n in
200
2 by
a n
umbe
r of
pub
lic a
nd
priv
ate
part
ners
coo
rdin
ated
by
TDR
and
MS
F (w
ho tu
rned
ove
r th
e pr
ojec
t to
DN
Di u
pon
its fo
unda
tion)
.
AS
and
AQ
are
wel
l-kno
wn
drug
s, w
ith s
cien
tifi c
evi
denc
e su
ppor
ting
the
use
of th
e co
mbi
natio
n of
AS
and
AQ
in
appr
oxim
atel
y 10
,000
pat
ient
s. A
SA
Q p
rovi
des
a tr
ue in
nova
tion
in p
atie
nt tr
eatm
ent b
y be
ing
a tro
pica
l-sta
ble
bila
yer
cofo
rmul
atio
n w
hich
allo
ws
AS
and
AQ
to b
e ta
ken
toge
ther
and
in th
e co
rrec
t pro
port
ions
in a
sim
plifi
ed th
ree-
day
dosi
ng
regi
men
whe
re th
e m
ost v
ulne
rabl
e po
pula
tion,
chi
ldre
n un
der t
he a
ge o
f fi v
e, ta
ke o
ne ta
blet
per
day
.
In D
ecem
ber
2004
, san
ofi -
aven
tis s
igne
d on
as
indu
stria
l par
tner
and
has
bee
n in
volv
ed in
indu
stria
l, pr
eclin
ical
, and
cl
inic
al p
rodu
ct d
evel
opm
ent,
as w
ell a
s in
pre
para
tion
of a
ll of
the
regi
stra
tion
fi les
. AS
AQ
will
be a
qua
lity,
eas
y-to
-use
pr
oduc
t tha
t will
be re
adily
ava
ilabl
e an
d af
ford
able
at c
ost p
rice
(<U
S$1
for
adul
ts a
nd <
US
$0.5
0 fo
r ch
ildre
n in
pub
lic
mar
kets
) as
a no
n-pa
tent
ed p
ublic
goo
d.
The
year
200
6 w
as a
mile
ston
e ye
ar fo
r A
SA
Q: i
n Fe
brua
ry, t
he p
ivot
al P
hase
III fi
eld
stu
dy, w
hich
enr
olle
d 75
0 ch
ildre
n in
Bur
kina
Fas
o, s
ucce
ssfu
lly c
oncl
uded
and
sho
wed
fi na
l res
ults
of >
95%
effi
cacy
, whi
ch w
ere
pres
ente
d at
the
Am
eric
an S
ocie
ty fo
r Tr
opic
al M
edic
ine
and
Hyg
iene
(AS
TMH
) ann
ual m
eetin
g in
Nov
embe
r; a
lso
in N
ovem
ber,
sano
fi -av
entis
fi le
d fo
r re
gist
ratio
n in
Mor
occo
, the
cou
ntry
whe
re A
SA
Q is
man
ufac
ture
d.
2007
hol
ds g
reat
pro
mis
e as
the
next
ste
ps fo
r A
SA
Q a
re to
: obt
ain
regu
lato
ry a
ppro
val i
n M
oroc
co, u
nder
go
subm
issi
on fo
r W
HO
pre
qual
ifi ca
tion,
and
con
tinue
to b
e re
gist
ered
in a
ll su
b-S
ahar
an A
frica
n co
untr
ies
whe
re it
can
be
of s
ubst
antia
l pub
lic h
ealth
ben
efi t.
DN
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55
DNDi Annual Report 2006
20
Cli
nic
al
Pro
jec
ts
R&D Model, Strategy, & Portfolio
���F
IXE
D-D
OS
E A
RT
ES
UN
AT
E/
ME
FL
OQ
UIN
E (
AS
/MQ
) C
OM
BIN
AT
ION
TH
ER
AP
Y
FO
R M
AL
AR
IA
• T
arg
et
dis
ea
se
: m
alar
ia
• P
art
ne
rs:
Farm
angu
inho
s, B
razi
l; M
ahid
ol
Uni
vers
ity, T
haila
nd; S
hokl
o M
alar
ia
Res
earc
h U
nit,
Thai
land
; Uni
vers
ity
Sai
ns M
alay
sia;
Oxf
ord
Uni
vers
ity, U
K;
Méd
ecin
s S
ans
Fron
tière
s; T
DR
.
• D
ND
i P
roje
ct
Tea
m:
Jean
-Ren
é K
iech
el, I
sabe
la R
ibei
ro
• P
roje
ct
sta
rt:
Janu
ary
2002
Am
ong
the
mos
t stu
died
AC
Ts is
the
thre
e-da
y tr
eatm
ent w
ith a
rtes
unat
e (A
S) a
nd m
efl o
quin
e (M
Q),
whi
ch h
as
show
n to
be
a hi
ghly
effe
ctiv
e th
erap
y ag
ains
t unc
ompl
icat
ed m
alar
ia. A
SM
Q,
the
new
co-
form
ulat
ion
of A
S a
nd M
Q,
offe
rs a
sin
gle
daily
dos
e of
one
or
two
tabl
ets
over
thre
e da
ys a
nd p
rovi
des
adde
d re
gim
en s
impl
icity
.
Con
sist
ent w
ith 2
006
WH
O tr
eatm
ent
guid
elin
es, A
SM
Q w
ill se
rve
as a
fi x
ed-d
ose
com
bina
tion
to tr
eat
unco
mpl
icat
ed fa
lcip
arum
mal
aria
in
paed
iatr
ic a
nd n
on-p
regn
ant a
dult
popu
latio
ns. D
rug
depl
oym
ent e
ffort
s ar
e in
itial
ly fo
cuse
d on
are
as o
f low
tr
ansm
issi
on, i
nclu
ding
Sou
thea
st A
sia
and
Sou
th A
mer
ica,
but
AS
MQ
can
po
tent
ially
be
used
in a
ll en
dem
ic re
gion
s in
clud
ing
thos
e af
fect
ed b
y m
ulti-
drug
re
sist
ant P
. fal
cipa
rum
str
ains
.
In th
e ye
ar 2
006,
sig
nifi c
ant p
rogr
ess
was
mad
e. R
esul
ts w
ere
publ
ishe
d an
d sh
owed
the
effi c
acy
and
side
effe
ct
profi
le o
f AS
MQ
to b
e eq
uiva
lent
to th
e no
n-fi x
ed c
ombi
natio
n of
a P
hase
III
fi eld
stu
dy c
ondu
cted
in 5
00 p
atie
nts
in T
haila
nd in
200
5 (A
shle
y et
al.C
ID
2006
). In
Bra
zil,
a re
gist
ratio
n fi l
e w
as
subm
itted
to re
gula
tory
aut
horit
ies
in
Nov
embe
r by
Far
man
guin
hos,
the
FAC
T pr
oduc
tion
part
ner,
whi
ch is
a s
tate
-ow
ned
phar
mac
eutic
al c
ompa
ny. A
la
rge-
scal
e in
terv
entio
n st
udy
was
als
o un
dert
aken
by
the
Bra
zilia
n na
tiona
l co
ntro
l pro
gram
me.
The
futu
re h
olds
eve
n m
ore
prom
ise
for
AS
MQ
as
the
regi
stra
tion
proc
ess
cont
inue
s an
d ex
tend
s to
oth
er
coun
trie
s in
Lat
in A
mer
ica,
a fi
le w
ill be
su
bmitt
ed fo
r W
HO
pre
-qua
lifi c
atio
n,
and
SE
Asi
an a
utho
ritie
s an
d an
in
dust
rial p
artn
er w
ill be
iden
tifi e
d an
d en
gage
d to
faci
litat
e re
gion
al
impl
emen
tatio
n of
one
of t
he w
orld
’s
mos
t effe
ctiv
e tr
eatm
ents
for
mal
aria
.
��� N
IFU
RT
IMO
X-E
FL
OR
NIT
HIN
E
CO
-AD
MIN
IST
RA
TIO
N
• T
arg
et
dis
ea
se
: hu
man
Afri
can
tryp
anos
omia
sis
(HAT
)
• P
art
ne
rs:
Epi
cent
re, F
ranc
e; M
édec
ins
San
s Fr
ontiè
res-
Bel
gium
; Méd
ecin
s S
ans
Fron
tière
s-H
olla
nd, t
he n
atio
nal H
AT
cont
rol p
rogr
amm
es o
f the
Dem
ocra
tic
Rep
ublic
of C
ongo
(DR
C),
the
Rep
ublic
of
Con
go, U
gand
a; S
wis
s Tr
opic
al
Inst
itute
, Sw
itzer
land
; TD
R.
• D
ND
i P
roje
ct
Ma
na
ge
r:
Els
Tor
reel
e
• P
roje
ct
sta
rt:
2003
NE
CT
is a
mul
ti-ce
ntre
clin
ical
stu
dy
to t
est
a si
mpl
ifi ed
com
bina
tion
of
nifu
rtim
ox a
nd e
fl orn
ithin
e (N
EC
) for
st
age
2 H
AT. B
egun
as
a si
ngle
cen
ter
stud
y by
MS
F-H
olla
nd a
nd E
pice
ntre
in
the
Rep
ublic
of C
ongo
in 2
003,
the
st
udy
obje
ctiv
e is
to
dem
onst
rate
tha
t th
e co
mbi
natio
n is
as
effe
ctiv
e an
d sa
fe
as s
tand
ard
efl o
rnith
ine
mon
othe
rapy
, bu
t ea
sier
to
use,
as
the
num
ber
of
slow
, int
rave
nous
infu
sion
s of
nifu
rtim
ox
is r
educ
ed fr
om 5
6 to
14.
The
ulti
mat
e go
al is
to
build
an
evid
ence
bas
e on
th
e sa
fety
and
effi
cacy
of N
EC
as
a ne
w fi
rst
line
trea
tmen
t su
fferin
g fro
m
stag
e 2
HAT
, so
as t
o en
able
a W
HO
re
com
men
datio
n on
its
use.
Sin
ce 2
005,
DN
Di’s
act
iviti
es h
ave
mai
nly
focu
sed
on t
he im
plem
enta
tion
of t
his
stud
y at
thr
ee s
ites
in D
RC
(in
clud
ing
thei
r re
habi
litat
ion
and
equi
pmen
t) to
com
plem
ent
the
data
of
the
initi
al N
EC
T st
udy
in C
ongo
-B
razz
aville
, whe
re p
atie
nt n
umbe
rs
wer
e in
suffi
cien
t to
com
plet
e th
e st
udy.
At
the
end
of 2
006,
pat
ient
rec
ruitm
ent
at th
e th
ree
DN
Di s
ites
in D
RC
w
as c
ompl
eted
afte
r re
achi
ng t
he
280
patie
nt t
arge
t fo
r th
e tr
ial (
whe
n ta
king
acc
ount
the
num
ber
of p
atie
nts
enro
lled
at t
he C
ongo
-Bra
zzav
ile s
ite).
A fu
ll sa
fety
ana
lysi
s w
ill be
com
plet
ed
by m
id 2
007.
Fin
al r
esul
ts o
f the
tria
l, in
clud
ing
the
effi c
acy
anal
ysis
at
the
18-m
onth
follo
w-u
p, a
re e
xpec
ted
by
the
four
th q
uart
er o
f 200
8.
���P
AR
OM
OM
YC
IN
FO
R A
FR
ICA
• T
arg
et
dis
ea
se
: vi
scer
al le
ishm
ania
sis
• P
art
ne
rs:
Ken
ya M
edic
al R
esea
rch
Inst
itute
, K
enya
; Uni
vers
ity o
f Nai
robi
, Ken
ya;
Uni
vers
ity o
f Add
is A
baba
, Eth
iopi
a;
Inst
itute
of E
ndem
ic D
isea
ses,
U
nive
rsity
of K
hart
oum
, Sud
an;
Ged
aref
Uni
vers
ity, S
udan
; Nat
iona
l R
ibat
Uni
vers
ity, S
udan
; ID
A; M
édec
ins
San
s Fr
ontiè
res-
Hol
land
; TD
R; L
ondo
n S
choo
l of H
ygie
ne a
nd T
ropi
cal
Med
icin
e, U
K.
• D
ND
i P
roje
ct
Tea
m:
Cat
herin
e R
oyce
, Sal
ly E
llis
• P
roje
ct
sta
rt:
Nov
embe
r 20
04
Par
omom
ycin
, an
amin
ogly
cosi
de
antib
iotic
that
was
iden
tifi e
d in
the
1960
s as
an
antil
eish
man
ial,
repr
esen
ts
an im
prov
ed tr
eatm
ent a
t a lo
wer
co
st th
at w
ill al
low
it to
be
adop
ted
in d
evel
opin
g co
untr
ies
suffe
ring
the
larg
est d
isea
se b
urde
n of
VL.
A c
ritic
al
mile
ston
e w
as m
et fo
r pa
rom
omyc
in
deve
lopm
ent i
n 20
06 a
s ou
r pa
rtne
r P
DP,
the
inst
itute
for
One
Wor
ld
Hea
lth (i
OW
H),
succ
essf
ully
regi
ster
ed
paro
mom
ycin
intr
amus
cula
r (IM
) in
ject
ion
in In
dia
in A
ugus
t.
As
iOW
H w
orks
to m
ake
paro
mom
ycin
av
aila
ble
on th
e In
dian
sub
-con
tinen
t, D
ND
i is
wor
king
in p
aral
lel w
ith th
e Le
ishm
ania
sis
Eas
t Afri
ca P
latfo
rm
(LE
AP
) to
stud
y th
e ef
fi cac
y an
d sa
fety
of
par
omom
ycin
in A
frica
, spe
cifi c
ally
in
Eth
iopi
a, K
enya
, Sud
an. T
he a
im
DN
Di_
RA
_v23
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20
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02
DNDi Annual Report 2006
21 R&D Model, Strategy, & Portfolio
is to
regi
ster
par
omom
ycin
as
a ne
w tr
eatm
ent i
n ea
ch re
gion
and
to
have
it a
dopt
ed in
nat
iona
l tre
atm
ent
guid
elin
es.
At t
he e
nd o
f 200
6, th
e st
udy
is
curr
ently
recr
uitin
g pa
tient
s at
six
site
s in
Eth
iopi
a, K
enya
, and
Sud
an, fi
ve
site
s w
here
infra
stru
ctur
e ha
s be
en
impr
oved
or
built
(as
in th
e ca
se o
f the
Le
ishm
ania
sis
Trea
tmen
t and
Res
earc
h C
entr
e bu
ilt b
y D
ND
i & L
EA
P in
Arb
a M
inch
, Eth
iopi
a). T
he n
ext s
tep
for
the
proj
ect w
ill be
an
inte
rim a
naly
sis
to b
e co
nclu
ded
by e
arly
200
8.
���A
MB
ISO
ME
• T
arg
et
dis
ea
se
: vi
scer
al le
ishm
ania
sis
(VL)
• P
art
ne
rs:
Add
is A
baba
Uni
vers
ity, E
thio
pia;
Lo
ndon
Sch
ool o
f Hyg
iene
and
Tro
pica
l M
edic
ine,
UK
.
• D
ND
i P
roje
ct
Ma
na
ge
r:
Cat
herin
e R
oyce
• P
roje
ct
sta
rt:
upon
com
plet
ion
of th
e pa
rom
omyc
in s
tudy
Am
Bis
ome,
a li
poso
mal
form
ulat
ion
of a
mph
oter
icin
B m
anuf
actu
red
by
Gile
ad, h
as b
een
used
with
incr
easi
ng
frequ
ency
to tr
eat V
L, e
spec
ially
in
Eur
ope,
ove
r th
e pa
st d
ecad
e.
Unf
ortu
nate
ly, in
Afri
ca a
nd A
sia,
whe
re
dise
ase
burd
en is
hig
h, d
rug
acce
ss is
po
or b
ecau
se o
f the
hig
h co
st o
f the
dr
ug. W
ith re
cent
pre
fere
ntia
l pric
ing
offe
red
by th
e m
anuf
actu
rer
to p
atie
nts
in th
e pu
blic
sec
tor
in E
ast A
frica
, the
re
is a
pos
sibi
lity
that
Am
Bis
ome
coul
d be
com
e ec
onom
ical
ly fe
asib
le fo
r fi r
st-
line
trea
tmen
t, ev
en in
reso
urce
-poo
r co
untr
ies.
The
goal
of t
his
proj
ect,
ther
efor
e, is
to
det
erm
ine
the
min
imum
dos
e of
A
mB
isom
e th
at is
effi
caci
ous,
saf
e, a
nd
cost
effe
ctiv
e in
the
trea
tmen
t of V
L,
to re
duce
leng
th o
f hos
pita
l sta
y, a
nd
to fa
cilit
ate
regi
stra
tion
and
adop
tion
of A
mB
isom
e in
Eth
iopi
a. Id
entif
ying
th
e m
inim
um d
ose
for
mon
othe
rapy
w
ill be
an
impo
rtan
t ste
p in
dev
elop
ing
com
bina
tions
for
Afri
ca.
02
. R
&D
Mo
de
l, S
tra
teg
y,
& P
or
tfo
lio
DN
Di_
RA
_v23
.indd
21
28/0
9/07
20
:26:
17
