The Discovery of the FGFR clinical compound AZD4547. A presentation at a University of East Anglia Summer School

1. The discovery of AZD4547:
An orally bioavailable, potent and
selective N-(5-Pyrazolyl)
benzamide FGFR1-3 inhibitor
David Andrews
AstraZeneca
27th June 2014
AnorcQ Industrial Summer School

2. 2
FGF / FGFR signaling
FGFR2 FGFR3
FGFR1
P P
P P
P P
P P
FGFR4
18 secreted ligands
4 non-secreted ligands
Proliferation / migration /
anti-apoptosis / angiogenesis
Four FGF receptors,
FGFR1-4, but multiple splice
variants in extracellular
ligand binding domain create
many more receptor
isoforms with different ligand
binding specificities
Targeting FGFR kinase inhibition the four receptors have different,
but highly homogous, kinase domains

3. 3
FGF / FGFR signaling
FGFR2 FGFR3
FGFR1
18 secreted ligands
4 non-secreted ligands
P PP P
P PP P
FGFR4
whole kinase domain sequence homology (276-277
residues)
FGFR1 FGFR2 FGFR3 FGFR4
FGFR1 100%
FGFR2 88% 100%
FGFR3 86% 89% 100%
FGFR4 77% 78% 81% 100%
"key" ATP site homology (81 residues)
FGFR1 FGFR2 FGFR3 FGFR4
FGFR1 100%
FGFR2 94% 100%
FGFR3 91% 90% 100%
FGFR4 89% 89% 93% 100%

4. Early pharmacological tools –
Parke Davis FGFR inhibitors
4
N
N N
O
O
NH
HN O
HN
N
N
N N
O
O
NH
HN O
H2N
PD166866 PD173074
J. Pharmacol. Exp. Ther. 1998, 286(1), 569
J. Med. Chem. 1998, 41(11), 1752
J. Med. Chem. 1997, 40(15), 2296
Bioorg. Med. Chem. Lett. 1997, 7(18), 2415

5. Binding mode of PD173074
5
N
N N
O
O
NH
HN O
HN
N
PD173074
Crystal structure of an angiogenesis inhibitor bound to the FGF
receptor tyrosine kinase domain
EMBO J 1998, 17(20): 5896

6. VEGFR & FGFR kinase inhibitor drugs in clinical
development
6
F NH2 N N N
NH
NH
O TKI258
Dovitinib
O
N
N
N H
F
N
O
TKI258 / Docitinib: Blood 2005, 105, 2941
BIBF 1120 / Intedanib: Cancer Res. 2008, 68, 4774
BMS-582664: Brivanib alaninate: Clin. Cancer Res. 2008, 14, 6146
O
O
O
H2N
BMS-582664
Brivanib alaninate
NH
NH
N N
N
O
O
O
BIBF-1120
Intedanib
Phase III
Renal cell cancer Phase III
Non-small cell lung cancer
Ovarian cancer.
Phase III
Hepatocellular cancer.
Colorectal cancer

7. 7
Aberrant regulation of FGF/FGFR signaling
occurs in many human tumors
FGFR2 FGFR3
FGFR1
P P
P P
P P
P P
Non-invasive bladder cancer
Mutations ~70% tumors
Multiple myeloma
Translocation ~20% tumors
FGFR4
18 ligands
Proliferation / migration /
anti-apoptosis / angiogenesis
Colorectal and
Hepatocellular cancer
Up-regulated FGF19
Gastric cancer
Amplification ~5% tumors
Endometrial cancer
Mutations ~15%
Breast cancer
Amplification ~10% ER +ve
Squamous NSCLC
Amplification ~15%
Prostate (FGFR1 and 4)
Up-regulated FGFR4 and
FGF ligands

8. Recently reported FGFR inhibitors
8
N
N
N
O
N
H
Cl
Cl
O
O
NH
N
N
NVP-BGJ398
IC50 nM
FGFR1 0.9
FGFR2 1.4
FGFR3 1.0
FGFR4 60
KDR 180
BGJ398 J. Med. Chem. 2011, 54, 7066 LY2874455 Mol Cancer Ther 2011, 10(11):
2200
N
Cl
Cl
O
NH
N
N
N
HO
LY2874455
IC50 nM
FGFR1 2.8
FGFR2 2.6
FGFR3 3.4
FGFR4 6
KDR 7

9. Identification of AZ FGFR hit compounds
9
Screening of compounds prepared in an IGF1R TKI project in a kinase panel
highlighted some pyrazolylaminopyrimidines that were more potent against
FGFR than other kinases in the panel.
A key project aim was to identify compounds that are selective inhibitors of
FGFR suitable for in vivo testing in order to identify FGFR driven effects. In
particular this meant selectivity with respect to VEGFR.
Crystal structure and SAR analysis was used to guide chemistry to achieve
desired selectivity goal.
N
N
N
NH
N
N H
Br
H
O N
RA Norman, A-K Schott, DM Andrews, J Breed, KM Foote, AP
Garner, et al Protein-ligand crystal structures can guide the
design of selective inhibitors of the FGFR Tyrosine Kinase.
2012. J. Med. Chem. 55 (11), pp 5003–5012

10. Pyrazolylaminopyrimidines SAR (1)
10
N
N
N
N H
N
NH
R1
Br
H
Cpd R1 FGFR1
enzyme
KDR
enzyme
IGF1R
enzyme
1 540 590 6000
2 670 920 4200
3 69 680 7800
O N
4 32 3600 9100
O N
N
IC50 (nM)

11. Pyrazolylaminopyrimidines SAR (2)
11
N
N
HN
N H
N
R2
NH
Br
N
O
Cpd R2 FGFR1
enzyme
IC50 (nM)
KDR
enzyme
IGF1R
enzyme
3 Me 69 680 7800
5 57 1100 18000
O
6 9.8 150 370
7 2.4 23 6800

12. Early hit SAR: Compound 7
12
N
N
HN
N H
N
NH
Br
N
O
ClogP 4.3
Aqueous Solubility pH7.4 (mM) 1.8
PPB (% Free) rat / man 0.6 / 0.1
Hep Metabol Clint (μl/min/1E6) rat / man 118 / 259
CYP IC50 1A2 / 3A4 / 2C9 / 2C19 / 2D6 (mM) <0.1 / 0.23 / 0.75 / 0.99 / >10

13. Pyrazolylaminopyrimidines SAR (3)
13
Cpd X R2
FGFR1
enzyme
IC50 (nM)
pFGFR1 cell
assay IC50
(nM)
LogD
8 Br cPr 50 - 3.4
9 Cl cPr 40 - 3.3
10 H cPr 40 - 2.5 *
11 H 1.8 60 3.1
R2
N
HN
N H
N N
HN
O
N
X
MeO
OMe
* estimated
Compound 11 properties
hERG IC50 (mM) 8.4
Aqueous Solubility pH7.4 (mM) 0.58
Hep Metabol Clint (μl/min/1E6) rat 44
CYP IC50 1A2 / 3A4 / 2C9 / 2C19 / 2D6 (mM) >10 / <0.1 / 2.6 / >10 / >10

14. Pyrazolylaminopyrimidines summary
and next steps…..
14
• Pyrazolylaminopyrimidines inhibitors provided potent and selective
FGFR inhibitors and understanding of SAR.
• However the physical and ADME properties of the more potent
pyrazolylaminopyrimidines were far from acceptable.
• To improve on these aminopyrazole based inhibitors of FGFR1, we
sought to identify alternative compounds, containing this key hinge
binding motif, that could provide a less intrinsically lipophilic start point
for developing FGFR inhibitors.
• As part of this effort, compound 12 was synthesized and found to be
a sub-micromolar inhibitor of FGFR1
HN N
N H
Compound 12 N N
O

15. N-(5-Pyrazolyl)benzamide SAR
15
Cpd R1
FGFR1
enzyme IC50
(nM)
pFGFR1 cell
assay IC50
(nM)
LogD Aq. Sol.
(mM)
12 cPr 66 610 2.4 * -
13 MeO
0.7 19 3.1 27
OMe
O
14 0.9 6.0 3.2 1.4
MeO
OMe
* estimated
R1
N
HN
N H
O
N
N

16. Characterization of lead pyrazolylbenzamide
Compound 13
17
N
HN
N H
MeO OMe
N
O
N
FGFR1
enzyme
IC50 (nM)
KDR enzyme
IC50 (nM)
pFGFR1 cell
assay IC50
(mM)
pKDR cell
assay IC50
(mM)
0.7 210 0.019 0.24
LogD
pH7.4
Aq. Sol.
pH7.4 (mM)
PPB rat /hu
(%free) pKa hERG IC50
(mM)
3.1 27 3.4 / 5.7 7.6 >30
CYP inhibition IC50 (mM)
1A2 3A4 2C9 2C19 2D6
>10 7.5 >10 >10 >10
Hydrolytic stability T1/2 (days)
pH 1 pH 4 pH 6 pH 8 pH 10
43 >1000 >1000 375 223

17. Characterization of lead pyrazolylbenzamide
Compound 13
18
MeO
OMe
N
N H
HN
O
N
N

18. Characterization of lead pyrazolylbenzamide
Compound 13
19
30
25
20
15
10
5
0
Kinase selectivity screening
(Dundee consortiumpanel)
compd 6: 1μM, ATP: Km
<10 10-20 20-30 30-40 40-50 50-60 60-70 70-80 80-90 >90
Count of kinases in inhibition band
% inhibition
FGFR1
MeO
OMe
N
N H
HN
O
N
N

19. Characterization of lead pyrazolylbenzamide
Compound 13
20
N
HN
N H
MeO OMe
N
O
N
Models of metabolism Models of absorption
Rat heps
Clint
(ml/min/106)
Human heps
Clint
(ml/min/106)
MDCK AtoB
pApp (cm/s) MDCK BtoA
pApp (cm/s)
60 8.1 10.5 x10-6 12.2 x10-6
In vivo PK
Species
(media)
Cl
(ml/min/kg) Vss (l/kg)
Oral
bioavailability
(%)
Rat (plasma) 46 3.9 50
Dog (blood) 12 1.3 30
Main site of metabolism identified as terminal NMe of piperidine:
Oxidative demethylation and N-oxidation

20. Pyrazolylbenzamide SAR: piperazine variation
21
X
MeO
OMe
HN N
N H
O
Het
Cpd X Het
FGFR1
enzyme IC50
(nM)
pFGFR1 cell
assay IC50 (nM)
Solvent
LogD
pH7.4
Aq. Sol.
pH7.4
(mM)
N
13 CH2 N
0.7 19 3.1 27
N
14 O N
0.9 6 3.2 1.4
N
NH
16 CH2 0.9 17 1.8 37
N H
17 O N
1.7 17 1.9 56
N
18 CH2 1.6 11 2.3 372

21. Characterization of lead pyrazolylbenzamide
Compound 13
22
MeO
OMe
N
N H
HN
O
N
N

22. 23
Pyrazolylbenzamide SAR: piperazine variation
Cpd pKa
MeO
OMe
MDCK
AtoB pApp
(cm/s)
X
HN N
Rat heps
Clint
(ml/min/106)
Het
Rat Cl
(ml/min/kg) #
Rat Vss
(l/kg) #
Rat oral
bioavail
. (%) #
N H
O
13 7.6 10.5 x10-6 60 46 3.9 50
14 7.6 * 7.3 x10-6 75 - - -
16 8.6 4.1 x10-6 12 23 5.6 3
17 9.1 4.2 x10-6 7.2 7.8 1.8 4
18 9.2 5.2 x10-6 <3.9 59 11.7 16
Het groups 13 & 14 N N
16 N
NH 17
N H
N 18
N

23. Pyrazolylbenzamide summary
and next steps…..
24
Representative compounds in the pyrazolylbenzamide series fall
into two groups:-
•Those with moderate/high clearance and reasonable
bioavailability,
• associated with lower pKa, higher LogD and higher
permeability
and
•Those with low clearance but with low oral bioavailability,
• associated with higher pKa, lower LogD and lower
permeability.

24. Pyrazolylbenzamide summary
and next steps…..
25
Hypothesis
• Metabolism appears to be blocked by protonation of the terminal
nitrogen. Higher pKa compounds show lower intrinsic clearance.
• However compounds with higher pKa, lower LogD, and/or higher
NH donor count appear to show poor absorption.
Proposal
• Explore N-alkyl heterocycle with moderated pKa and LogD.
(increased pKa and lower LogD).
• Explore NH heterocycles with increased lipophilicity and potential
to sterically “mask” the polar NH group.

25. Optimal pyrazolylbenzamides
26
Cpd FGFR1 enzyme
IC50 (nM)
pFGFR1 cell
assay IC50 (nM)
Cpd 19 Cpd 20
LogD
pH7.4
Aq. Sol.
pH7.4 (mM) pKa
19 0.2 12 2.4 157 8.5
20 0.5 12 3.0 * 148 8.7
Cpd Rat heps
Clint (ml/min/106)
Human heps
Clint
(ml/min/106)
Rat PK
medium
Rat Cl
(ml/min/kg)
Rat Vss
(l/kg)
Rat oral
bioavail. (%)
19 11 <6.1 plasma 16 3.4 54
20 9.7 <4.1 blood 13 1.7 46
* Estimated
MeO
OMe
N
N H N H
O
Het
N
NH N O
Het =

26. Optimal pyrazolylbenzamides
27
MeO
OMe
N
N H N H
O
N
NH
Compound 19 was selected for progression to
clinical development and given the development
code AZD4547

27. AZD4547 Discovery Synthetic Route
28
O
O
N H
N
O NH
N
NH
O
O
N
N
NH2
O
O
O
N
NH
O
N
O
O
O
O
O
O
O
N
O
O
N
NH
NH2
O O
F
N H
NH
NaHMDS
THF
+
NaH
Toluene
NH2NH2
EtOH
(BOC)2O
CH2Cl2
heat,
DMSO
+

28. AZD4547 Discovery Synthetic Route
29
O
O
N H
N
O NH
N
NH
O
O
N
N
NH2
O
O
O
N
NH
O
N
O
O
O
O
O
O
O
N
O
O
N
NH
NH2
O O
F
N H
NH
NaHMDS
THF
+
NaH
Toluene
NH2NH2
EtOH
(BOC)2O
CH2Cl2
heat,
DMSO
+

29. AZD4547 Discovery Synthetic Route
30
O
O
N H
N
O NH
N
NH
O
O
N
N
NH2
O
O
O
N
NH
O
N
O
O
O
O
O
O
O
N
O
O
N
NH
NH2
O O
F
N H
NH
NaHMDS
THF
+
NaH
Toluene
NH2NH2
EtOH
(BOC)2O
CH2Cl2
heat,
DMSO
+

30. 31
AZD4547 Characterization
• AZD4547 is a potent and selective inhibitor of
FGFR 1, 2 and 3 receptor tyrosine kinases
FGFR1 FGFR2 FGFR3 FGFR4 KDR IGFR
Enzyme
IC50 (nM) 0.2 2.5 1.8 165 24 581
Cell IC50 (nM) 13 2 40 142 258 829

31. 32
Drug properties
Parameter AZD4547
Mol. Weight 463.6
Aq solubility (μM) 157
LogD 2.4
Form Crystalline, stable
Protein binding (% free; mouse, rat, rabbit, dog, human) 0.7,1.8, 0.3, 2.9, 2.1
Blood clearance (ml/min/kg; rat, dog) 39, 13
Blood Vdss (l/kg; rat, dog) 6, 5
Bioavailability (%; rat, dog) 42–100
In vitro hepatocyte clearance (ml/min/106 cells; rat, dog, human) 12, <4.4, ≤8.6
CYP inhibition IC50 (μM at 1A2, 2A6, 2E1, 2B6, 2C8, 2C9, 2C19,
All >10
2D6, 3A4)
Ames Negative
Mouse lymphoma Negative
hERG (mM) >33

32. 33
Genetic dysregulation of FGFR confers
sensitivity to AZD4547 in tumor cell lines
KG1a
Sum52-PE
KMS11
kDa
76-
52-
225-
150-
102-
225-
150-
102-
52-
38-
31-
MCF7
FGFR1
FGFR2
FGFR3
GAPDH
Tumor
cell line
Deregulated FGFR
member/mechanism
Proliferation
IC50 (μM) SEM
KG1a FGFR1 – Gene fusion 0.018 (n=3) 0.0017
SUM52-
FGFR2 – Gene
PE
amplification 0.041 (n=4) 0.0185
KMS11
FGFR3 – Translocation
(t4;14) and mutation
(Y373C)
0.281 (n=5) 0.0294
MCF7 None >30 (n=6) NA

33. 34
AZD4547 induces dose-dependent efficacy in
the KMS-II multiple myeloma xenograft model
Control
3 mg/kg qd
3 mg/kg bid
6.25 mg/kg qd
6.25 mg/kg bid
12.5 mg/kg qd
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
Control
AZD4547 12.5mg/kg qd
AZD4547 6.25mg/kg qd
AZD4547 6.25mg/kg bid
AZD4547 3mg/kg qd
AZD4547 3mg/kg bid
• Dose-dependent antitumor activity at well tolerated doses
• Maximum efficacious doses – 12.5 mg/kg qd/6.25 mg/kg
bid
• Efficacy is linked to to AUC rather than CMAX
NS
–53%***
–70%***
–98%***
–100%***
0 5 10 15 20 25
0.2
Mean Tumour volume (cm3) +/- SEM
Days of Treatment
Mean tumor volume (cm3) ± SEM

34. 35
AZD4547 reverses a bFGF driven angiogenic
phenotype
Vessel formation in vitro
Control media bFGF (5 ng/ml)
bFGF (5 ng/ml) +
AZD4547 (100 nM)
Vessel formation in vivo
Matrigel plug assay – mean vessel density
0.6
0.5
0.4
0.3
0.2
0.1
0
Control bFGF
(1 μg/ml)
bFGF +
AZD4547
(6.25 mg/kg bid)
MVD per 5000 μm2

35. 36
AZD4547 in vivo tumor efficacy is not
attributable to inhibition of KDR
AZD4547 is inactive in KDR-sensitive
xenograft models
Tumor
model
Dose
(mg/kg)
Frequency of
dosing
Inhibition
of tumor growth
(%)
Calu-6 6.25 bid 0
LoVo 6.25 bid 0
HCT-15 6.25 bid 4.7
AZD4547 has no effect on vessel
growth in KMS11 tumors
Control AZD4547
(7 days at 6.25 mg/kg bid)
CD31 Staining
Calu-6
Control
Cediranib 3 mg/kg qd
AZD4547 6.25 mg/kg bid
–2 0 2 4 6 8 10 12 14 16 18
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
Mean tumor volume (cm3) ± SEM
Days of treatment

36. 37
FGFR2 gene amplified gastric cancer cells are
very sensitive to AZD4547
Sensitivity of gastric cancer cells to AZD4547
in MTS assay
100
10
1
0.1
0.01
0.001
GI50 (μM)
GC lines

37. 38
AZD4547 causes dose-dependent tumor growth
inhibition in Snu-16 gastric xenograft model
Model
FGFR2 expression % TGI by AZD4547
FISH Affy 12.5
mg/kg qd
AZD4547 1.56 mg/kg qd po
AZD4547 3.125 mg/kg qd po
• Dose-dependent antitumor efficacy of AZD4547 at well tolerated doses
• Evidence of tumor regression at 12.5 mg/kg qd
• Efficacy of AZD4547 is greater in the Snu-16 model than in gastric cancer
xenograft models with normal FGFR2 gene copy number (FISH = 1)
25
mg/kg qd
Snu-16 6 +++ > 100 N/A
AZ521 1 +++ 63 77
MGC803 1 +++ 45 72
1000
0
Treatment period (day)
800
3
600
400
6 10 13 17 20 24 27
Tumor volume (mm3)
0
AZD4547 6.25 mg/kg qd po
AZD4547 12.5 mg/kg qd po
200
Vehicle control

38. AZD4547 is significantly more efficacious in
gastric cancer primary models with FGFR2 gene
amplification
GC model ID SGC100 SGC031 G009 SGC001 G001 SGC020 SGC002 SGC110 SGC105 SGC083
39
FGFR2 FISH
score
1
Disomy
2
Trisomy
3
Trisomy
3
Trisomy
4
Poly-somy
5
Poly-somy
5
Poly-somy
5
Poly-somy
5
Poly-somy
6
Gene
Amplifi-cation
FGFR2 FISH
GCN 1.8 2.2 2.6 2.6 3.3 2.6 3.6 4 4.9 30
Western Blot ++ + + +++ + + + ++ + ++++++
In vivo %TGI
(25mg/kg/qd)
26
(P=0.030)
7
(P=0.419)
44
(P=0.004)
98
(P=<0.0001)
76
(P=<0.00
01)
25
(P=0.143)
26
(P=0.053)
14
(P=0.120)
10
(P=0.288)
162
(P=<0.0001)

39. AZD4547 is efficacious against FGFR1-amplified
squamous cell lung cancer primary models.
900
800
700
600
500
400
300
Tumor 200
0 3 0 3 Tumor 40
Model
ID:
FGFR1 IHC
(IHC score
embedded)
L123 LC038 LC026 LC036
++
+
Score
6
++
+
++
+
-
ve
Score
6
Score
6
Score
1
FGFR1 FISH
(FISH score
embedded)
1,200
Efficacy study of AZD4547 in L123
1,200
1,000
1,000
800
800
600
600
400
400
200
200
0
Efficacy study of AZD4547 in L123
G1: Vehicle control
G2: AZD4547 25 mg/kg/qd
G1: Vehicle control
G2: AZD4547 25 mg/kg/qd
0 2 4 6 8 10 12 14
Tumor volume/m^3)
Treatment period (days)
0
0 2 4 6 8 10 12 14
Tumor volume/m^3)
Treatment period (days)
1,200
1,200
1,000
1,000
800
800
600
600
400
400
200
200
0
Efficacy study of AZD4547 in LC038
Efficacy study of AZD4547 in LC038
Vehicle control
AZD4547 25mg/kg/qd p.o
Vehicle control
AZD4547 25mg/kg/qd p.o
0 7 14 21 28
Tumor Volume (m3)
Treatment period (Days)
0
0 7 14 21 28
Tumor Volume (m3)
Treatment period (Days)
1,200
1,200
1,000
1,000
800
800
600
600
400
400
200
200
0
Efficacy study of AZD4547 in LC026
Efficacy study of AZD4547 in LC026
G1: Vehicle control
G2: AZD4547 25mg/kg/qd
G1: Vehicle control
G2: AZD4547 25mg/kg/qd
0 2 4 6 8 10 12 14 16 18 20 22
Treatment period (days)
0
0 2 4 6 8 10 12 14 16 18 20 22
Tumor Volume (m3)
Treatment period (days)
800
800
700
700
600
600
500
500
400
400
300
300
200
200
100
100
0
AZD4547 TGI in LC036F4
AZD4547 TGI in LC036F4
G1: vehicle control
G2: AZD4547: 12.5mg/kg
G3: AZD4547: 25mg/kg
G1: vehicle control
G2: AZD4547: 12.5mg/kg
G3: AZD4547: 25mg/kg
0 3 6 9 12 15 18 21
Tumor Volume (m3)
Treatment Period (days)
900
800
700
600
500
400
300
200
100
100
0
Volume (m3)
AZD4547 G1: G2: G3: Treatment 0
0 3 6 9 12 15 18 21
Tumor Volume (m3)
Treatment Period (days)
0
Volume (m3)
AZD4547 G1: G2: G3: Treatment

40. 41
Summary
• Pyrazolylaminopyrimidine hits provided key understanding of SAR and
binding interactions leading to potent and selective inhibitors.
• The discovery of pyrazolylbenzamide leads provided a series with
more attractive physical properties for optimisation of vivo activity.
• The design of pyrazolylbenzamide with the appropriate balance of
pKa, lipophilicity and polarity lead to potent FGFR inhibition in vivo and
the identification of AZD4547.
• AZD4547 is a potent, orally bioavailable inhibitor of FGFR tyrosine
kinases 1, 2 and 3.
• AZD4547 is selective versus a number of off-target kinases including
KDR and has favourable drug properties.
• Genetic dysregulation of FGFRs confers sensitivity to AZD4547 in
tumour cell lines and primary, ex-plant tumour models
• AZD4547 is currently in Phase I/II clinical trials

41. 42
LO Discovery Translational science
Innovation Centre China
Paul Gavine
Qunsheng Ji
Xinying Su
Katherine Ye
Lucy Yin
Jingchuan Zhang
Liang Xie
Min Shi
Jessie Xu
David Zhang
Qiuli Guo
Shirley Zhang
Maggie Wang
Acknowledgments
Alderley Park UK
Andy Thomas
Maria-Elena Theoclitou
David Buttar
Linette Ruston
Gail Wrigley
Mike Dennis
David Rudge
Tanya Coleman
Robin Smith
Paul Gavine
Teresa Klinowska
Lorraine Mooney
Neil Smith
Dawn Baker
Nigel Brooks
LG Discovery
Alderley Park UK
Andrew Leach
Richard Norman
Anne-Kathrin Schott
Jason Breed
Kevin Foote
Andrew Garner
Derek Ogg
Jonathon Orme
Jennifer Pink
Karen Roberts
Frances Wang
Lin Zhang
Ming Li
ShuQiong Fan
Kunji Liu
Zhengwei Dong
Guanshan Zhu
Lili Tang
Alderley Park
UK
Elaine Kilgour
Paul Smith

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43 Andy Thomas | 22 May 2012 R&D | Oncology iMed