novimmune acr2015_anti-tlr4 translational and phase i_final

1
Part I: ex vivo LPS challenges were performed Part II: 3 subgroups of HV received an in vivo LPS challenge immediately, 22 or 40 days after NI-0101 infusion CD14 MD2 Ligand TLR4 MD2 TLR4 MD2 CD14 MyD88 X TRIFF cFb only cFb-IC cFb-IC + NI-0101 cFb-IC + Isotype cFb-IC + NI-0101 D265A cFb-IC + Isotype D265A 0 1000 2000 3000 4000 TNF (pg/mL) *** ** Cells alone RASF RASF + NI-0101 RASF + Isotype 0 5000 10000 15000 IL6 (pg/mL) *** *** ** NR R 0 20 500 1000 1500 2000 2500 ACPA (IU/mL) NR R 0.0 0.5 1.0 1.5 2.0 2.5 3.0 cFb-IC (OD 450 nm) NR R 0.0 0.5 1.0 1.5 2.0 2.5 3.0 S100A8/A9 ( g/mL) NR R 0 50 100 150 200 250 HMGB1 (ng/mL) *** * NR R -5 0 5 10 15 20 25 30 normalized delta OD NR R -2 0 2 4 6 8 10 12 14 16 normalized delta OD NR R -5 0 5 10 15 normalized delta OD NR R -5 0 5 10 15 20 100 200 normalized delta OD *** * * b 0.00 0.01 0.10 1.00 10.00 100.00 1000.00 0 20 40 60 80 100 120 Thousands (ng/mL) * : Anti-citrullinated protein antibodies

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Page 1: Novimmune ACR2015_anti-TLR4 translational and phase I_final

Adobe Garamond PRO (28pt).

• Part I: ex vivo LPS challenges were performed

• Part II: 3 subgroups of HV received an in vivo LPS

challenge immediately, 22 or 40 days after NI-0101 infusion

CD14

MD2

Ligand TLR4

MD2

TLR4

MD2

CD14

MyD88 X TRIFF

cF

b o

nly

cF

b-I

C

cF

b-I

C +

NI-

0101

cF

b-I

C +

Iso

typ

e

cF

b-I

C +

NI-

0101 D

265A

cF

b-I

C +

Iso

typ

e D

265A

0

1 0 0 0

2 0 0 0

3 0 0 0

4 0 0 0

TN

F

(p

g/m

L)

* * * * *

Cells a

lon

e

RA

SF

RA

SF

+ N

I-0101

RA

SF

+ Iso

typ

e

0

5 0 0 0

1 0 0 0 0

1 5 0 0 0

IL6

(p

g/m

L)

* * * * * * * *

NR R

0

2 0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

2 5 0 0

AC

PA

(IU

/mL

)

NR R

0 .0

0 .5

1 .0

1 .5

2 .0

2 .5

3 .0

cF

b-I

C

(OD

45

0 n

m)

NR R

0 .0

0 .5

1 .0

1 .5

2 .0

2 .5

3 .0

S1

00

A8

/A9

(

g/m

L)

NR R

0

5 0

1 0 0

1 5 0

2 0 0

2 5 0

HM

GB

1 (

ng

/mL

)

* * * *

NR R

-5

0

5

1 0

1 5

2 0

2 5

3 0

no

rma

liz

ed

de

lta

OD

NR R

-2

0

2

4

6

8

1 0

1 2

1 4

1 6

no

rma

liz

ed

de

lta

OD

NR R

-5

0

5

1 0

1 5

no

rma

liz

ed

de

lta

OD

NR R

-5

0

5

1 0

1 5

2 0

1 0 0

2 0 0

no

rma

liz

ed

de

lta

OD

* * * * *

b

0.00

0.01

0.10

1.00

10.00

100.00

1000.00

0 20 40 60 80 100 120

Th

ou

sa

nd

s (

ng

/mL

)

*: Anti-citrullinated protein antibodies