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300
Platelet Count (x109/L)
9
4 300
PRECLINICAL RESULTS 250
250
3 200
200
150
In Vitro Bone Marrow Proliferation 2 150
100
100
Figure 1a. In Vitro Erythroid Proliferation Figure 1b. In Vitro Myeloid Proliferation 1
50
In vitro Erythroid Proliferation 50
70 100 0 0 0
70 90 1 3 5 7 9 11 13 15 1 3 5 7 9 11 13 15
60
1 3 5 7 9 11 13 15
80
Colony-Forming Units
Colony-Forming Units
70
50 60
40
Placebo 0.5 µg/kg 1.5 µg/kg 5 µg/kg 7.5 µg/kg
40 50
30
30 40
20 30 Neutrophil and platelet counts did not change significantly after a single dose of PEG-rIL-29
20
20 at any dose level tested. Neutrophils (Figure 3a) and platelets (Figure 3b) were enumerated by standard
10 10
10
hematologic methods at several timepoints following single subcutaneous doses (SC) of PEG-rIL-29. Points
0 0
represent median cell counts for each dose level tested.
0
Control 1 ng/mL 10 ng/mL
Control 100 ng/mL
1 ng/mL 10 ng/mL Control
100 ng/mL 1 ng/mL 10 ng/mL 100 ng/mL
Concentration Concentration Concentration
PEG-rIL-29 did not inhibit in vitro proliferation of bone marrow precursor cells. Figure 4. Median PEG-rIL-29 Concentration Figure 5. Median B2M Concentration
Bone marrow cells obtained from human bone marrow aspirate were stimulated with PEG-rIL-29, 10
PEG-IFN-α2a, or PEG-IFN-α2b. Subsequently, erythroid colonies (Figure 1a) and myeloid colonies 3.5
(Figure 1b) were enumerated. Points represent average colony counts and error bars represent
one standard deviation. 3
400
Serum B2M (µg/mL)
2.5
PEG-rIL-29 (ng/mL)
350
Platelet Count (x109/L)
0 24 48 72 96
1 120 3 144 5168 7 1 9 3 11 5 137 915 11 13 15
Time (Hrs) Study Day
10 Study Day
Peak PEG-rIL-29 serum concentrations were Evaluated PEG-rIL-29 dose levels were
within concentration levels tested in vitro. pharmacologically active. Serum concentrations
Serum concentrations of PEG-rIL-29 were quantified by of B2M, a biomarker of PEG-rIL-29 pharmacological
1 a validated ELISA at several timepoints following single activity, were measured by a validated ELISA at
Control 5 ng/mL 50 ng/mL 500 ng/mL 5000 ng/mL SC doses of PEG-rIL-29. Points represent median various timepoints following single SC doses of
measured PEG-rIL-29 concentrations for each dose level PEG-rIL-29. Points represent median measured
Concentration tested. The assay limit of detection was 0.25 ng/mL. B2M concentrations for each dose level tested.
PEG-rIL-29 did not induce the in vitro release of IL-6 by PBMCs. PBMCs were
enriched from 10 healthy donors and stimulated with PEG-rIL-29 or PEG-IFN-α2a. Subsequently, the
concentration of IL-6 released into the cell culture medium was quantified by immunoassay. Points
represent geometric means and error bars represent one standard error of the mean. CONCLUSIONS
European Association for the Study of the Liver (EASL), 43rd Annual Meeting, Milan, Italy, April 2008