Methods: The phase 1 trial was designed as a multi-center, partially blinded CT99021 mw (patients, PI and staff), maximum tolerated

multiple dose escalation study in patients with biopsy proven NASH having stage 3 fibrosis. In the first cohort, 8 patients were randomized to receive 4 doses of either placebo (2 patients) or 2 mg/kg lean body weight (lbw) of GR-MD-02 (6 patients) by intravenous infusion on days 0, 28, 35 and 42. Drug levels were measured following the first and fourth doses. Serum biomarkers associated with fibrosis (including FibroTest® and the Enhanced Liver Fibrosis (ELF) score), with inflammation (including IL-6, TNFα and IL8), serum levels of aminotransferases, and GW-572016 research buy keratin 18 (K-18, also known as CK-18) were assessed at day -1 and day 56. Results: GR-MD 02 was safe and well tolerated following 4 doses of 2 mg/kg lbw with no treatment-associated adverse events. The pharmacokinet-ics were consistent between individuals and after single and multiple doses with no drug accumulation. FibroTest® scores were significantly reduced in GR-MD-02 treated patients (-27% ± 5.8 (SEM)) compared to placebo patients (3.5% ± 20.5, p=0.04, α<0.1). Although there was a tendency towards reduction in ELF scores in treated patients

(-3.8% ± 1.2) compared to placebo (-2% ± 2), the difference did not reach significance (p=0.2, α<0.1). Patients treated with GR-MD-02 also had significant reductions in serum biomarkers associated with inflammation when compared to patients treated with placebo, including IL-6 (-16% ± 4.7 vs. 6.5% ± 4.5, p=0.02, α<0.1), TNFα (-16% ± 6.9 vs. 20% ± 30, p=0.06, α<0.1), and IL-8 (-25.5% ± Thiamine-diphosphate kinase 3.6 vs.

-3.5% ± 12.5, p=0.02, α<0.1). Additionally, patients with greater evidence of liver cell injury, as indicated by elevated serum aminotransferase levels, had a marked decrease in serum K-18. Galectin-3 blood levels, which do not correlate with tissue levels in animal models of NASH, were not changed with treatment. Conclusions: This first human study of the galectin-3 inhibitor GR-MD-02 achieved its primary safety endpoint at a dose of 2 mg/kg. Additionally, this initial dose showed improvement in serum biomarkers of fibrosis and inflammation suggesting a potential beneficial disease effect. The clinical trial is ongoing using a dose of 4 mg/kg of GR-MD-02, which will be followed by an 8 mg/kg dose cohort. Disclosures: Stephen A. Harrison – Advisory Committees or Review Panels: Merck, Nimbus Discovery; Grant/Research Support: Merck, Genentech; Speaking and Teaching: Merck, Vertex Naga P.