Slide 1: Phase 1 Clinical Trial Results Of GR-MD-02 In NASH With Advanced Fibrosis
Exhibit 99.1 AASLD Abstract No. 57 Phase 1 Clinical Trial Results Of GR-MD-02, A Galectin-3 Inhibitor, In Patients Having Non-Alcoholic Steatohepatitis (NASH) With Advanced Fibrosis Stephen A. Harrison 1, Naga P. Chalasani 2, Eric Lawitz3, Smitha Marri 2, Mazen Noureddin4, Arun J. Sanyal 5, Thomas D
Slide 2: Author Disclosures
Author Disclosures • Stephen A. Harrison – Advisory Committees or Review Panels; Merck, Nimbus Discovery, NGM Bio, Fibrogen. Grant/Research Support: Merck, Genentech; Speaking and Teaching: Merck, Gilead, Janssen, AbbVie. • Naga P. Chalasani – Consulting: Salix, AbbVie, Lilly, Boerhinger-Ingelham, A
Slide 3: Presenter Disclosure Slide
Presenter Disclosure Slide “The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, Department of Defense or th
Slide 4: Background
Background • Advanced liver fibrosis and cirrhosis are unmet medical needs • NASH is the most common liver disease in the US and a growing cause of cirrhosis requiring liver transplantation • Galectin-3 is a protein that binds to terminal galactose residues on glycoproteins and is highly expressed i
Slide 5: Pre-Clinical: GR-MD-02 Has Therapeutic Effect On NASH With Fibrosis In Mouse Model
Pre-Clinical: GR-MD-02 Has Therapeutic Effect On NASH With Fibrosis In Mouse Model* Normal NASH:Control NASH:GR-MD-02 GR-MD-02 Effects H&E NAFLD Activity Score • Fat • Cell death • Inflammation Pico Sirius Red Collagen (Fibrosis) Galectin-3 Galectin-3 Protein *Traber PG and Zomer E. Therapy of Exper
Slide 6: Pre-Clinical: GR-MD-02 Reversed Cirrhosis And Improved Portal Hypertension In Rat Model
Pre-Clinical: GR-MD-02 Reversed Cirrhosis And Improved Portal Hypertension In Thioacetamide-Treated Rat Model* Vehicle-Treated Collagen Portal Pressure GR-MD-02-Treated (90 mg/kg, 1/W x 4) N=10 N=10 N=10 N=10 N=10 *Traber PG, Chou H, Zomer E, Hong F, Klyosov A Fiel M-I, Friedman, SL. Therapy of Regr
Slide 7: Multi-Center Maximum Tolerated Multiple Dose Escalation Phase 1 Clinical Trial
A Multi-Center, Partially Blinded, Maximum Tolerated Multiple Dose Escalation, Phase 1 Clinical Trial to Evaluate the Safety of GR-MD-02 in Subjects with Non-Alcoholic Steatohepatitis (NASH) with Advanced Hepatic Fibrosis • Overall Objective: • Evaluate safety and pharmacokinetics of GR-MD-02 to pro
Slide 8: Methods: Three Cohort Design Of Phase 1 Clinical Trial
Methods: Three Cohort Design Of Phase 1 Clinical Trial • Subjects: Biopsy proven NASH with Brunt Stage 3 fibrosis • Design: • Blinded, placebo controlled, sequential dose escalation • Three cohorts: 2, 4, and 8 mg/kg lean body weight administered by IV infusion over one hour • Primary Endpoints: Saf
Slide 9: Results: Patient Characteristics
Results: Patient Characteristics Cohort 1 Cohort 2 Cohort 3* (2 mg/kg) (4 mg/kg) (8 mg/kg) Enrolled 8 10 13 Completed 8 9 9 Pending Completion -- -- 4 by end of December Completed Patients Age Range (Mean) 40-64 (54) 34-69 (51.5) 44-69 (61) Sex (M/F) 2/6 6/4 5/4 BMI (Mean) 39 39.6 33.2 BMI 30 8/8 9/
Slide 10: Results: Safety Data On Completed Patients
Results: Safety Data On Completed Patients Cohort 1 Cohort 2 Cohort 3 (2 mg/kg) (4 mg/kg) (8 mg/kg) Active Placebo Active Placebo Active Placebo Completed protocol 6 2 7 2 6 3 Serious Adverse Events 0 0 0 0 0 0 TEAE’s probably related 0 0 0 0 0 0 TEAE’s possibly related 0 2 2 0 0 1 • Therapy Emergen
Slide 11: Results: Mean GR-MD-02 Plasma Concentration-Time Profiles
Results: Mean GR-MD-02 Plasma Concentration-Time Profiles After First And Fourth Doses In All Three Cohorts • Proportional increase in drug coverage (AUC) for 2 mg/kg, 4 mg/kg, and first dose of 8 mg/kg • Increase in AUC after four doses of 8 mg/kg indicates a saturable compartment model Cmax T1/2 A
Slide 12: Pharmacokinetics Indicates 8 mg/kg Dose Is Within Upper Range Of Targeted Therapeutic Window
Pharmacokinetics Indicates 8 mg/kg dose Is Within The Upper Range Of The Targeted Therapeutic Window • The best therapeutic dose in mouse NASH was between 10 and 30 mg/kg • Relationship between AUC and dose shows mouse and human equivalency Target Therapeutic Window AUC of Human 8 mg/kg dose AUC of
Slide 13: Results: Exploratory Serum Biomarkers
Results: Exploratory Serum Biomarkers • There are no validated serum biomarkers for evaluation of potential therapeutic changes over time in NASH or fibrosis • A panel of serum tests were evaluated to explore potential biomarkers for use in future studies • Most of the putative biomarkers showed hig
Slide 14: Results: FibroTest (FibroSure) Scores
Results: FibroTest ® (FibroSure®) Scores ns ns ns p < 0.05 p < 0.01 Placebo GR GR GR GR GR 2 nd dose 4 th dose 4 th dose 4 th dose 4 th dose + 3 da + 14 da + 14 da + 3 da Cohort 3** Cohort 1*** Cohort 2*** * Placebo values were combined after showing that there was no difference between different ti
Slide 15: Results: Alpha-2 Macroglobulin Serum Levels
Results: Alpha-2 Macroglobulin Serum Levels ns ns p < 0.05 p < 0.005 p < 0.001 Placebo GR GR GR GR GR 2 nd dose 4 th dose 4 th dose 4 th dose 4 th dose + 3 da + 14 da + 14 da + 3 da Cohort 3** Cohort 1*** Cohort 2*** * Placebo values were combined after showing that there was no difference between d
Slide 16: Summary
Summary • Administration of 2, 4, and 8 mg/kg lean body weight of GR-MD-02 intravenously for four doses over 6 weeks was safe and well tolerated in NASH patients with advanced fibrosis • PK analysis demonstrated 8 mg/kg achieves targeted therapeutic dosing range derived from animal studies • Analysi
Slide 17: Phase 2 Clinical Trial Plans
Phase 2 Clinical Trial Plans • A Phase 2 clinical trial is planned based on: • Pre-clinical efficacy • Phase 1 safety and tolerability • Phase 1 PK and animal model/human dose equivalency • Phase 1 evidence of pharmacodynamic effect at high dose • The company has informed the study investigators tha