Galectin Therapeutics Inc. · NASDAQ:GALT
Galectin Therapeutics — Technical Presentation (April 2018)
19 slides from Galectin Therapeutics's technical presentation, Apr 12, 2018
Slide 1: The NASH-CX Trial: GR-MD-02 in NASH cirrhosis and portal hypertension
A multicenter, randomized, double-blind, placebo-controlled trial of Galectin-3 inhibitor (GR-MD-02) for one year in patients with NASH cirrhosis and portal hypertension The NASH-CX Trial 1Naga Chalasani, 2Guadalupe Garcia-Tsao, 3Zachary Goodman, 4Eric Lawitz, 5Manal Abdelmalek, 6Mary Rinella, 7Mich
Slide 2: Rationale for Galectin-3 Inhibition in NASH
Rationale for Galectin-3 Inhibition in NASH ➢ Gal-3 is a lectin protein that binds to galactose residues on glycoproteins and is increased in NASH and liver Stellate Macrophage fibrosis/cirrhosis Cell ➢ Gal-3 null mice are resistant to NASH and fibrosis Gal-3 ➢ Gal-3 involved in multiple pathophysio
Slide 3: NASH-CX Clinical Trial Design
NASH-CX Clinical Trial Design AIM: Evaluate Safety and Efficacy of GR-MD-02 in Compensated NASH Cirrhosis NASH cirrhosis (biopsy) No decompensating event Major Inclusion Criteria HVPG ≥ 6 mmHg No or small varices Week 1 Week 54 n = 54 Placebo (PLB) n = 54 GR-MD-02 2 mg/kg (GR2) n = 54 GR-MD-02 8 mg/
Slide 4: Study Endpoints & Assessment Methods
Study Endpoints & Assessment Methods ➢ Primary Endpoint ▪ Change in Hepatic Venous Pressure Gradient (HVPG) • Baseline and Week 54 • Standardized Procedure and Central Blinded Reading ➢ Secondary Endpoints ▪ Change in Liver Histology • NAFLD Activity Score and Fibrosis Staging • Quantitative Morphom
Slide 5: Study Disposition (36 US Sites)
Study Disposition (36 US Sites) N = 290 Patients Screened N = 128 Screening Failures N = 162 No Varices = 81 Patients Randomized (1 withdrew before 1st dose) N = 54 N = 53 N = 54 Placebo (PLB) 2 mg/kg GR-MD-02 (GR2) 8 mg/kg GR-MD-02 (GR8) Discontinued Treatment = 3 Discontinued Treatment = 1 Discont
Slide 6: Study Demographics & Baseline Assessments
Study Demographics & Baseline Assessments Total Placebo GR2 GR8 (n=162) (n=54) (n=54) (n=54) Age, years; median (IQR) 59 (52, 65) 59 (53, 64) 60 (53, 65) 58 (51, 63) Female, n (%) 113 (70) 36 (67) 34 (63) 43 (79) Non-Hispanic White, n (%) 132 (81) 46 (85) 46 (85) 40 (74) BMI, kg/m2; median (IQR) 34
Slide 7: Baseline HVPG (mmHg) in Patient Groups
Baseline HVPG (mmHg) in Patient Groups Total Placebo GR2 GR8 Mean ± SD (n) Mean ± SD (n) Mean ± SD (n) Mean ± SD (n) Full Analysis Set 12.2 ± 4.2 (162) 11.6 ± 4.0 (54) 12.4 ± 4.3 (54) 12.7 ± 4.2 (54) CSPH Sub-group 14.3 ± 3.4 (108) 14 ± 3.1 (33) 14.2 ± 3.9 (37) 14.8 ± 3.1 (38) MPH Sub-Group 7.9 ± 1.
Slide 8: HVPG Primary Endpoint (Pre-Specified Analyses)
HVPG Primary Endpoint (Pre-Specified Analyses) Total Patient Population Mild Portal Hypertension mean ± SEM mean ± SEM ITT with LOCF (last observation carried forward); ANOVA with LSD (least squared difference)
Slide 9: No Esophageal Varices at Baseline (Post Hoc Analysis)
No Esophageal Varices at Baseline (Post Hoc Analysis) 50% of patients (81) did not have varices at baseline mean ± SEM ITT with LOCF; ANOVA with LSD
Slide 10: Responder Analysis (Post Hoc Analysis)
Responder Analysis (Post Hoc Analysis) Percentage of Patients Who Had a Clinically Relevant Reduction in HVPG With: • ≥ 2 mmHg Decrease From Baseline AND • ≥ 20% Decrease From Baseline Chi Square Analysis
Slide 11: PK-PD Correlation Between Human and Mouse Data
PK-PD Correlation Between Human and Mouse Data AUC of patients in NASH- CX (µg*hr./mL) 1Traber, P.G. and E. Zomer, Therapy of experimental NASH and fibrosis with galectin inhibitors. PLoS. One, 2013. 8(12): p. e83481.
Slide 12: Change in HVPG Using PK Range Groups for GR8
Change in HVPG Using PK Range Groups for GR8 mean ± SEM ITT; ANOVA with LSD; AUC=area under concentration curve (µg*hr./mL)
Slide 13: Changes in Liver Histology in Total Patient Population
Changes in Liver Histology in Total Patient Population ➢ Trend towards improvement in NAS that did not reach significance ➢ No differences in steatosis across the treatment groups ➢ Statistically significant difference between GR2 and placebo for inflammation scores in the patients without baseline
Slide 14: Correlation of Liver Biopsy Findings in HVPG Responders
Correlation of Liver Biopsy Findings in HVPG Responders Total Patient Population GR21 GR81 Hepatocyte Ballooning 0.04 0.05 NAFLD Activity Score 0.19 0.28 Ishak Stage 0.20 0.59 1p value compared to placebo Ordinal logistic regression analysis was used to compare groups. ITT analysis set.
Slide 15: Fewer Patients in GR Groups Developed New Varices
Fewer Patients in GR Groups Developed New Varices Chi Square Analysis
Slide 16: Development of Cirrhosis Complications
Development of Cirrhosis Complications1 Total PLB GR2 GR8 FAS Population n=161 n=54 n=53 n=54 • Complications – n(%) 21 (13) 9 (17) 5 (9) 7 (13) No-Varices Population n=81 n=33 n=25 n=23 • Complications – n(%) 12 (15) 7 (21) 3 (12) 2 (9) MPH Population n=53 n=21 n=16 n=16 • Complications – n(%) 4 (8
Slide 17: Adverse Events
Adverse Events Total PLB GR2 GR8 (n=161) (n=54) (n=53) (n=54) Treatment Emergent (TE) AEs 1323 431 509 383 Patients with at least ≥ grade 3 AE (%) 33 (20.5) 11 (20.4) 11 (20.8) 11 (20.4) Patients with at least 1 TE SAE1 (total) 25 (34) 8 (10) 5 (10) 12 (14) Study drug discontinued due to AE 3 0 0 32
Slide 18: Conclusions
Conclusions ➢ Change in HVPG associated with GR treatment was not significant in total patient population, but statistically significant in the pre-specified group of mild portal hypertension ➢ In patients without varices at baseline, there was a statistically significant difference in the GR2 group
Slide 19: Acknowledgements
Acknowledgements We extend our thanks to the patients, their families and all participating investigators This study was funded by Galectin Therapeutics, Inc.
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