Galectin Therapeutics Inc. · NASDAQ:GALT
Galectin Therapeutics — NASH Summit 2018
30 slides from Galectin Therapeutics's conference presentation, Apr 25, 2018
Slide 1: Clinical Trials & Endpoints in NASH Cirrhosis
Clinical Trials & Endpoints in NASH Cirrhosis April 25, 2018 Peter G. Traber, MD CEO & CMO, Galectin Therapeutics 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 2: Chronic Liver Disease, Cirrhosis and its Progression
Chronic Liver Disease, Cirrhosis and its Progression Compensated Decompensated Chronic Cirrhosis Cirrhosis Liver ↑ Liver Fibrosis Disease • NASH • Viral Hepatitis • Alcohol • Variceal Bleeding • Other • Ascites • Encephalopathy • Jaundice/Liver Failure • Hepatocellular Carcinoma 2018 Galectin Galect
Slide 3: Survival Between Compensated and Decompensated Cirrhosis
Survival Between Compensated and Decompensated Cirrhosis Percent Alive Months D’Aminco et. Al., J Hepatol 2006;44:217 (Graphic borrowed from Dr. Guadalupe Garcia-Tso) 2018 Galectin GalectinTherapeutics Therapeutics||NASDAQ: NASDAQ:GALT GALT For more information, see galectintherapeutics.com
Slide 4: Portal Hypertension is the Main Driver of Decompensation
Portal Hypertension is the Main Driver of Decompensation Portal Pressure Compensated Decompensated Cirrhosis Cirrhosis D’Aminco et. Al., J Hepatol 2006;44:217 2018 Galectin GalectinTherapeutics Therapeutics||NASDAQ: NASDAQ:GALT GALT For more information, see galectintherapeutics.com
Slide 5: Portal Hypertension is Initiated by Increased Intrahepatic Resistance
Portal Hypertension is Initiated by Increased Intrahepatic Resistance Increased Resistance Portal Hypertension 5 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 6: Multiple Contributors to Increased Intrahepatic Blood Flow Resistance in Cirrhosis
Multiple Contributors to Increased Intrahepatic Blood Flow Resistance in Cirrhosis Normal Liver Acinar Unit Distorted Architecture in Cirrhosis Structural Components Scar tissue Stellate cells Regenerative nodules Neoangiogenesis Micro thrombosis Non-Structural Components Nitric Oxide Endothelin Eic
Slide 7: Cirrhosis Complications Center Around Increased Portal Vein Blood Pressure
Cirrhosis Complications Center Around Increased Portal Vein Blood Pressure Encephalopathy Increased Resistance Shunting Hepatic Insufficiency Portal Hypertension Splanchnic vasodilatation Increased Flow Effective Increased Hypovolemia Cardiac Output Neurohormonal Na/H2O Activation Retention Ascites
Slide 8: Critical Importance of Esophageal Varices in Cirrhosis
Critical Importance of Esophageal Varices in Cirrhosis An important goal of treatment of patients with compensated cirrhosis without esophageal varices is to prevent progression to varices and complications Esophagus: No Varices Esophageal Varices Bleeding Esophageal Varices 2018 Galectin GalectinTh
Slide 9: In Compensated HCV Cirrhosis, Varices Linked to Greater Decompensation and Death
In Compensated HCV Cirrhosis, the Presence of Varices is Associated with Greater Probabilities of Decompensation and Death Cirrhosis Decompensation Liver-Related Death Bruno et. al., Am J Gastro 2009;104:1147 (Graphic borrowed from Dr. Guadalupe Garcia-Tso) 2018 Galectin GalectinTherapeutics Therape
Slide 10: In Compensated HCV Cirrhosis, Varices Prior to Treatment Determine Decompensation
In Compensated HCV Cirrhosis, the Presence of Varices Prior to HCV Treatment Determines Decompensation Post-SVR No Varices Varices DiMarco et. al., Gastroenterology 2016;151:131 (Graphic borrowed from Dr. Guadalupe Garcia-Tso) 2018 Galectin GalectinTherapeutics Therapeutics||NASDAQ: NASDAQ:GALT GALT
Slide 11: Targeting NASH Cirrhosis
Targeting NASH Cirrhosis Compensated Cirrhosis Decompensated Cirrhosis NASH: Stage 1 Stage 2 Stage 3 and 4 Cell Death Fatty Liver Inflammation No Varices Varices Develop Bleeding, Ascites, Encephalopathy Fibrosis ≥6 >10 Portal Pressure (mmHg) >12 Estimated US Prevalence 80 - 100M 24 - 30M 1.5-2.5M 1
Slide 12: Potential Clinical Trial Endpoints in NASH Cirrhosis
Potential Clinical Trial Endpoints in NASH Cirrhosis Feels, functions, and survival Patient Outcomes Decompensation events: bleeding varices, ascites, hepatic encephalopathy, transplant, death HCC; Patient reported quality of life (?) Hepatic Venous Pressure Gradient Portal Pressure Crossing thresho
Slide 13: Liver Function Should be Area of Future Focus
Liver Function Should be Area of Future Focus, as in Other Organ Failure Feels, functions, and survival Patient Outcomes Decompensation events: bleeding varices, ascites, hepatic encephalopathy, transplant, death HCC; Patient reported quality of life (?) Metabolism: 13C methacetin breath test Liver
Slide 14: Rationale for Galectin-3 Inhibition in NASH
Rationale for Galectin-3 Inhibition in NASH Ø 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 Ø Gal-3 null mice are resistant to NASH and fibrosis Gal-3 Ø Gal-3 involved in multiple pathophysio
Slide 15: 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 16: Study Endpoints & Assessment Methods
Study Endpoints & Assessment Methods Ø Primary Endpoint (baseline and week 54) § Change in Hepatic Venous Pressure Gradient (HVPG) • Standardized Procedure and Central Blinded Reading Ø Secondary Endpoints (baseline and week 54) § Change in Liver Histology • NAFLD Activity Score and Fibrosis Staging
Slide 17: 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 18: 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) 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.
Slide 19: 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 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 20: 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 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 21: 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) * * Traber, P.G. and E. Zomer, Therapy of experimental NASH and fibrosis with galectin inhibitors. PLoS. One, 2013. 8(12): p. e83481. 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectinther
Slide 22: 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) 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 23: Changes in Liver Histology in Total Patient Population
Changes in Liver Histology in Total Patient Population Ø Trend towards improvement in NAS that did not reach significance Ø No differences in steatosis across the treatment groups Ø Statistically significant difference between GR2 and placebo for inflammation scores in the patients without baseline
Slide 24: 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. 2018 Galecti
Slide 25: Fewer Patients in GR Groups Developed New Varices
Fewer Patients in GR Groups Developed New Varices Chi Square Analysis 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 26: 13C-Methacetin Breath Test for Quantitative Liver Function Analysis
13C-Methacetin Breath Test for Quantitative Liver Function Analysis 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 27: 13C-Methacetin Breath Test in Patients Without Baseline Varices
13C-Methacetin Breath Test in Patients Without Baseline Varices Ø Evaluated at baseline and end of study (54 weeks) Ø Measure was either improvement or worsening of methacetin breath test (MBT) Ø Statistically significant difference between GR2 and placebo (PBO) Ø No difference between GR8 and place
Slide 28: Conclusions From NASH-CX Clinical Trial
Conclusions From NASH-CX Clinical Trial Ø Δ HVPG associated with GR treatment was not significant in total patient population, but was statistically significant in the pre-specified group of mild portal hypertension Ø In patients without varices at baseline, there was a statistically significant dif
Slide 29: Possible Registration Endpoints in Compensated NASH Cirrhosis
Possible Registration Endpoints in Compensated NASH Cirrhosis Non-Cirrhotic Compensated Decompensated NASH NASH Cirrhosis NASH Cirrhosis No Varices Varices Reduced progression to complications At least 1 stage reduction in fibrosis (NASH-CRN system) (reversal of cirrhosis) Reduced progression to var
Slide 30: Acknowledgements
Acknowledgements We extend our thanks to the patients, their families and all participating investigators This study was funded by Galectin Therapeutics, Inc. 2018 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com