Slide 1: GT-020 Phase 1 Clinical Trial: Results of First Cohort
Exhibit 99.1 GT-020 Phase 1 Clinical Trial: Results of First Cohort Release: March 31, 2014 NASDAQ: GALT Webcast: April 1, 2014 www.galectintherapeutics.com © 2014 Galectin Therapeutics inc.
Slide 2: Forward-Looking Statement
Forward-Looking Statement This presentation contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as “may,” “
Slide 3: Our Pipeline Of Galectin-3 Inhibitors
Our Pipeline Of Galectin-3 Inhibitors Clinical Focus Stage of Development Drug Indication Discovery Pre-clinical Phase 1 Phase 2 Phase 3 Fibrosis Report on first Fatty liver disease with GR-MD-02 advanced fibrosis cohort of Phase 1 Clinical Trial Lung fibrosis Kidney fibrosis Timely Reporting: Last
Slide 4: Summary of Findings
Summary of Findings • GR-MD-02 was safe and well tolerated at 2 mg/kg (80 mg/m 2) with no drug- related adverse events • Pharmacokinetics was consistent between individuals and after single and multiple doses; exposure was 40% of lowest dose used in NASH animal model; this was a therapeutic dose • K
Slide 5: All Chronic Liver Diseases Lead To Fibrosis
All Chronic Liver Diseases Lead To Fibrosis Example: Liver Fibrosis In Fatty Liver Disease (NASH) Stage 1 Stage 2 Stage 3 Stage 4 Liver biopsy Blue=fibrosis Pericellular/Central Portal/Central Bridging Fibrosis Cirrhosis (High Mag) Healthy Fatty Fibrosis Cirrhosis Only therapy for patients with Live
Slide 6: Galectin-3 is Expressed In Liver Macrophages And Is Markedly Increased In NASH
Galectin-3 is Expressed In Liver Macrophages And Is Markedly Increased In Human and Mouse NASH Immunohistochemistry for Gal-3 (brown pigment indicates gal-3) Normal Mouse Liver NASH Mouse Liver • Kupffer cells= liver resident macrophages • Portal macs=macrophages located in portal regions NASH Human
Slide 7: GR-MD-02 Has Therapeutic Effect On NASH With Fibrosis In Mouse Model
GR-MD-02, A Galectin-3 Inhibitor, Has Therapeutic Effect On NASH With Fibrosis In Mouse Model Improvement is linked to decreased tissue Galectin-3 Normal NASH:Control NASH:GR-MD-02 GR-MD-02 Effects H&E NAFLD Activity Score • Fat • Cell death • Inflammation Sirius Red Collagen (Fibrosis) Gal-3 Galect
Slide 8: GR-MD-02 Reduces Collagen Synthesis And Increases Collagen Degradation In Pre-Clinical Models
GR-MD-02 Is A Galectin-3 Inhibitor That Reduces Collagen Synthesis And Increases Collagen Degradation In Pre-Clinical Models Liver Fibrotic Tissue Homeostasis In the normal liver, collagen and matrix protein synthesis matches Normal degradation to provide appropriate amount of extracellular matrix.
Slide 9: GR-MD-02 Is Being Developed For NASH With Advanced Fibrosis
GR-MD-02 Is Being Developed For The Indication Of NASH With Advanced Fibrosis (Stage 3 and 4) Obesity/Insulin Resistance/Diabetes Steatosis (fatty liver) NASH (inflammation, cell death) Stage 1 2 3 Stage 4 Clinical Outcomes Fibrosis Cirrhosis Complications Transplant Death Early Disease Late Disease
Slide 10: Phase 1 Clinical Trial Of GR-MD-02 In NASH With Advanced Fibrosis: Report On Cohort 1
Phase 1 Clinical Trial Of GR-MD-02 In NASH With Advanced Fibrosis: Report On Cohort 1 Patient inclusion: Biopsy proven NASH with advanced fibrosis (stage 3) Design: Cohort has 8 patients (6 active, 2 placebo, blinded) Dose: Starting dose of 2 mg/kg lean body weight (equivalent to 80 mg/m 2 ); Infusi
Slide 11: Patient Characteristics & Safety
Patient Characteristics & Safety Patient Characteristics Patient Safety • 6 women and 2 men • There were no Serious Adverse Events • Ages 40-64 (mean=54) • There were no Treatment Emergent • Mean body mass index (BMI)=39 Adverse Events in patients receiving GR- (obese >30) MD-02 that were attributed
Slide 12: Pharmacokinetics: GR-MD-02 Blood Levels Were Consistent Between Individuals
Pharmacokinetics: GR-MD-02 Blood Levels Were Consistent Between Individuals And Not Significantly Different After Single Or Multiple Infusions Mean GR-MD-02 Plasma Concentration-Time First Infusion (week 1) Profiles of 6 Patients on Weeks 1 and 7 Cmax = 16.3 µg/mL T1/2 = 19.9 h AUC = 572.6 h*µg/mL V
Slide 13: Assessment Methods for Liver Fibrosis
Assessment Methods for Liver Fibrosis Liver Serum Hepatic venous pressure biopsy markers gradient (HVPG) WHVP FHVP • Potential serious complications • 1/50,000 th of liver Time (s) • High sampling variability • 41% discordance of 1 fibrosis Functional metabolic and stage in NASH* shunt tests (eg. He
Slide 14: Major Pathological Processes in NASH
Major Pathological Processes in NASH Steato-Hepatitis (NASH Activity) Fibrosis/Cirrhosis • Ballooning of liver cells (cell • Increase in collagen/matrix death/apoptosis) key hallmark • Disruption of architecture • Fat in liver cells (steatosis) • Liver cell nodules • Immune cell infiltration (inflam
Slide 15: Serum Biomarkers Of Fibrosis In NASH
Serum Biomarkers Of Fibrosis In NASH Composite Scores Individual Markers FibroTest™ (FibroSURE™) • Indirect biomarker of fibrosis Hyaluronic Acid • Age and gender, Alpha-2- • Matrix polysaccharide macroglobulin, Haptoglobin, • Direct marker Apolipoprotein A1, GGTP, Total • Correlates to fibrosis bil
Slide 16: FibroTest Scores Significantly Decreased In GR-MD-02 Treated Patients
FibroTest ™ (FibroSURE™) Scores Significantly Decreased In GR-MD-02 Treated Patients Equivalent to a 10% change on scale FibroTest ™ has been shown to: • Correlate with stage of fibrosis • Assess fibrosis regression **One patient on GR-MD-02 had scores < 0.08 which was highly • Assess fibrosis progr
Slide 17: ELF Score Tended To Decrease In GR-MD-02 Treated Patients
ELF Score Tended To Decrease In GR-MD-02 Treated Patients Equivalent to a 0.5 change on scale 11.5 Severe Fibrosis 10.1 9.8 Moderate Fibrosis 8.8 7.7 Mild/No ELF score has been shown to: Fibrosis • Correlate with stage of fibrosis • Assess progression (0.032 increase/yr in PBC) *Siemens Diagnostics
Slide 18: Hyaluronic Acid Levels Were Decreased In A Subset Of Patients On GR-MD-02
Hyaluronic Acid (HA) Levels Were Decreased In A Subset Of Patients On GR-MD-02 Animal Study Study Results • HA levels measured in NASH mice • 3 of 6 patients treated with GR-MD-02 had treated with GR-MD-02 significant reductions in HA • HA levels decreased at all three doses • No change in placebo p
Slide 19: Serum Biomarkers of NASH Inflammation and Injury
Serum Biomarkers of NASH Inflammation and Injury Inflammatory Cytokines Cellular Injury Key cytokines* Serum Transaminases • IL-6 • ALT and AST • Enzymes released from liver cells • IL-8 • 2/3 of NASH patients have normal • TNF- levels at any given time Exploratory** • Entire spectrum of disease can
Slide 20: Interleukin-8 Levels Were Significantly Reduced In GR-MD-02 Treated Patients
Interleukin-8 Levels Were Significantly Reduced In GR-MD-02 Treated Patients • Pro-inflammatory cytokine expressed in macrophages • Elevated serum levels in NASH • Study patients had elevated serum levels • GR-MD-02 treated patients had significant reduction when compared to placebo Study NAFLD** Ob
Slide 21: TNF-alpha Levels Were Significantly Reduced In GR-MD-02 Treated Patients
TNF- Levels Were Significantly Reduced In GR-MD-02 Treated Patients • Pro-Inflammatory cytokine and promotes lipid accumulation • Elevated serum levels in NASH • Study patients had elevated serum levels • GR-MD-02 treated patients had significant reduction when compared to placebo Study NAFLD** Obes
Slide 22: Interleukin-6 Levels Were Significantly Reduced In GR-MD-02 Treated Patients
Interleukin-6 Levels Were Significantly Reduced In GR-MD-02 Treated Patients • Pro-Inflammatory cytokine secreted by T cells and macrophages. • Increased serum levels in NASH • Levels not increased in patients • GR-MD-02 treated patients had significant reduction when compared to placebo Study NAFLD
Slide 23: Markedly Elevated ALT Levels Decreased With GR-MD-02 Treatment
Markedly Elevated Alanine Aminotransferase (ALT) Levels Decreased With GR-MD-02 Treatment • Typical for NASH patients, there was a broad range of baseline ALT levels • Those with ALT levels below 50 U/L had no change with therapy • Two patients with ALT above 100 U/L, both of whom received active dr
Slide 24: Cell Death Biomarker CK18 Was Reduced In Two Patients With Highest ALT Levels
Cell Death Biomarker CK18 Was Reduced In Two Patients With Highest ALT Levels • CK-18, a biomarker of cell death of hepatocytes, was markedly reduced in the two patients with ALT greater than 100 U/L ALT CK-18 (M65) © 2014 Galectin Therapeutics | NASDAQ:GALT 24
Slide 25: Fibrosis Biomarkers Were Reduced In The Two Patients With Highest ALT
Fibrosis Biomarkers Were Reduced In The Two Patients Receiving GR-MD-02 With Highest ALT* • FibroTest™ scores were markedly decreased in the high ALT patients after treatment with GR-MD-02 • Lumican, a matrix protein that is involved in fibrogenesis in the liver, was elevated in all patients, but wa
Slide 26: Patients With Low ALT Levels Had Improvement In Fibrosis Markers But Not Cell Death Markers
Patients With Low ALT Levels Receiving GR-MD-02 Had Improvement In Fibrosis Markers But Not Cell Death Markers ALT CK-18 (M65) FibroTest™ Lumican • The three GR-MD-02 treated patients with low ALT levels did not have changes in ALT • These three patients had lower CK-18 levels which did not decrease
Slide 27: GR-MD-02 Treatment Appears To Improve Both Major Pathological Processes In NASH
GR-MD-02 Treatment Appears To Improve Both Major Pathological Processes In NASH Steato-Hepatitis (NASH Activity) Fibrosis/Cirrhosis • Ballooning of liver cells (cell • Increase in collagen/matrix death/apoptosis) key hallmark • Disruption of architecture • Fat in liver cells (steatosis) • Liver cell
Slide 28: Patients Had A Normal Range Of Blood Galectin-3 Levels At Baseline And No Change With Treatment
Patients Had A Normal Range Of Blood Galectin-3 Levels At Baseline And No Change With Treatment Cohort Normal Range* Range** Gal-3 13.2 to 25.2 5.4 to 26.2 (ng/mL) *Baseline values **Range of values in a non- diseased population published by manufacturer (BG Medicine) Timing of gal-3 levels • Before
Slide 29: Blood and Tissue Levels Of Galectin-3 Are Not Correlated In Mouse NASH Model Nor Human NASH
Blood and Tissue Levels Of Galectin-3 Are Not Correlated In Mouse NASH Model Nor Human NASH Marked changes in expression of galectin-3 in liver macrophages are not reflected in changes in blood galectin-3 Liver Gal-3 Staining Liver Tissue Level Blood Level Normal NASH • No evidence for correlation b
Slide 30: Summary of Findings
Summary of Findings • GR-MD-02 was safe and well tolerated at 2 mg/kg (80 mg/m 2) with no drug- related adverse events • Pharmacokinetics was consistent between individuals and after single and multiple doses; exposure was 40% of lowest dose used in NASH animal model; this was a therapeutic dose • K
Slide 31: Next Steps: Continuation of Phase 1 Trial
Next Steps: Continuation of Phase 1 Trial • The dose of GR-MD-02 will be increased to 4 mg/kg (160 mg/m 2) in the second cohort of 8-10 patients • Eight clinical sites in the US are now active to facilitate rapid enrollment of cohort 2 • FibroScan™, a FDA-approved ultrasonic measure of liver tissue