Slide 1: Galectin Therapeutics, Inc. Galectin Sciences, LLC
Galectin Therapeutics, Inc. Galectin Sciences, LLC
Slide 2: Forward Looking Statements
FORWARD LOOKING STATEMENTS 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: Galectin-3 CRD Druggability Is Poor
Galectin-3 CRD Druggability Is Poor Druggability evaluates suitability of the binding site for small molecules under the Lipinski's Rule of 5 [Druggable=1 / Undruggable=0]. Correlates with binding site hydrophobicity and curvature (Cheng, Nat. Comp. Biol. 2007). Galectin-3 Carbohydrate Receptor Doma
Slide 4: Commercial Positioning: Targeting Galectin-3 Inhibition for Unmet Medical Need
Commercial Positioning: Targeting Galectin-3 Inhibition as Therapeutic for Unmet Medical Need • Targeting pathologies with elevated tissue Gal-3 and fatty liver disease1 Organ • Lead pathology is liver fibrosis Fibrosis / • Other fibrotic diseases with elevated Gal-3 e.g. cardiovascular, kidney fail
Slide 5: Galectin Therapeutics Pharmaceutical Initial Development Plan
Galectin Therapeutics Pharmaceutical Initial Development Plan Optimize initial chemical processing of active poly-galactoside (GR-MD- 02) to enhance therapeutic effects in Liver Fibrosis where Gal-3 plays an important role in disease progression Establish discovery program for new anti-galectin m
Slide 6: Liver Fibrosis - Galectin-3 effects macrophages and stellate cells
Liver Fibrosis - Galectin-3 effects macrophages and stellate cells Copyright 2019 Galectin Sciences, LLC Page 6
Slide 7: Optimized Process by Evaluating Synthetic Oligo-galactosides Chain Structures
Optimized Process by Evaluating the Effect of Synthetic Oligo-galactosides* Chain Structures in Galectin-3 Binding Kd * In collaboration with Prof. Geert-Jan Boons, UGA Copyright 2019 Galectin Sciences, LLC Page 7
Slide 8: Therapy of experimental NASH and fibrosis with galectin inhibitors
Therapy of experimental NASH and fibrosis with galectin inhibitors model2 Study compared two Study compared two leading poly-galactose leading poly-galactose compositions In compositions for Murine NASH with Inhibition of Fibrosis Fibrosis on liver Gal-3 biomarker α-SMA 2 Traber PG, Zomer E.PLoS One
Slide 9: Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors
Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease3. Study Dose optimization for two leading poly-galactose compositions In Murine Hepatic venous pressure gradient (HVPG) Model with Advanced Cirrhosis Treatments Mean (SE) Group 1: V
Slide 10: NASH-CX Trial of GR-MD-02 in NASH cirrhosis
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 Trial4 4Naga Chalasani et al. EASL2018 Presentation Copyright 2019 Galectin Sciences, LLC Page 10
Slide 11: From Target to Market
From Target to Market Copyright 2019 Galectin Sciences, LLC Page 11
Slide 12: Phase III Targets Compensated Liver Cirrhosis without Varices
Phase III Targets Compensated Liver Cirrhosis without Varices5 Disease progression as indicated by Primary End point for Development of Varices in The Phase II Phase III • Development of Varices 5Naga Chalasani et al. EASL2018 Presentation Copyright 2019 Galectin Sciences, LLC Page 12
Slide 13: Galectin Sciences, LLC
Galectin Sciences, LLC Galectin Therapeutics (NASDAQ: GALT) ~80% SBH Sciences (private) ~ 20% In January 2014, Galectin Therapeutics and SBH Sciences formed GALECTIN SCIENCES, LLC, a collaborative venture to research and develop Galectin inhibitors for oral administration. Objectives: • Explore new
Slide 14: Screening Program
Screening Program: • First line: Computational In-silico libraries screening to identify chemicals effecting Ligand Interaction sites • Second line: Analysis of chemicals on Gal-3 interaction with synthetic & biological ligands • Di-Gal-FITC, Integrins, Gal-3 BP, insulin receptor, TGF-β1-Receptor1 e
Slide 15: Galectin-3 Multi-Faces – Computational In-silico Screening
Galectin-3 Multi-Faces – Computational In-silico Screening for Identification of Potential Sites Effecting Ligand Interaction Non-CRD Site CRD Site Copyright 2019 Galectin Sciences, LLC Page 15
Slide 16: In-vitro Gal-3 CRD Binding Screening Assays
In-vitro Gal-3 Carbohydrate Recognition Domain (CRD) Binding Screening Assays Fluorescent Polarization Assay: Uses a galactoside fluorescent probe that specifically binds to the Gal-3 CRD site. Copyright 2019 Galectin Sciences, LLC Page 16
Slide 17: In-vitro Gal-3 Binding to Functional Ligands
In-vitro Gal-3 Binding to Functional Ligands Functional ELISA assay measures the interaction of Gal-3 to Glycoproteins ligands like Integrin aVB6, Galectin-3 BP, Insulin Receptor, TGF-β1-R1, and others, reported to be essential in the pathology of a variety of diseases. Copyright 2019 Galectin Scien
Slide 18: Gal-3 Detection in Two Distinct Populations
Gal-3 Detection in Two Distinct Populations: Flow Cytometer Analysis of Stressed LX-2 Hepatic Stellate Cells peak #1 peak #2 Unstained FS alone Sample Treatment Gal3 stain (Y/N) mean FL1 % peak1 FL1 peak 1 % peak 2 FL1 peak 2 FS Alone Y 237,922 75.4% 69,537 24.6% 756,288 Copyright 2019 Galectin Scie
Slide 19: Galectin-3 Multi-Face Analysis by NMR-HSQC
Galectin-3 Multi-Face Analysis by NMR-HSQC (Heteronuclear Single Quantum Coherence) CRD domain Full Galectin-3 • Site Target 1:The CRD (the canonical Carbohydrate Recognition Domain) at the S- face has few NMR specific resonances that shift upon interaction with ligands. • Site Target 2:Published da
Slide 20: NMR Interaction Using 15N-enriched Gal-3 Protein
NMR Interaction Using 15N-enriched Gal-3 Protein* HSQC Spectra Overlays Convey Interacting Sites (black spot) 15N-protein + low 15N-protein + more polysaccharide polysaccharide * In collaboration with Prof. Kevin H. Mayo, Univ. of Minnesota Copyright 2019 Galectin Sciences, LLC 20
Slide 21: 15N-Gal-3 CRD + TD-139
15N-Gal-3 CRD (44 mM) + TD-139 (250 mM) Gal-3 + TD-139 (250 mM): Gal-3 + TD-139: Gave strong intensity HSQC Spectra overlays convey many for the interaction of specific aminoacids Interacting Sites (black spot) associated with the CRD site 0.30 0.25 0.20 ppm 0.15 0.10 0.05 0.00 120 135 150 165 18
Slide 22: 15N-Gal-3 FL + G226
15N-Gal-3 FL (20 mM) + G226 (~800 mM) 20 mM Kphos, pH 6.9, 5% DMSO Gal-3 + G226 (~800 mM): HSQC Gal-3 + G226: Gave Weak Intensity for Spectra overlays convey few the interaction of specific aminoacids Interacting Sites (black spot) associated with the CRD site 0.008 0.006 with G226 0.004 0.002 0.
Slide 23: In-silico Screening Phase: Computational Analysis on Libraries
In-silico Screening Phase: Computational Analysis on 12 Libraries Using 3D Model of Gal-3 2 platforms identified and evaluated • Platform I: Carbohydrate mimics compounds • Polyhydroxyls with heterocycle substitutions and derivatives • Commercial libraries – identified limited & mostly unavailable c
Slide 24: Platform I: Carbohydrate Mimics Attenuating Gal-3 Ligand Binding
Platform I: Carbohydrate Mimics Attenuating Gal-3 Ligand Binding through the CRD In an ELISA assay format inhibition of In a Fluorescent Polarization assay Gal-3 binding to integrin aVB3, SelenoCarbohydrate heterocycle Selenocarbohydrate heterocycle derivatives had 0.177 Kd. derivatives gave an IC50
Slide 25: Screening Platform II – Allosteric Compounds
Screening Platform II – Allosteric Compounds Attenuating Gal-3 ligand specificity through a none CRD site interaction AGS-229 – non-carbohydrate compound inhibits AGS-229 – In the Fluorescent Polarization Gal-3 binding to integrin aMB2 at IC50 (µg/mL) = 4.5. assay the IC50 (µg/mL) was > 50. The allo
Slide 26: Hematopoietic-Derived Galectin-3 Causes Cellular and Systemic Insulin Resistance
Hematopoietic-Derived Galectin-3 Causes Cellular and Systemic Insulin Resistance1 1 Pingping Li, et al., Nov 3, 2016, v 167 (4), p 973–984.e12 Copyright 2019 Galectin Sciences, LLC Page 26
Slide 27: Allosteric Compounds Attenuating Gal-3 Binding to Insulin Receptor and TGFb1-Receptor 1
Allosteric Compounds Attenuating Gal-3 Binding to Insulin Receptor and TGFb1-Receptor 1 Inhibition of Galectin-3 IC50 Inhibition of Galectin-3 IC50 Code Binding to Insulin Receptor 1 (ug/mL) binding to TGF-β1 Receptor-1 (ug/mL) AGS-164 4.3 5.1 AGS-155 3.7 4.2 Copyright 2019 Galectin Sciences, LLC Pa
Slide 28: Allosteric Compounds May Enhance Gal-3 Ligand Binding
Allosteric Compounds May Enhance Gal-3 Ligand Binding Kd through a None CRD Site Interaction AGS-905 – non-carbohydrate compound enhanced Gal-3 binding to integrin aMB2 by 200% Copyright 2019 Galectin Sciences, LLC Page 28
Slide 29: Allosteric Compounds Attenuating Galectin-3 Expression in THP-1 and Paca-2 Models
Allosteric Compounds Attenuating Galectin-3 Expression in Inflammatory THP-1 Macrophage and Paca-2 Cell Model Copyright 2019 Galectin Sciences, LLC Page 29
Slide 30: Allosteric Attenuating MCP-1 in Inflammatory THP-1 Macrophage
Allosteric Attenuating MCP-1 in Inflammatory THP-1 Macrophage Copyright 2019 Galectin Sciences, LLC Page 30
Slide 31: Intellectual Property Portfolio
Intellectual Property Portfolio Building a Proprietary Family of Compositions and Use Patents: 1. Composition of matter, International PCT submitted March 2017 2. Composition of matter, 2nd International PCT submitted May 2018 3. Composition and use of matter, 3rd International PCT submitted May 201
Slide 32: Next Steps: CMC scale-up, COA Characterizations, and Animal model Proof of Concept
Next Steps: CMC scale-up, COA Characterizations, and Animal model Proof of Concept API and Product manufactured • Scale up of 2-3 leading compositions - Synthesis optimization – on going • QC – Methods specifications and validation - on going • Stability & Formulations - on going Proof of concept in
Slide 33: Thank You
Thank You Eliezer Zomer, Ph.D. Galectin Therapeutics Inc. VP Drug Discovery & Manufacturing zomer@galectintherapeutics.com Raphael Nir, Ph.D. SBH Sciences Inc. President and Chief Scientific Officer rnir@sbhsciences.com Copyright 2019 Galectin Sciences, LLC Page 33