Galectin Therapeutics Inc. · NASDAQ:GALT
Galectin Therapeutics — Investor Presentation (March 2019)
44 slides from Galectin Therapeutics's investor presentation, March 2019
Slide 1: Corporate Overview
Corporate Overview March 2019 Harold H. Shlevin, Ph.D. Chief Executive Officer Jack W. Callicutt Chief Financial Officer NASDAQ: GALT www.galectintherapeutics.com 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
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 Summary
Galectin Summary • Galectin is advancing its lead compound, GR-MD-02 (belapectin), towards a Phase 3 trial in NASH Cirrhosis, First Patient ~ Fall, 2019 • NASH market opportunity estimated to reach $35 - $40 Billion/Year by 2025* • Proven biological activity in both Phase 2b and animal trials • Phas
Slide 4: Galectin Phase 3 Trial – NASH-RX
Galectin Phase 3 Trial – “NASH-RX” • Investigating NASH cirrhosis, a condition that is more closely linked to liver failure and its life-threatening implications than earlier stages of NASH • Have engaged leading NASH experts to provide advice and counsel to strengthen our plan for the NASH-RX Phase
Slide 5: Strong, experienced management team
Strong, experienced management team Harold H. Shlevin, Ph.D., CEO and President Jack W. Callicutt, CFO • Over 34 years of relevant experience • Solvay Pharmaceuticals, CEO • Over 27 years of relevant experience • CIBA Vision Ophthalmics (n/k/a Novartis Vision), SVP & co-founder • Reach Health, CFO,
Slide 6: Contents
Contents ▪ General NASH Competitive Landscape ▪ NASH Cirrhosis and GR-MD-02 ▪ Phase 2b Results ▪ Phase 3 plans ▪ Cancer Immunotherapy Combination ▪ Summary 6 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 7: NASH Disease Progression
NASH Disease Progression 7 Source: Torres DM, et al. Clin Gastroenterol Hepatol. 2012;10:837-858. 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 8: Industry Pipeline Is Relatively Less Crowded in Cirrhotic NASH
Industry Pipeline Is Relatively Less Crowded in Cirrhotic NASH GR-MD-02 Uniquely Positioned 8 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 9: Contents
Contents ▪ General NASH Competitive Landscape ▪ NASH Cirrhosis and GR-MD-02 ▪ Phase 2b Results ▪ Phase 3 plans ▪ Cancer Immunotherapy Combination ▪ Summary 9 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 10: Galectin is developing a compound for the most serious stages of the disease
Galectin is developing a compound for the most serious stages of the disease 10 Reprinted from: B Riley FBR Research, Feb., 2019 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 11: GR-MD-02 targets and disrupts the function of galectin-3
GR-MD-02 targets and disrupts the function of galectin-3, which plays a major role in diseases that involve organ fibrosis Central Role of Gal-3 in Multiple Pathological Processes Galectin proteins’ ability to dimerize creates the opportunity for galectins to link glycoproteins and form a lattice st
Slide 12: There is currently no treatment for NASH cirrhosis
There is currently no treatment for NASH cirrhosis, a progressive disease that can lead to significant mortality Compensated Cirrhosis Decompensated Cirrhosis Stage 1 Stage 2 Stage 3 and 4 NASH: No Varices Varices Develop Bleeding, Ascites, Encephalopathy Cell Death Fatty Liver Inflammation Fibrosis
Slide 13: Patients with NASH cirrhosis without varices are at high risk
Patients with NASH cirrhosis without varices are at high risk for severe complications and have a high degree of unmet need Compensated Cirrhosis Decompensated Cirrhosis Significance of Targeting NASH Cirrhosis Stage 1 Stage 2 Stage 3 and 4 without Varices:NASH: No Varices Varices Develop Bleeding,
Slide 14: NASH-CX Phase 2b trial design
NASH-CX was a randomized, double-blind, placebo-controlled phase 2b clinical trial that enrolled 162 NASH cirrhosis patients1 Phase 2b Trial Design Major Inclusion Criteria Dosing and Administration ○ NASH cirrhosis (biopsy) ○ No cirrhosis complications Every other ○ HVPG2 ≥ 6 mmHg ○ No or small var
Slide 15: Statistically significant reduction in HVPG at week 54
The GR-MD-02 2 mg/kg group showed a statistically significant reduction in HVPG from baseline to week 54 for patients without varices Mean Change from 0.8 mmHg -1.08 mmHg 0.15 mmHg Baseline to Week 541 p = 0.01 ns 13 Statistically 12 HVPG (mmHg) significant effect of 2 mg/kg dose 11 on change in HVP
Slide 16: 43% of patients without varices showed clinically relevant HVPG reduction
43% of patients without varices in the GR-MD-02 2mg/kg group showed a ≥2 mmHg and ≥20% decrease from baseline compared to 13% in the placebo group Percentage of Patients Who Had a Clinically Relevant Reduction in HVPG With: • ≥ 2 mmHg Decrease From Baseline AND • ≥ 20% Decrease From Baseline p = 0.0
Slide 17: Change in Hepatocyte Ballooning Score at Week 54
Patients in the 2 mg/kg treatment group showed statistically significant improvement of liver cell death on liver biopsy1 p = 0.03 p = 0.09 0.4 Ballooning Score at Week 54 Change in Hepatocyte In the total 0.2 population there was improvement in cell death, a n=54 n=54 critical feature of NASH 0.0 n
Slide 18: Percent New Varices Formation
Significantly fewer new varices developed in treatment groups versus placebo, and no patients in the 2 mg/kg treatment group developed new varices 20 p = 0.02 Percent New Varices Formation 15 Trial hit a clinically relevant endpoint 10 related to patient outcomes 5 6/33 0/25 0 Placebo GR-MD-02 2 mg/
Slide 19: Efficacy in two clinically meaningful endpoints
GR-MD-02 has demonstrated efficacy in two clinically meaningful endpoints, where no current therapies exist ▪ Portal hypertension (PH) is a critical, clinically important consequence of cirrhosis and responsible for the majority of associated complications • Portal pressures of ≥10 mmHg are associat
Slide 20: Portal Hypertension is the Main Driver of Decompensation
Portal Hypertension is the Main Driver of Decompensation 20 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 21: GR-MD-02 was safe and well-tolerated
GR-MD-02 was safe and well-tolerated ▪ No differences between treatment groups in the number of patients with treatment emergent adverse events (AEs), grade 3/4 AEs, serious adverse events (SAE), or grade 3/4 laboratory abnormalities ▪ All but 2 SAEs were unrelated to study drug; 2 patients in 8 mg/
Slide 22: Positive effects shown in a subset of patients in NASH-CX
Positive effects of GR-MD-02 shown in a subset of patients in the NASH-CX trial has allowed the company to reach its current Phase 3 development trajectory After incorporating advice and Phase 3 Trial Design guidance from the FDA, Galectin Target Patient Population announced on May 14, 2018 that the
Slide 23: Summary of GR-MD-02 in NASH Cirrhosis
Summary of GR-MD-02 in NASH Cirrhosis ▪ NASH-CX is the first clinical trial to show positive results in compensated NASH cirrhosis without esophageal varices • Clinically meaningful effect in reducing portal pressure in a subgroup of patients • Improvement in liver cell death, a key component of NAS
Slide 24: Contents
Contents ▪ General NASH Competitive Landscape ▪ NASH Cirrhosis and GR-MD-02 ▪ Phase 2b Results ▪ Phase 3 plans ▪ Cancer Immunotherapy Combination ▪ Summary 24 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 25: Galectin Phase 3 Trial – The NASH-RX Overview
Galectin Phase 3 Trial – “The NASH-RX” Overview • The focus and goal of the therapeutic program is to establish the efficacy & assess safety & tolerability of GR-MD-02 compared to placebo in reducing the development and progression of esophageal varices in patients with NASH cirrhosis. • The results
Slide 26: Galectin Phase 3 Trial – The NASH-RX Highlights
Galectin Phase 3 Trial – “The NASH-RX” Highlights • Parallel group, randomized, placebo-controlled, double-blinded, of either 2 mg/kg or 4 mg/kg GR-MD-02 or placebo administered by i.v. infusion every two weeks for two years to NASH Cirrhosis patients who did not have esophageal varices at baseline.
Slide 27: Galectin Phase 3 Trial – NASH-RX Milestones
Galectin Phase 3 Trial – “NASH-RX” Milestones • Next Steps: • Complete final contract with CRO • Complete drug supply manufacturing • Contract for developmental and reproductive toxicology studies • Key clinical study milestones: • Estimated First Patient ~ Fall, 2019 • Global Study: ~120+ sites, ro
Slide 28: Contents
Contents ▪ General NASH Competitive Landscape ▪ NASH Cirrhosis and GR-MD-02 ▪ Phase 2b Results ▪ Phase 3 plans ▪ Cancer Immunotherapy Combination ▪ Summary 28 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 29: GR-MD-02 in Combination Cancer Immunotherapy
GR-MD-02 in Combination Cancer Immunotherapy ▪ As a galectin-3 inhibitor, GR-MD-02 may represent a novel mechanism of action that is believed to be differentiated from the many other drugs being tested ▪ Potentially important advantages in combination immunotherapy • Enhancement of activity with mul
Slide 30: Immune suppression via galectin-3
Immune suppression via galectin-3
Slide 31: Melanoma best response
Melanoma best response * 100 2 mg/kg 4 mg/kg 8 mg/kg 50 0 -50 -100 * Previously reported 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 32: Responders to GR-MD-02/aPD-1 therapy have reduced Mo-MDSCs
Responders to GR-MD-02/aPD-1 therapy have reduced Mo-MDSCs post-Tx * Baseline Day 85 15 Mo-MDSC (cells 10^9/L) Mo-MDSC (cells 10^9/L) 0.6 0.6 *P=0.026 %Monocytes (CBC) NS 10 0.4 0.4 5 0.2 0.2 Baseline Non-Responder Responder 0 0.0 0.0 1 22 43 64 85 R R R R ay n- n- ay ay ay ay D D D D D no no * Data
Slide 33: Conclusions (clinical)
Conclusions (clinical) Combination GR-MD-02/aPD-1 immunotherapy ✓ Combination therapy was safe and well-tolerated ✓ Favorable ORR (n=21 pts) compared to aPD-1 monotherapy Biomarkers of response ✓ Increased baseline expression of PD-1+ on effector CD8 T cells associated with response ✓ Reduced Mo-MDS
Slide 34: Future Directions
Future Directions • Additional analysis of biomarkers correlate with clinical response • flow cytometry and mIHC • Expansion cohort (2019; 4 mg/kg GR-MD-02+pembro) • n=15 patients • 4 mg/kg dosing selected because immunological and anti-tumor responses were observed (and no increase in these at 8 mg
Slide 35: Contents
Contents ▪ NASH Cirrhosis ▪ Cancer Immunotherapy Combination ▪ Summary 35 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 36: Summary of Drug Development Program
Summary of Drug Development Program ▪ GR-MD-02 is a novel antigalectin-3 drug that may modulate the immune system and may improve multiple diseases ▪ NASH Cirrhosis is a major unmet medical need with a large potential market • Galectin-3 is important in development of NASH cirrhosis • NASH-CX trial
Slide 37: Summary of Drug Development Programs
Summary of Drug Development Programs ▪ Clinically meaningful improvement shown in Phase 2 study in primary program, NASH cirrhosis without varices • First randomized clinical trial of any drug to demonstrate statistically significant positive efficacy in compensated NASH cirrhosis without varices •
Slide 38: Thank you for your attention
Thank you for your attention Harold Shlevin, PhD - CEO Shlevin@galectintherapeutics.com Jack W. Callicutt – CFO Callicutt@galectintherapeutics.com 38 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 39: Supplemental Slides
Supplemental Slides 39 2019 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
Slide 40: Additional Considerations
Additional Considerations ▪ Large Institutional Shareholder Converts Preferred to Common ▪ $10 Million Line of Credit Unused yet and Extended until 2021 ▪ Exalenz Bioscience uses Data Collected on GALT Trial for AASLD Presentation ▪ Encouraging Results from Phase 1B trial with Keytruda in Advanced M
Slide 41: GR-MD-02 targets the ~230,000 NASH patients with cirrhosis and without varices
GR-MD-02 targets the ~230,000 NASH patients with cirrhosis and without varices Addressable Patient Population (2018 estimates, US and EU5) 1 2 3 4 Diagnosed NASH patients w/ Diagnosed NASH patients Adult NASH patients Diagnosed NASH patients Population cirrhosis with cirrhosis w/o varices ~23M ~9M ~
Slide 42: Why is the GR2 dose better than GR8? PK may hold the key
Why is the GR2 dose better than GR8? PK May hold the key This graph shows AUC versus dose for the mouse and the target therapeutic window from experiments I NASH mice. The dose chosen for the NAHS-CX study were informed from a phase 1 study in patients with NASH with advanced fibrosis. Predicted to
Slide 43: Change in HVPG from Baseline to End of Study Using AUC Range Groups
Change in HVPG from Baseline to End of Study Using AUC Range Groups This shows there is a significant difference from placebo in percent change of HVPG when compared to the GR8 (AUC<12K), but not when the AUC’s in the GR8 treatment group at an AUC of 12K defines an upper range of the therapeutic win
Slide 44: PK-PD Correlation between Mouse and Human
PK-PD Correlation between Mouse and Human A PK-PD relationship was developed based on experiments done in a mouse model of NASH1. AUCs for the GR2 dose and 8mg/kg GR-MD-02 dose were graphed with the house AUC values of 10, 30, 60, and 120mg/kg which were the doses used the mouse NASH model. Also sho
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