Galectin Therapeutics (GALT) 8-K Phase 1 Clinical Trial Results Of GR-MD-02, A

Phase 1 Clinical Trial Results Of GR-MD-02, A

Galectin-3 Inhibitor, In Patients Having Non-Alcoholic

Steatohepatitis (NASH) With Advanced Fibrosis

Stephen

A.

Harrison

1

,

Naga

P.

Chalasani

2

,

Eric

Lawitz

3

,

Smitha

Marri

2

,

Mazen

Noureddin

4

,

Arun

J.

Sanyal

5

,

Thomas

D.

Schiano

6

,

Mohammad

S.

Siddiqui

5

,

Brent

A.

Neuschwander-Tetri

7

,

Peter

G.

Traber

8,9

1

Brooke

Army

Medical

Center,

Fort

Sam

Houston,

TX;

2

Indiana

University

School

of

Medicine,

Indianapolis,

IN;

3

The

Texas

Liver

Institute, University of Texas Health Science Center, San Antonio, TX;

4

University

of

Southern

California,

Los

Angeles,

CA;

5

VCU

Medical

Center,

Richmond,

VA;

6

Icahn

School

of

Medicine

at

Mount

Sinai,

New

York,

NY;

7

St.

Louis

University,

St.

Louis,

MO;

8

Galectin

Therapeutics,

Norcross,

GA;

9

Emory

University

School

of

Medicine,

Atlanta,

GA

AASLD Abstract No. 57

Exhibit 99.1

Author Disclosures

•

Stephen A. Harrison –

Advisory Committees or Review Panels; Merck, Nimbus

Discovery, NGM Bio, Fibrogen. Grant/Research Support: Merck, Genentech;

Speaking and Teaching: Merck, Gilead, Janssen, AbbVie.

•

Naga P. Chalasani –

Consulting: Salix, AbbVie, Lilly, Boerhinger-Ingelham,

Aegerion; Grant/Research Support: Intercept, Lily, Gilead, Cumberland, Galectin

•

Eric Lawitz –

Advisory Committees or Review Panels: AbbVie, Achillion

Pharmaceuticals, BioCryst, Biotica, Enanta, Idenix Pharmaceuticals, Janssen,

Merck & Co, Novartis, Santaris Pharmaceuticals, Theravance, Vertex

Pharmaceuticals; Grant/Research Support: AbbVie, Achillion Pharmaceuticals,

Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline,

Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co,

Novartis, Presidio, Roche, Santaris Pharmaceuticals, Vertex Pharmaceuticals;

Speaking and Teaching: Gilead, Kadmon, Merck, Vertex

•

Arun J. Sanyal –

Advisory Committees or Review Panels: Bristol-Myers, Gilead,

Abbott, Ikaria; Consulting: Salix, Immuron, Exhalenz, Nimbus, Genentech,

Echosens, Takeda; Grant /Research Support: Salix, Genentech, Genfit, Intercept,

Ikaria, Takeda, GalMed, Novartis, Gilead; Independent Contractor; UpToDate,

Elsevier

•

Brent A. Neuschwander-Tetri –

Advisory Committees or Review Panels:

Boehringer-Ingerheim

•

Peter G. Traber –

Management Position: Galectin Therapeutics

•

The following people have nothing to disclose: Smitha Marri, Mazen Noureddin,

Thomas D. Schiano, Mohammad S. Siddiqui

2

Presenter Disclosure Slide

“The view(s) expressed herein are those of the author(s) and

do not reflect the official policy or position of Brooke Army

Medical Center, the U.S. Army Medical Department, the U.S.

Army Office of the Surgeon General, the Department of the

Army, Department of Defense or the U.S. Government.”

3

Background

•

Advanced liver fibrosis and cirrhosis are unmet medical

needs

•

NASH is the most common liver disease in the US and a

growing cause of cirrhosis requiring liver transplantation

•

Galectin-3 is a protein that binds to terminal galactose

residues on glycoproteins and is highly expressed in

macrophages

•

Knockout mouse experiments have shown that galectin-3

is a critical protein in fibrogenesis in multiple organs,

including liver fibrosis due to toxins and NASH

•

GR-MD-02 is a complex carbohydrate drug containing

terminal galactose residues that binds to galectin-3 and

inhibits its function

4

Pre-Clinical:

GR-MD-02 Has Therapeutic Effect On NASH

With Fibrosis In Mouse Model*

5

Normal

NASH:Control

NASH:GR-MD-02

GR-MD-02 Effects

NAFLD Activity Score

•

Fat

•

Cell death

•

Inflammation

Collagen

(Fibrosis)

Pico Sirius Red

Galectin-3

Protein

Galectin-3

H & E

*Traber PG and Zomer E. Therapy of Experimental NASH and Fibrosis with Galectin Inhibitors. PLOS ONE 2013;8:e83481

Pre-Clinical:

GR-MD-02 Reversed Cirrhosis And Improved Portal

Hypertension In Thioacetamide-Treated Rat Model*

6

Vehicle-Treated

GR-MD-02-Treated

(90 mg/kg, 1/W x 4)

*Traber

PG,

Chou

H,

Zomer

E,

Hong

F,

Klyosov

A

Fiel

M-I,

Friedman,

SL.

Therapy

of

Regression

of

fibrosis

and

reversal

of

cirrhosis

in

rats

by

galectin

inhibitors

in

thioacetamide-induced

liver

disease.

PLOS

ONE

2013;8:e75361.

Collagen

N=10

N=10

Portal Pressure

N=10

N=10

N=10

A Multi-Center, Partially Blinded, Maximum Tolerated Multiple Dose

Escalation, Phase 1 Clinical Trial to Evaluate the Safety of

GR-MD-02 in Subjects with Non-Alcoholic Steatohepatitis (NASH)

with Advanced Hepatic Fibrosis

•

Overall Objective:

•

Evaluate safety and pharmacokinetics of GR-MD-02 to provide

information and support to design a Phase 2 clinical program to

assess efficacy of GR-MD-02 in patients with NASH with advanced

fibrosis and cirrhosis. 

•

Clinical trial sites

•

Brooke Army Medical Center, Fort Sam Houston, TX

•

Indiana University School of Medicine, Indianapolis, IN

•

The Texas Liver Institute, San Antonio, TX

•

University of Southern California, Los Angeles, CA

•

VCU Medical Center, Richmond, VA

•

Icahn School of Medicine at Mount Sinai, New York, NY

•

St. Louis University, St. Louis, MO

•

Study Sponsor: Galectin Therapeutics Inc

7

Methods:

Three Cohort Design Of Phase 1 Clinical Trial

•

Subjects:

Biopsy

proven

NASH

with

Brunt

Stage

3

fibrosis

•

Design:

•

Blinded, placebo controlled, sequential dose escalation

•

Three cohorts: 2, 4, and 8 mg/kg lean body weight administered

by IV infusion over one hour

•

Primary

Endpoints:

Safety

and

Pharmacokinetics

•

Exploratory

Endpoints:

Potential

serum

biomarkers

8

1

st

Infusion

2

nd

Infusion

3

rd

Infusion

4

th

Infusion

Week 6-7

Pharmacokinetics

Pharmacokinetics

Biomarkers

Cohort 1

Cohort 2

Cohort 3

Cohort 1

(2 mg/kg)

Cohort 2

(4 mg/kg)

Cohort 3*

(8 mg/kg)

Enrolled

8

10

13

Completed

8

9

9

Pending Completion

by end of December

--

--

4

Completed Patients

Age Range (Mean)

40-64 (54)

34-69 (51.5)

44-69 (61)

Sex (M/F)

2/6

6/4

5/4

BMI (Mean)

39

39.6

33.2

BMI

30

8/8

9/9

5/9

Diabetes

6

4

7

9

Results:

Patient Characteristics

* Enrollment of cohort 3 terminated at 13 patients since sufficient

information obtained for phase 2 trial design

Results:

Safety Data On Completed Patients

10

Cohort 1

(2 mg/kg)

Cohort 2

(4 mg/kg)

Cohort 3

(8 mg/kg)

Active

Placebo

Active

Placebo

Active

Placebo

Completed protocol

6

2

7

2

6

3

Serious Adverse Events

0

0

0

0

0

0

TEAE’s probably related

0

0

0

0

0

0

TEAE’s possibly related

0

2

2

0

0

1

•

Therapy Emergent Adverse Events, possibly related to study drug were

reported in 3 subjects who received placebo and 2 subjects who received

GR-MD-02.  All adverse events were mild (grade 1) and transient.

•

An independent Data Safety Monitoring Board (DSMB) reviewed all data

after first and second cohorts.

Results:

Mean GR-MD-02 Plasma Concentration-Time Profiles

After First And Fourth Doses In All Three Cohorts

11

•

Proportional increase in drug coverage (AUC) for 2 mg/kg, 4 mg/kg,

and first dose of 8 mg/kg

•

Increase in AUC after four doses of 8 mg/kg indicates a saturable

compartment model

Cmax

µg/mL

T1/2

H

AUC

µg*h/mL

2 mg/kg x1

16.3

19.9

573

2 mg/kg x4

17.7

20.5

645

4 mg/kg x1

30

19.8

1039

4 mg/kg x4

31

19.5

1075

8 mg/kg x1

99.5

18.2

2449

8 mg/kg x4

169.9

18.4

4909

Pharmacokinetics Indicates 8 mg/kg dose Is Within The Upper

Range Of The Targeted Therapeutic Window

12

Target

Therapeutic

Window

•

The best therapeutic dose in mouse NASH was between 10 and 30 mg/kg

•

Relationship between AUC and dose shows mouse and human equivalency

AUC of Human 8 mg/kg dose

AUC of Human 2 mg/kg dose

Results:

Exploratory Serum Biomarkers

•

There are no validated serum biomarkers for evaluation of potential

therapeutic changes over time in NASH or fibrosis

•

A panel of serum tests were evaluated to explore potential

biomarkers for use in future studies

•

Most of the putative biomarkers showed high variability within the

same individual in placebo and GR-MD-02 patients, rendering them

not useful as reliable biomarkers

•

CK-18

(M30

and

M65),

TGF-

,

Osteopontin,

VEGF,

IP-10,

IL-6,

IL-8,

TNF-

,

CD-40

ligand,

metalloproteinases,

INF-

,

Endothelin-1

•

The ELF scores were not significantly changed relative to placebo

•

Earlier results in this patient population that suggested changes in

certain biomarkers were not evident with increased numbers of

placebo patients for comparison

•

FibroTest

®

, a composite score that has been correlated with the

extent of liver fibrosis, was significantly reduced by GR-MD-02

treatment in cohort 3.

•

Includes

following

serum

levels:

alpha-2-macroglobulin,

haptoglobin,

apolipoprotein

A1,

gamma

glutamyl

transpeptidase,

and

total

bilirubin

13

Results:

FibroTest

®

(FibroSure

®

) Scores

14

*     Placebo values were combined after showing that there was no difference between different time points

**   Statistical test: Three groups versus placebo, ANOVA with Dunnett’s test for multiple comparisons

***  Statistical test: Versus placebo, two-sided t-test

p < 0.05

p < 0.01

ns

ns

ns

Placebo

GR

2

nd

dose

GR

4

th

dose

+ 14 da

GR

4

th

dose

+ 3 da

GR

4

th

dose

+ 14 da

GR

4

th

dose

+ 3 da

Cohort 3**

Cohort 1***

Cohort 2***

Results:

Alpha-2 Macroglobulin Serum Levels

15

p < 0.005

p < 0.001

p < 0.05

Placebo

GR

2

nd

dose

GR

4

th

dose

+ 14 da

GR

4

th

dose

+ 3 da

GR

4

th

dose

+ 14 da

GR

4

th

dose

+ 3 da

Cohort 3**

Cohort 1***

Cohort 2***

*     Placebo values were combined after showing that there was no difference between different time points

**   Statistical test: Three groups versus placebo, ANOVA with Dunnett’s test for multiple comparisons

***  Statistical test: Versus placebo, two-sided t-test

ns

ns

Summary

•

Administration of 2, 4, and 8 mg/kg lean body weight

of GR-MD-02 intravenously for four doses over 6

weeks was safe and well tolerated in NASH patients

with advanced fibrosis

•

PK analysis demonstrated 8 mg/kg achieves targeted

therapeutic dosing range derived from animal studies

•

Analysis of most putative serum biomarkers showed high

variability in both placebo and drug groups and are not felt

to be useful in future studies

•

Changes in the FibroTest were seen in the high dose

cohort 3, attributable to a reduction in alpha-2

macroglobulin.

16

Phase 2 Clinical Trial Plans

•

A Phase 2 clinical trial is planned based on:

•

Pre-clinical efficacy

•

Phase 1 safety and tolerability

•

Phase 1 PK and animal model/human dose equivalency

•

Phase 1 evidence of pharmacodynamic effect at high dose

•

The company has informed the study investigators that it has

met with FDA to discuss Phase 2 trial design

•

Preliminary Phase 2 clinical trial design

•

Target patient population: Cirrhosis due to NASH

•

Study endpoints will include those that are closely associated with

outcomes in patients with cirrhosis

•

Primary endpoint:

Hepatic venous pressure gradient (HVPG)

•

Secondary endpoint:

Morphometric analysis of collagen on liver

biopsies

•

Other secondary endpoints will include non-invasive tests to evaluate

for correlation with HVPG and liver collagen

•

Timeline: Study is planned to be initiated in second quarter of 2015 and

an RFP has been responded to by 4 recognized CROs

17