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8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

PURSUANT TO SECTION 13 OR 15(d)

OF THE SECURITIES EXCHANGE ACT OF 1934

Date of Report (Date of earliest event reported): November 10, 2014

 

 

GALECTIN THERAPEUTICS INC.

(Exact name of registrant as specified in its charter)

 

 

 

Nevada   001-31791   04-3562325

(State or Other Jurisdiction

of Incorporation)

  

(Commission

File Number)

  

(IRS Employer

Identification No.)

4960 PEACHTREE INDUSTRIAL BOULEVARD, Ste 240

NORCROSS, GA 30071

(Address of principal executive office) (zip code)

Registrant’s telephone number, including area code: (678) 620-3186

N/A

(Former name or former address, if changed since last report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

 

 

SECTION 8 – OTHER ITEMS

Item 8.01 Other Items.

On November 10, 2014, Galectin Therapeutics Inc. posted a corporate presentation regarding its Phase 1 clinical trial on its website that contains a summary of development of GR-MD-02 for Non-Alcoholic Steatohepatitis (NASH) With Advanced Fibrosis, which is attached as Exhibit 99.1.

SECTION 9 – FINANCIAL STATEMENTS AND EXHIBITS

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit Number

   

Description

99.1    Corporate presentation

 

- 2 -

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, Galectin Therapeutics Inc. has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

    Galectin Therapeutics Inc.
Date: November 10, 2014     By:   /s/ Jack W. Callicutt
      Jack W. Callicutt
      Chief Financial Officer

 

- 3 -

EX-99.1
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