 2014
Annual Stockholder Meeting May 14, 2014
NASDAQ: GALT
www.galectintherapeutics.com
©
2014 Galectin Therapeutics Inc
Exhibit 99.1 |
 Forward-Looking Statement Disclaimer
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,”
“estimate,”
“could,”
“expect”
and
others.
They are based on our current expectations and are subject to factors and
uncertainties which could cause actual results to differ materially from
those described in the statements. These statements include those
regarding
strategies
and
potential
therapeutic
benefits
of
GR-MD-02
and
expectations
regarding
clinical
trials,
including
the
future
enrollment
of
patients
and
the
timing
of
results.
These
statements
also
include expectations regarding our pipeline, patents and spending. Factors that
could cause our actual performance to differ materially from those discussed
in the forward-looking statements include, among others, future
pre-clinical and clinical results may differ materially from past results, and there is no
guarantee
that
our
trials
will
lead
to
positive
outcomes
or
that
GR-MD-02
will
ever
be
approved
by
the
FDA. We may experience delays in our trials and we may have difficulty
enrolling patients. We may experience delays in our trials, and we may
have difficulty enrolling patients and processing the resulting data.
Future
phases
or
future
clinical
studies
may
not
begin
or
produce
positive
results
in
a
timely
fashion, if at all, and could prove time consuming and costly. Plans regarding
development, approval and marketing of any of our drugs are subject to
change at any time based on the changing needs of our company as determined
by management and regulatory agencies. Strategies and spending projections
may change, and our expectations regarding patents may not be accurate.
Regardless of the results of current or future studies, we may be
unsuccessful in developing partnerships with other companies or obtaining
capital that would allow us to further develop and/or fund any studies or trials. To date, we have
incurred operating losses since our inception, and our ability to successfully
develop and market drugs may be impacted by our ability to manage costs and
finance our continuing operations. For a discussion of additional factors
impacting our business, see our Annual Report on Form 10-K for the year ended
December
31, 2013, and our subsequent filings with the SEC. You should not place undue
reliance on forward-looking statements. Although subsequent events may
cause our views to change, we disclaim any obligation to update
forward-looking statements.. 2
©
2014 Galectin Therapeutics | NASDAQ:GALT |
 Drugs
are natural complex carbohydrates that bind to galectin-3 and block
interactions with natural ligands ©
2013 Galectin Therapeutics NASDAQ:GALT
3
Galacturonic Acid
Rhamnose
Galactose
Mannose
GR-MD-02
(simplified schematic)
GM-CT-01
(simplified schematic)
•
Galectin-3 is most important in pathological situations, is widely expressed, but
highest in immune cells (macrophages)
•
In areas of acute or chronic inflammation and fibrogenesis, the gal-3 expression
is markedly increased. The majority of cancers express high levels of
galectin-3 •
•
Produced from
apple pectin
Produced from guar
gum |
 Our
Pipeline Of Galectin-3 Inhibitors ©
2014 Galectin Therapeutics | NASDAQ:GALT
4
*Galectin Sciences, LLC
Clinical Focus
Stage of Development
Drug
Indication
Discovery
Pre-clinical
Phase 1
Phase 2
Phase 3
Fibrosis
GR-MD-02
NASH (Fatty liver
disease) with advanced
fibrosis
Lung fibrosis
Kidney fibrosis
Cardiovascular fibrosis
Cancer Immunotherapy
GR-MD-02
Melanoma
Galectin-3 Inhibitors
GR-MD-03
Subcutaneous
GR-MD-04
Oral
G-XXX*
Oral |
 All
Chronic Liver Diseases Lead To Fibrosis Example: Liver Fibrosis In Fatty Liver
Disease (NASH) ©
2014 Galectin Therapeutics | NASDAQ:GALT
5
Stage 1
Stage 2
Stage 3
Stage 4
Patient
Liver
biopsy
Healthy
Fatty
Fibrosis
Cirrhosis
Liver failure
Bleeding
Encephalopathy
Edema
Asymptomatic
Only therapy for
patients with
cirrhosis is liver
transplantation
Bridging Fibrosis
Cirrhosis
Portal/Central
Pericellular/Central
(High Mag)
Blue=fibrosis
Occurs over decades |
 GR-MD-02, A Galectin-3 Inhibitor, Has Therapeutic
Effect On NASH With Fibrosis In Mouse Model
©
2014 Galectin Therapeutics | NASDAQ:GALT
6
Normal
NASH:Control
NASH:GR-MD-02
GR-MD-02 Effects
Disease Activity Score
•
•
•
Collagen
(Fibrosis)
Galectin-3
Protein
Improvement is linked to decreased tissue Galectin-3
Collagen Stain
Gal-3 Stain
Normal Stain
Fat
Cell death
Inflammation |
 GR-MD-02 Reversed Cirrhosis in Rat Model
7
•
Animal model
presented a very
high hurdle
for drug
treatment
•
Cirrhosis induced
with high dose toxin
and continued
throughout drug
treatment
•
Treatment with four,
once weekly doses of
GR-MD-02
Broad bands of
collagen with nodule
formation (N)
indicates advanced
fibrosis and cirrhosis
Reduction in
collagen with thin
and broken bands
(arrow) indicates
resolving fibrosis
and cirrhosis
©
2014 Galectin Therapeutics
NASDAQ:GALT
GR-MD-02
Vehicle |
 GR-MD-02 Is A Galectin-3 Inhibitor That Reduces
Collagen Synthesis And Increases Collagen
Degradation In Pre-Clinical Models
©
2014 Galectin Therapeutics | NASDAQ:GALT
8
Fibrosis
Restoration to Normal
Fibrosis results from increased
collagen and other matrix protein
synthesis with little to no change in
collagen degradation.
Fibrosis can resolve either by a
reduction in collagen synthesis or an
increase in degradation. The
combination would increase rate of
resolution.
Liver Fibrotic Tissue Homeostasis
+/-
+
Normal
In the normal liver, collagen and
matrix protein synthesis matches
degradation to provide appropriate
amount of extracellular matrix.
Collagen Synthesis
Collagen Degradation
=
Collagen Synthesis
Collagen Degradation
Collagen Synthesis
Collagen Degradation |
 GR-MD-02 Is Being Developed For The Indication Of
NASH With Advanced Fibrosis (Stage 3 and 4)
9
©
2014 Galectin Therapeutics | NASDAQ:GALT
Obesity/Insulin Resistance/Diabetes
Steatosis (fatty liver)
NASH (inflammation, cell death)
Stage 1 2 3
Fibrosis
Stage 4
Cirrhosis
•
No certainty of progression from early to late disease in an individual
•
Late disease much closer to clinical outcomes
•
Surrogates of clinical outcomes are better developed for late disease
•
GR-MD-02 reduces inflammation, ballooning and fat in NASH and reduces
existing fibrosis and reverses cirrhosis in animal models
Early Disease
Late Disease
Clinical Outcomes
Complications
Transplant
Death
Targeting Late Disease |
 Biopsy proven NASH with advanced fibrosis (stage 3)
Cohort has 8 patients (6 active, 2 placebo, blinded)
Starting
dose
of
2
mg/kg
lean
body
weight
(equivalent
to
80
mg/m
);
Phase 1 Clinical Trial Of GR-MD-02 In NASH With
Advanced Fibrosis: Fast Track FDA Designation
©
2014 Galectin Therapeutics | NASDAQ:GALT
10
0
28
35
42
56
70
Day
Infusion
-1
Biomarkers
Biomarkers
Patient inclusion:
Design:
Dose:
Primary endpoints:
Safety
Pharmacokinetics
Secondary endpoints:
Disease-related serum biomarkers to assess for
potential treatment effect
http://clinicaltrial.gov/ct2/show/NCT01899859?term=GR-MD-02&rank=2
2
Infusions at days 0, 28, 35 and 42. |
 Patient Characteristics, Safety and
Pharmacokinetics: Cohort 1
Patient Characteristics
•
•
•
•
11
©
2014 Galectin Therapeutics | NASDAQ:GALT
Pharmacokinetics
•
•
•
GR-MD-02 at a dose of 2 mg/kg
(80 mg/m
) was safe and well tolerated
See
presentation
for
full
results: http://bit.ly/QAcJbz
Patient Safety
•
•
•
There were no Serious Adverse Events
There were no Treatment Emergent
Adverse Events in patients receiving GR-
MD-02 that were attributed to the drug
There were no treatment emergent
laboratory or ECG findings
2
6 women and 2 men
Ages 40-64 (mean=54)
Mean body mass index (BMI)=39
Diabetes Mellitus in 6 patients
GR-MD-02 blood levels were consistent
between individuals with a t
1/2
of 20 hours
Blood levels not significantly different after
single or multiple infusions
The total drug exposure in humans given 2
mg/kg was approximately 40% of the total
drug exposure of the lowest dose used in
the mouse NASH model which was
therapeutic.
(obese >30) |
 Major
Pathological Processes in NASH ©
2014 Galectin Therapeutics | NASDAQ:GALT
12
Steato-Hepatitis (NASH Activity)
Fibrosis/Cirrhosis
Do Not Always Correlate in Same Patient
•
Can have high NASH activity score with minimal fibrosis
•
Can have advanced fibrosis/cirrhosis with minimal NASH activity
We measured serum biomarkers of both major pathological processes
•
Ballooning of liver cells (cell
death/apoptosis)
key
hallmark
•
Fat in liver cells (steatosis)
•
Immune cell infiltration (inflammation)
•
Increase
in
collagen/matrix
•
Disruption
of
architecture
•
Liver
cell
nodules |
 Serum
Biomarkers Of Fibrosis In NASH ©
2014 Galectin Therapeutics | NASDAQ:GALT
13
Composite Scores
FibroTest™
(FibroSURE™)
Individual Markers
Exploratory*
ELF (Enhanced Liver Fibrosis)
Score
Hyaluronic Acid
* Indicates that there is some evidence
that suggests they are increased in
fibrosis, but not confirmed in sufficient
number of patients or studies
•
Indirect
biomarker
of
fibrosis
•
Age and gender, Alpha-2-
macroglobulin, Haptoglobin,
Apolipoprotein A1, GGTP, Total
bilirubin
•
Matrix polysaccharide
•
Direct marker
•
Correlates to fibrosis
•
Direct
biomarker
of
fibrosis
•
Hyaluronic acid
•
TIMP1 (tissue inhibitor of
metalloproteinase-1)
•
P3NP (amino terminal
propeptide of type III pro-
collagen)
•
TGF-
•
Lumican
•
Osteopontin
•
Matrix Metalloproteinases
For
more
information
and
references
on
biomarkers:
http://bit.ly/1jzFK50 |
 FibroTest
™
(FibroSURE
™
)
Scores
Significantly
Decreased In GR-MD-02 Treated Patients
©
2014 Galectin Therapeutics | NASDAQ:GALT
14
One patient on GR-MD-02 had scores < 0.08 which was highly
discordant with biopsy (stage 3). Patient had high haptoglobin
which is known for false negative test.
Note: While the numbers are small, exploratory statistics have been
performed to evaluate differences using a one-sided t-test and
confirmed using a non-parametric test, Mann-Whitney
FibroTest
™
has
been
shown
to:
1)
Correlate
with
stage
of
fibrosis;
2)
Assess
fibrosis
regression;
3)
Assess
fibrosis
progression;
4)
Predict
liver-related
mortality
See
presentation
for
full
results:
http://bit.ly/QAcJbz |
 Serum
Biomarkers of NASH Inflammation and Injury ©
2014 Galectin Therapeutics | NASDAQ:GALT
15
Cellular Injury
Serum Transaminases
•
•
•
•
Cytokeratin 18
•
•
Cell Death (Apoptosis)
Key cytokines*
•
•
•
Exploratory**
•
•
•
•
•
Inflammatory Cytokines
* Evidence of association with human NASH and importance
in pathogenesis, particularly as products of macrophages
** Some evidence of association with human and/or animal
NASH in at least one publication
For
more
information
and
references
on
biomarkers:
IL-6
IL-8
TNF-
INF-
Endothelin-1
IP-10
VEGF
CD40-ligand
ALT and AST
Enzymes released from liver cells
2/3 of NASH patients have normal
levels at any given time
Entire spectrum of disease can be
seen with normal levels
A circulating biomarker of
cell death
Predictive of NASH
severity
http://bit.ly/1jzFK50 |
 Interleukin-6 Levels Were Significantly Reduced In
GR-MD-02 Treated Patients
©
2014 Galectin Therapeutics | NASDAQ:GALT
16
•
Pro-Inflammatory cytokine secreted by T cells and macrophages.
•
GR-MD-02 treated patients had significant reduction when compared to
placebo See
presentation
for
full
results:
http://bit.ly/QAcJbz |
 GR-MD-02 Treatment Appears To Improve Both Major
Pathological Processes In NASH
©
2014 Galectin Therapeutics | NASDAQ:GALT
17
•
Improvement in Fibrosis Biomarkers: There was a statistically significant
reduction in Fibrotest™
and trends towards a reduction in ELF score and
hyaluronic acid
•
Improvement in Inflammation Biomarkers: There were statistically significant
reductions in IL-6, IL-8 and TNF-
, all important cytokines in NASH
•
Improvement in Cell Death Biomarkers:
A patient subset with high ALT levels
indicative of more cellular injury had improvement in CK-18
Steato-Hepatitis (NASH Activity)
Fibrosis/Cirrhosis
•
Ballooning of liver cells (cell
death/apoptosis)
key
hallmark
•
Fat in liver cells (steatosis)
•
Immune cell infiltration (inflammation)
•
Increase in collagen/matrix
•
Disruption of architecture
•
Liver cell nodules
See
presentation
for
full
results:
http://bit.ly/QAcJbz |
 Summary of Findings From Cohort 1
•
GR-MD-02 was safe and well tolerated at 2 mg/kg (80 mg/m
) 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
•
Key composite biomarkers of fibrosis improved after four doses of
GR-MD-02 •
Key inflammatory cytokines were decreased after four doses of
GR-MD-02 •
Patients with greater cellular injury as indicated by elevated ALT levels, had a
marked decrease in CK-18, a cell death biomarker
•
Galectin-3 blood levels do not correlate with disease activity and are not a
biomarker of drug effect in patients with NASH with advanced fibrosis
In addition to being safe and well tolerated, GR-MD-02 improved
biomarkers of fibrosis, inflammation and liver cell injury in patients with
NASH with advanced fibrosis
18
©
2014 Galectin Therapeutics | NASDAQ:GALT
2 |
 Phase
1 Clinical Trial Of GR-MD-02 In NASH With Advanced Fibrosis: Second and
third cohort ©
2014 Galectin Therapeutics | NASDAQ:GALT
19
0
28
35
42
56
70
Day
Infusion
-1
BM/FS
BM/FS
Cohort
Patients
(A/P)
6/2
10*
21
28
35
49
63
0
-1
1
(2 mg/kg)
20**
21
28
35
49
63
0
-1
Timing
of
reporting
results:
•
Cohort 2: Around end of July
•
Cohort 3: November
38
BM
BM
BM/FS
38
BM
BM
BM
2
(4 mg/kg)
BM=Biomarkers
FS=FibroScan®
* 6/10 had FibroScan®
** Anticipate all will have FibroScan®
3
(8 mg/kg) |
 Competition in NASH: Different Indications and
Clinical Trial Endpoints
20
NASH (inflammation, cell death)
Stage 1
2 3 Fibrosis
Stage 4
Cirrhosis
Early Disease
Late Disease
Clinical Outcomes
Complications
Transplant
Death
©
2014 Galectin Therapeutics
NASDAQ:GALT
•
Focus is on improving
NAFLD Activity Score (8
points total):
•
Fat (3 pts.),
Ballooning (2 pts.),
Inflammation (3 pts.)
•
FLINT (NIDDK and
Intercept)
•
Other trials (Genfit,
Galmed, Conatus)
•
Focus is on stopping
progression or reversing
fibrosis
•
Gilead Trials (stop
progression)
•
LOL-2 (Lysyl oxidase-like-2) mAb
(GS-6624): Monoclonal antibody
that blocks the enzyme which
cross links collagen fibers
•
Galectin Therapeutics Trials
(stop progression and reverse
fibrosis) |
 Fibrosis Program Summary
•
First liver fibrosis indication: NASH with advanced fibrosis and/or
cirrhosis
•
Phase 1 trial indicates positive effects on fibrosis and NASH activity
(inflammation and cell death)
•
Controlled phase 2 clinical trial program to follow completion of phase
1 trial.
•
The results of the first cohort suggest that 2 mg/kg is a safe, well-tolerated
dose that has indication of anti-fibrotic and anti-inflammatory
effect. Therefore, this defines at least one potential dose level for phase
2 clinical trials •
Other Organ Fibrosis
•
Strong pre-clinical efficacy results in lung, kidney and cardiovascular
fibrosis •
Considering prospects for entering clinical development
•
Ongoing discussions with large pharmaceutical companies
•
Discussions
will
provide
foundation
for
partnering
opportunities
at
the
most
opportune time
21
©
2014 Galectin Therapeutics
NASDAQ:GALT |
 Our
Pipeline Of Galectin-3 Inhibitors ©
2014 Galectin Therapeutics | NASDAQ:GALT
22
Clinical Focus
Stage of Development
Drug
Indication
Discovery
Pre-clinical
Phase 1
Phase 2
Phase 3
Fibrosis
GR-MD-02
NASH (Fatty liver
disease) with advanced
fibrosis
Lung fibrosis
Kidney fibrosis
Cardiovascular fibrosis
Cancer Immunotherapy
GR-MD-02
Melanoma
Galectin-3 Inhibitors
GR-MD-03
Subcutaneous
GR-MD-04
Oral
G-XXX*
Oral
*Galectin Sciences, LLC |
 The
Vast Majority of Cancers Secrete Large Amounts of Galectins Which Have Multiple
Roles in Tumor Pathogenesis
23
©
2014 Galectin Therapeutics
NASDAQ:GALT
•
Tumor cell invasion:
extracellular matrix
adhesion & detachment
•
Metastasis:
cell invasion and migration
•
Angiogenesis
•
Tumor immunity has
recently been shown to be
critically affected by
galectins |
 Cancer Therapy Strategy
•
Focus on cancer immunotherapy based on the hypothesis that
galectin inhibitors will enhance efficacy of immunotherapies
•
Metastatic melanoma is initial cancer indication
•
In US 76,000 new diagnoses and 9,100 deaths annually
•
5% five year survival for metastatic disease
•
Even with newly approved drugs, still a substantial unmet medical need
•
We have sought collaborations with institutions that have:
•
Demonstrated clinical trial expertise in melanoma
•
Tumor immunology basic science research
•
Ability to conduct clinical trials and assist in funding
•
Collaboration established
•
Robert W. Franz Cancer Research Center, Earle A. Chiles Research
Institute (EACRI) Providence-Portland Medical Center, Portland Oregon
•
Joint patent application with exclusive license to Galectin Therapeutics
24
©
2014 Galectin Therapeutics
NASDAQ:GALT |
 Checkpoint inhibitors plus GR-MD-02 boosts anti-
tumor immunity, reduce tumor size and increase
survival in mouse cancer models
25
*p<0.05
aCTLA-4 = anti-CTLA-4 mAb [ipilimumab in humans (Yervoy, BMS)]
aPD-1 = anti-PD-1 mAb [positive results in clinical trials, BMS,
Merck] Unpublished data 2013: Stefanie N. Linch, Melissa J. Kasiewicz, Peter G.
Traber, and William L. Redmond, Galectin Therapeutics and Earle A. Chiles
Research Institute (EACRI), Portland Oregon ©
2014 Galectin Therapeutics
NASDAQ:GALT
*p<0.05
Also effective in breast cancer, melanoma, and sarcoma
TC-1 (prostate)
TC-1 (prostate) |
 Phase
1B Clinical Trial in patients with advanced melanoma using GR-MD-02 in
combination with Yervoy®
(ipilimumab): Actively Enrolling
26
1
23
43
64
85
Day
Infusion:
GR-MD-02
followed
by
Yervoy®
at
standard
doses
Patient
inclusion:
Advanced
melanoma
with
indication
for
Yervoy®
treatment
Design: 3+3 dose escalation (3 patients if no adverse events); 10 patients treated
with maximum
tolerated
dose
Dose:
Starting
dose
of
1
mg/kg
Endpoints:
•
•
•
Followed every 12 weeks for survival
Biopsy
Biopsy
©
2014 Galectin Therapeutics
NASDAQ:GALT
http://clinicaltrial.gov/ct2/show/NCT02117362?term=GR-MD-02&rank=1
Safety;
Pharmacokinetics
Tumor
response:
immune
response
RECIST
criteria
Biological
responses
including
memory
CD4+
T-cells,
memory
CD8+
T-cells,
melanoma
specific
T-cells,
and
composition
of
tumor
immune
infiltrate
from
tumor
biopsies
when
available. |
 Cancer Therapy Summary
•
Two immunotherapy agents have been approved for use to
date, with many more vaccines and activators in development
•
Our strategy is to leverage world class expertise in basic tumor
immunology and in the conduct of melanoma clinical trials.
27
©
2014 Galectin Therapeutics
NASDAQ:GALT
•
Providence
Portland
Medical
Center
and
Earle
A.
Chiles
•
Initial funding of clinical trial by PPMC/EACRI. Galectin is providing
GR-MD-02 study drug, reference to its IND, and PK analysis
•
Ongoing discussions with large pharmaceutical companies in
the immunotherapy space to seek a partnering opportunity at
the most opportune time
Research
Institute
(EACRI)
Ongoing
pre-clinical
studies;
IND
accepted for phase 1B clinical trial in patients with advanced
melanoma treated with a combination of Yervoy and GR-MD-02
: |
 Financial Key Facts –
As of May 9, 2014
28
Trading Symbol
Nasdaq: GALT
Corporate Headquarters
Norcross, GA (suburb of Atlanta)
Fiscal Year End
December 31
Accounting Firm
McGladrey LLP
Stock Price; 52 Week Range
$10.23 $3.90 -
$19.11
Shares Outstanding
21.9 million
Daily Volume (50 day average)
527,000 shares
Market Capitalization
$224 million
Debt
$0
Cash & Equivalents (March 31, 2014)
$36.6 million
Estimated Spending in 2014
$14.5 million
©
2014 Galectin Therapeutics
NASDAQ:GALT |
 Summary
•
Liver fibrosis program has advanced from a concept presented
three years ago at Annual Meeting to Phase 1 human results
showing safety and evidence of disease effect
•
Melanoma immunotherapy program has strong pre-clinical
results with an active Phase 1B clinical trial underway
•
Pipeline of other fibrosis indications and new anti-galectin drugs
is robust
•
Intellectual property strong
•
Patent attorneys are confident that GR-MD-02 and treatment
indications do not infringe on other companies’
patents
•
In fibrosis, Galectin has four issued patents and continues to advance
additional patent submissions related to GR-MD-02
•
Strong financial position to complete Phase 1 and potentially
Phase 2 depending on trial design to be determined based on
Phase 1 results and discussions with clinical experts and FDA.
29
©
2014 Galectin Therapeutics | NASDAQ:GALT |
 THANK YOU!
30
©
2014 Galectin Therapeutics | NASDAQ:GALT |