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): March 11, 2013
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
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 7 – REGULATION FD
Item 7.01 Regulation FD Disclosure.
On March 11, 2013, Galectin Therapeutics Inc. (the “Company”) posted a slide presentation on its website that contains a corporate summary of the Company’s business. The slide presentation, which is being furnished and not filed, is attached hereto as Exhibit 99.1.
The information in this report is being furnished pursuant to this Item 7.01 and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, and it shall not be deemed incorporated by reference in any filing under the Securities Act of 1933 or under the Exchange Act, whether made before or after the date hereof, except as expressly set forth by specific reference in such filing to this report.
SECTION 9 – FINANCIAL STATEMENTS AND EXHIBITS
Item 9.01 Financial Statements and Exhibits.
(a) Financial Statements of Businesses Acquired.
Not applicable.
(b) Pro Forma Financial Information.
Not applicable.
(c) Shell Company Transactions.
Not applicable.
(d) Exhibits.
| Exhibit Number |
Description | |
| 99.1 | Slide Presentation dated March 11, 2013 | |
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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: March 11, 2013 | By: | /s/ Peter G. Traber, M.D. | ||||||
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| Peter G. Traber, M.D. | ||||||||
| President, Chief Executive Officer & Chief Medical Officer | ||||||||
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| Exhibit 99.1 |
Galectin Therapeutics
Corporate Summary
March 11, 2013
NASDAQ: GALT
www.galectintherapeutics.com
Forward Looking Statements
Galectin Therapeutics
This presentation contains, in addition to historical information, statements that look forward in time or that express management’s beliefs, expectations or hopes. Such statements are 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 risks and uncertainties that could cause actual results to differ materially from those described in the statements. These statements include our plans, expectations and goals regarding drugs in development, clinical trials and regulatory approval for any of our drugs or treatments, related market opportunities for our drugs, potential benefits of our drugs, estimates regarding cash and liquidity, and estimates regarding those impacted by NASH and liver fibrosis. Our plans, expectations and goals regarding drugs in development, clinical trials and regulatory approval are subject to factors beyond our control. Our clinical trials may not begin or produce positive results in a timely fashion, if at all, and any necessary changes during the course of such trials could prove time consuming and costly. We may have difficulty in enrolling candidates for testing and we may not be able to achieve the desired results. Upon receipt of regulatory approval for any drug or treatment, we may face competition with other drugs and treatments that are currently approved or those that are currently in development, which could have an adverse impact on our ability to achieve revenues from the approved indication. 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. Estimates regarding the potential benefits of our drugs and the potential market for any of our drugs may be inaccurate and, to the extent the estimates are correct, we may not be successful in achieving revenues from any such drugs, as the successful marketing of any approved drugs will be subject to strong competition within the health care industry and patient and physician acceptance of our drugs as safe, affordable and effective. 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 most recent Annual Report on Form 10-K 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.
© 2013 Galectin Therapeutics NASDAQ:GALT 2
What We Do
Galectin Therapeutics
Clinical stage biopharmaceutical company targeting fibrotic diseases and cancer with novel compounds that inhibit galectin proteins
Galectin proteins are important in the development and promotion of many fibrotic and neoplastic diseases
Currently in clinical trials with 2 compounds
GR-MD-02 for the indication of NASH (Fatty Liver Disease) with advanced liver fibrosis: Phase 1
GM-CT-01 targeting cancer, enhance ability of immune system to kill cancer cells: Phase 2a clinical trial in combination with peptide vaccine for advanced melanoma
© 2013 Galectin Therapeutics NASDAQ:GALT 3
Investment Highlights
Galectin Therapeutics
Proprietary Compounds
First in class, proprietary compounds that inhibit galectin proteins
Complex carbohydrate drugs with favorable safety profile
GR-MD-02: Potential to treat non-alcoholic steatohepatitis (NASH) and other causes of liver fibrosis
GM-CT-01: Potential to enhance cancer immunotherapy
Validated Science
Pre-clinical models show galectins are critical targets for intended diseases with mechanisms that would be novel in the market
Large Market Opportunities
NASH and liver fibrosis indications would be first therapies for completely unmet medical needs, representing a multi-billion dollar market
Enhancing the ability of immune system to kill cancer cells is synergistic with many current and experimental therapies
Intellectual Property
Strong patent position
Sole ownership of compounds in development
No licenses granted
Experienced Management Team
Management team has collective experience in multiple biotech and pharmaceutical companies and relevant scientific areas
© 2013 Galectin Therapeutics NASDAQ:GALT 4
Key Facts
Galectin Therapeutics
Trading Symbol NasdaqCM: GALT
Corporate Headquarters Norcross, GA
Stock Price (3-6-2013); 52 Week Range $3.66 $1.60 - $6.00
Shares Outstanding (3-6-2013) 16.1 million
Daily Volume (50-day average at 3-6-2013) 60,862
Market Capitalization (2-15-2013) $58.44 million
Revenue TTM N/A
Debt (9-30-12) $0
Cash & Equivalents (9-30-12) $11.1 million
2013 Estimated Cash Burn Funded through 2013
Enterprise Value (3-6-2013) $67.6 million
Fiscal Year Ends December 31th
Accounting Firm McGladrey LLP
© 2013 Galectin Therapeutics NASDAQ:GALT 5
Galectin Therapeutics
Science of Galectins
Galectin Function
Galectin Inhibitors
Liver Fibrosis
Mechanism of Action
Regulatory and Clinical Plan
Competitive Positioning
Immune Enhancement in Cancer Therapy
Mechanism of Action
Regulatory and Clinical Plan
Competitive Positioning
© 2013 Galectin Therapeutics NASDAQ:GALT 6
Galectin Proteins Are Critical Participants In Pathogenesis of Many Fibrotic and Neoplastic Diseases
Galectin Therapeutics
Secreted Galectin Proteins*
Bind to cell surface and matrix glycoproteins (galactose residues)
Modulate cell signaling
Promote cell-cell interactions
Promote cell-matrix interactions
Markedly Increased in:
1. Inflammation
2. Fibrosis
3. Cancer
GALECTINS PROMOTE PATHOLOGY
Galectin-3 is most prominent galectin secreted in disease
*Secreted in small amounts normally by a number of cells, predominantly macrophages
For more detail on science of galectins go to website: http://bit.ly/Z1z0OD
© 2013 Galectin Therapeutics NASDAQ:GALT
Galectin Inhibitors: A New Class of Pathology Modulators
CONFIDENTIAL
Galectin Proteins
Galectin Inhibitor
Novel complex carbohydrate drugs that target secreted and membrane-associated galectins by virtue of high molecular weight
Strongest binding to galectin-3, most prominent galectin in disease processes
Binding to galectins disrupts function and modulates multiple cellular pathways in pathology representing a new class of therapeutic agents.
Low toxicity potential as a carbohydrate with no toxic metabolites
Two classes of compounds under development, GM-CT and GR-MD; strong patent portfolio; company owned, no licenses.
Discovery program underway to identify synthetic carbohydrate drugs
© 2013 Galectin Therapeutics NASDAQ:GALT 8
Regulatory Status of Drugs
CONFIDENTIAL
GM-CT-01
IND for use in combination with cancer chemotherapy
IMPD for use in melanoma in combination with peptide vaccine
Has been shown generally safe in over 100 human subjects
GMP API and GMP drug product in large supply; Drug Master File on file with FDA
GR-MD-02
IND submitted January 2013 for use in patients with non-alcoholic steatohepatitis (NASH) with advanced fibrosis
Pharmacology, pharmacokinetics, toxicology, and safety pharmacology support advancement into clinical trials
GMP API and GMP drug product in place for phase 1 clinical trial
Received OK from FDA to proceed with Phase 1 clinical trial
For more on compounds and discovery program go to website: http://bit.ly/ZiqEk4
© 2013 Galectin Therapeutics NASDAQ:GALT 9
Science of Galectins
Galectin Function
Galectin Inhibitors
Liver Fibrosis
Mechanism of Action
Regulatory and Clinical Plan
Competitive Positioning
Immune Enhancement in Cancer Therapy
Mechanism of Action
Regulatory and Clinical Plan
Competitive Positioning
© 2013 Galectin Therapeutics NASDAQ:GALT 10
Galectin-3 Is A Critical Protein Target For Therapy of Liver Fibrosis
Galectin-3 is produced in large amounts by fibrotic liver (animal and human)
Galectin-3 is essential in mice for the development of liver fibrosis
Fibrosis due to toxin exposure or fatty liver does not occur in mice that lack the galectin-3 gene
Galectin inhibitors reverse experimental fibrosis in rats induced by both fibrosis and fatty liver (Galectin data)
Galectin-3 is also critical for fibrosis in other tissues including kidney, lung, and heart.
To review data and literature in more detail go to website: http://bit.ly/14xDpKJ
© 2013 Galectin Therapeutics NASDAQ:GALT 11
NASH and Liver Fibrosis are Multi-Billion Dollar Markets In US Alone
The ONLY current therapy for advanced fibrosis (cirrhosis) is liver transplantation
No approved medical therapy for fibrosis
While there are treatments for some underlying etiologies (Hepatitis C and B), there is no approved therapy for NASH
Transplants (6,291*)
Wait List (17,000**)
Death From Cirrhosis (44,677#)
Cirrhosis (400,000##)
NASH: 9-15 Million& Hepatitis C, Hepatitis B, Alcohol
* Performed in US in 2010 (UNOS)
* * Prevalence in US 2010 (UNOS)
#Deaths in 1998 (AASLD Workshop, 2001)
##Prevalence in US 1976-1980 (NIDDK)
&Prevalence in US 2011 (NIH)
© 2013 Galectin Therapeutics NASDAQ:GALT 12
GR-MD-02 markedly improved NASH activity score and eliminated fibrosis in a mouse model of NASH
Liver Comparison
Liver Collagen Comparison
Vehicle x200
GR-MD-02 x200
Vehicle x200
GR-MD-02 x200
Quantitative Assessment of NASH Activity Quantitative Assessment of Collagen
NAFLD Activity score 7 6 5 4 3 2 1 0 P<0.01 Vehicle GR-MD-02
Sirius red-positive area (%) 1.25 1.00 0.75 0.50 0.25 0.00 P<0.001 Vehicle GR-MD-02
© 2013 Galectin Therapeutics NASDAQ:GALT 13
Treatment with GR-MD-02 Markedly Reduces Galectin-3 in NASH Mice
Immunohistochemistry for detection of Galectin-3 (Galectin-3 detected with brown stain)
Vehicle
x200
GR-MD-02
x200
© 2013 Galectin Therapeutics NASDAQ:GALT
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Galectin Inhibitor GR-MD-02 Effectively Treats Toxin-Induced Liver Fibrosis in Rats
Liver fibrosis induced in all rats by injection of chemical toxin (thioacetimide) for 8 weeks
Treatment with vehicle alone for four weeks (Control) shows robust fibrosis
Treatment with GR-MD-02 for four weeks shows dramatic regression of fibrosis
Galectin Therapeutics Data
© 2013 Galectin Therapeutics NASDAQ:GALT
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Targeting Anti-Galectin Therapy In The Progression of NASH
Decades
Development of Obesity
Insulin Resistance/Diabetes
Steatosis (fatty liver)
NASH
Fibrosis
Cirrhosis
Because of effect on inflammation in NASH and ability to reduce existing fibrosis, our clinical program will target NASH patients with advanced fibrosis
© 2013 Galectin Therapeutics NASDAQ:GALT
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Galectin Therapeutics
NASH Development Program: GR-MD-02
2012 2013 2014
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
IND (FDA; proceed with phase 1)
NASH
Pre-Clinical Completed
Phase 1 NASH trial
Phase 2 NASH Trial
(timing to be determined)
First patient enrolled
Top line results
Fast Track Designation to be filed; Breakthrough Designation application following Phase 1
Phase 1 Trial: Patient Inclusion: Biopsy proven NASH with advanced fibrosis Design: Four weekly IV doses per cohort with escalation to target dose Primary Endpoint: Patient safety Secondary Endpoints: Serum biomarkers to assess for pharmacodynamic effect; can provide some evidence of efficacy
Phase 2 Trial: Patient Inclusion: Biopsy proven NASH with advanced fibrosis
Design: Randomized, controlled, double blinded study with at least six months of therapy
Primary Endpoint: Liver biopsy evaluated for percent area collagen
Secondary Endpoints: Safety; Serum biomarkers, MR-fat and elastography
© 2013 Galectin Therapeutics NASDAQ:GALT 17
Galectin Therapeutics
Competition in NASH
Most drugs in development focus on improving NASH activity score (fat, inflammation, and cell death)
Minimal or boarder line results with PPAR agonists (pioglitazone), Vitamin E, pentoxyiphlline.
Raptor Pharmaceuticals: cysteamine in adolescent NASH (P2)
Intercept Pharmaceuticals: Obeticholic acid (P2)
Mochida: ethyl icosapentate (P2)
Few companies are focused on fibrosis which is the key cause of liver failure in patients
Gilead: Lysyl oxidase-like-2 mAb (GS-6624); Initiated Phase 2 trials in 2012 in patients with NASH and fibrosis, top line data Q3 2015
Galectin: GR-MD-02
© 2013 Galectin Therapeutics NASDAQ:GALT 18
Galectin Therapeutics
Science of Galectins
Galectin Function
Galectin Inhibitors
Liver Fibrosis
Mechanism of Action
Regulatory and Clinical Plan
Competitive Positioning
Immune Enhancement in Cancer Therapy
Mechanism of Action
Regulatory and Clinical Plan
Competitive Positioning
© 2013 Galectin Therapeutics NASDAQ:GALT 19
The Vast Majority of Cancers Secrete Large Amounts of Galectins Which Have Multiple Roles in Tumor Pathogenesis
Galectin Therapeutics
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
The “Galectin Effect” protects tumors from immune system
© 2013 Galectin Therapeutics NASDAQ:GALT
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Tumors Evade the Immune System Using the “Galectin Effect” and GM-CT-01 Reverses This Effect
Galectin Therapeutics
Galectin-3 secreted by tumor cells binds to surface of T-cells and inhibits cytokine secretion
Treatment with GM-CT-01 blocks Galectin-3 and restores T-cell cytokine secretion and tumor killing
To review data and literature in more detail go to website: http://bit.ly/YD3zuM
Experiments performed by Dr. Pierre van der Bruggen of the Ludwig Institute in Brussels,
Belgium in collaboration with Galectin Therapeutics
© 2013 Galectin Therapeutics
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Galectin Therapeutics
Preclinical efficacy and clinical safety data sufficient to obtain an IMPD for treatment of metastatic melanoma to test the efficacy of blocking the “Galectin Effect”
Melanoma “Proof of Concept” Trial: Patients: Metastatic melanoma
Design: Two stage Phase 2a (6x2 cohorts in stage 1 and 23x2 cohorts in stage 2) Regimen: Prime with melanoma specific peptide vaccine then treat with GM-CT-01 Endpoint: Partial or complete response by imaging Study site: Ludwig Institute, Brussels Belgium Study funding: Ludwig Institute
Group 2 patients have additional injection of GM-CT-01 in cutaneous tumors
More information available on clinicaltrials.gov: http://1.usa.gov/ZiHQpO
© 2013 Galectin Therapeutics
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Tumor Immune Enhancement Development Program
Galectin Therapeutics
2012 2013 2014
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
Phase I/II Melanoma Trial*
GM-CT-01
Top line results in Stage 1**
Stage 2 TBD
At conclusion of Stage 1 of study:
Continue to Stage 2 with some efficacy
Consider Phase 2b controlled trial with strong efficacy
Seek partnership with company with marketed or late stage cancer immunotherapy
Pursue Partnering Discussions
*Conducted in Belgium under an IMPD. Not conducted under FDA IND, but there is an open IND for GM-CT-01
** Estimate of Stage 1 results modified because of slow recruitment; only one site active; 5 patients enrolled
© 2013 Galectin Therapeutics
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Immune Enhancement by Blocking “Galectin Effect” is Synergistic With Many Emerging Cancer Immunotherapies
Galectin Therapeutics
Enhancing the ability of the immune system to recognize and kill tumor cells is a very active area in the personalized approach to cancer therapy
Two agents have been approved for use to date, more vaccines and activators in development
Dendritic cell vaccine: Provenge® (Dendreon)
T-cell activator (CTLA4 receptor mAb): Yervoy® (Ipilimumab, BMS)
Our compound reverses the “Galectin Effect” by which tumors inhibit the immune system and may be synergistic with all tumor immunotherapies
While tumor vaccines are patient and tumor specific, reversal of the “Galectin Effect” appears to be universal
The tumor vaccine market is forecast to be over $7 billion by 2015
© 2013 Galectin Therapeutics
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Key Company Milestones: 12 months
Galectin Therapeutics
NASH with Advanced Fibrosis (Fatty Liver Disease)
3/1/13: FDA provided OK to proceed with human studies
5/13: Initiate Phase 1 NASH with advanced fibrosis trial
Q1 2014: Phase 1 NASH trial results
Q2 2014: Initiate Phase 2 NASH trial
Top line data from Phase 2 trial TBD based on design
Cancer Immunotherapy
Phase 2a metastatic melanoma trial, first patient infused 5/12
Five patients currently enrolled; stage 1 data likely available by end of Q2 2013
© 2013 Galectin Therapeutics
25 NASDAQ:GALT
Galectin Therapeutics
Investment Highlights
Proprietary Compounds
First in class, proprietary compounds that inhibit galectin proteins
Complex carbohydrate drugs with favorable safety profile
GR-MD-02: Potential to treat non-alcoholic steatohepatitis (NASH) and other causes of liver fibrosis
GM-CT-01: Potential to enhance cancer immunotherapy
Validated Science
Pre-clinical models show galectins are critical targets for intended diseases with mechanisms that would be novel in the market
Large Market Opportunities
NASH and liver fibrosis indications would be first therapies for completely unmet medical needs, representing a multi-billion dollar market
Enhancing the ability of immune system to kill cancer cells is synergistic with many current and experimental therapies
Intellectual Property
Strong patent position
Sole ownership of compounds in development
No licenses granted
Experienced Management Team
Management team has collective experience in multiple biotech and pharmaceutical companies and relevant scientific areas
© 2013 Galectin Therapeutics NASDAQ:GALT 26
Galectin Therapeutics
Appendix
© 2013 Galectin Therapeutics
NASDAQ:GALT
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Galectin Therapeutics
Experienced Management Team
Peter G. Traber, MD President, CEO, CMO
Over 25 years experience in biomedicine and pharmaceutical industries in research and development, clinical medicine, management and leadership, and business development. Medical expertise in liver disease
GlaxoSmithKline (CMO), Un of Pennsylvania (CEO), Baylor College of Medicine (CEO)
Harold H. Shlevin, PhD COO
Over 25 years of senior management experience in the development and commercialization of pharmaceuticals, diagnostics and vaccines
Solvay Pharmaceuticals (CEO), CIBA Vision Ophthalmics (co-founder), Tikvah Therapeutics (Founder, CEO), Georgia Institute of Technology’s Advanced Technology Development Center, Altea Therapeutics Corporation
Eliezer Zomer, PhD EVP, Product Development
Over 30 years experience in biotechnology engineering and regulatory in pharmaceuticals and diagnostics.
Koor Biotechnologies, Charm Sciences, Glycogenesis , HU Medical School (Jerusalem), Harvard University
Thomas A. McGauley CFO (acting)
Over 10 years in accounting and finance with life science and technology companies
PricewaterhouseCoopers, Pro-Pharmaceuticals, deCode Genetics
J. Rex Horton Executive Director, Regulatory Affairs and Quality Assurance
Over 20 years of experience working in the biotech and life sciences industries, regulatory affairs and manufacturing.
Solvay Pharmaceuticals, Chelsea Therapeutics, Georgia Institute of Technology.
© 2013 Galectin Therapeutics
NASDAQ:GALT
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Galectin Therapeutics
CONFIDENTIAL
Galectin Proteins Promote Interactions Between Glycoproteins with Terminal Galactose Residues
TYPE STRUCTURE GALECTIN
One-CRD 1,2,5,7,10,11,13,14,15
3
Two-CRD 4,6,8,9,12
Carbohydrate Recognition Domain
Galactose-containing oligosaccharides
One-CRD galectins (dimer)
Galectines-3 (oligomers)
Two-CRD galectins
cell–cell and
cell–matrix interactions
lattice formation
outside cell
Inside cell
signal transduction
Galectin proteins have both intracellular and extracellular functions
© 2013 Galectin Therapeutics
NASDAQ:GALT
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Galectin Therapeutics
CONFIDENTIAL
Rationale for Galectin Protein Targeting with Complex Carbohydrate Agents
The theoretical basis for complex carbohydrate drugs is that terminal galactose residues bind to galectin proteins in the context of a macromolecular structure, similar to the situation with glycoproteins
Galactomannan (GM-CT-01)
Galacto-Rhamnoglucuronate (GR-MD-02)
© 2013 Galectin Therapeutics
NASDAQ:GALT
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Intellectual Property
Galectin Therapeutics
GM-CT Class (current NCE is GM-CT-01)
US Composition of matter patent Issued 2011 (expires 2023)
Five US issued method of use patents in combination with cancer therapy for increased efficacy and reduced side effects
International Patents: 14 granted and 5 pending
Method of use in liver fibrosis issued 2012 (expires 2026)
Method of use in NASH patent pending (priority 2011)
GR-MD Class (current NCE is GR-MD-02)
Method of use in liver fibrosis patent issued (expires 2026)
Composition of matter patent pending (priority 2011)
Method of use in NASH patent pending (priority 2011)
All intellectual property generated in house with no encumbrances
No established generic pathway for such complex carbohydrate drugs
© 2013 Galectin Therapeutics
NASDAQ:GALT
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Inhibition of Gal-3 May Have Multiple Sites of Action in Therapy of NASH
Galectin Therapeutics
Cause of Liver Injury
Mediators
Inflammation
Fibrosis
Resolution
Metabolic Syndrome
Glucose Intolerance
Fat Accumulation
Impaired Lipid Metabolism
Hyperglycemia
Adipocytokines
Free Fatty Acids
T-Cell Hepatocyte Bile Duct Cell Macrophage
Gal-3 Gal-3 Gal-3
Lipo-peroxidation Products
Release of multiple inflammatory cytokines, including TGF-B1, a critical mediator of fibrosis
Quiescent Activated
Stellate Cell
Inflammation ceases
Gal-3 Cytokines
ECM Dissolution
MMPs
Extracellular Matrix
Stellate Cells Macrophages
Galectin
Gal-3 expression and activation of macrophages
Scavenger receptor increases cellular uptake of toxic products
Increases TGF-B1 receptor signaling
Promotes activation of stellate cells to myofibroblasts
GR-MD-02
Reduces Gal-3 and activation of macrophages; changes in macrophage subtypes?
Inhibit scavenger mechanism and reduce cellular toxicity
Reduce cell membrane TGF-B1 receptor activity
Reduces activation of stellate cells
? Effect on ECM dissolution; Macrophages
© 2013 Galectin Therapeutics
NASDAQ:GALT
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Examples of Therapeutic Approaches Under Investigation for Therapy of NASH
Galectins Therapeutics
General Mechanism
Obesity
Treat Diabetes and Insulin Resistance
Lipid Metabolism
Modulate the Immune System
Protease Inhibition
Bile salt metabolism
Anti-Oxidant / toxin metabolism
Anti-collagen cross-linking
Examples
Lifestyle, dieting
Pioglitazone
Aramchol & others
EGS21 (Enzo)
Pentoxifylline
GS-9450 (Gilead)
Colesevelam
Obeticolic acid
Vitamin E
MND-21 (Mochida)
Cysteamine
Lysyl oxidase-like-2 mAb (GS-6624, Gilead)
Comments
Can be beneficial; not effective in advanced NASH
Failed to achieve significant endpoints in phase 2 and phase 3 clinical trials, but some evidence of effect
Cholesterol inhibition, no clinical results
Abandoned after phase 2 trial
Non significant phase 3 results
Liver toxicity in phase 2: abandoned
Intestinal bile salt binder, Phase 2 trial failed
FXR agonist; Phase 2 coming to conclusion
Effective in NASH score in phase 3, but not fibrosis
Omega-3 fatty acid (phase 2 trial)
Phase 2 trial in adolescents underway
Initiated Phase 2 trials in 2012 in patients with NASH and fibrosis, top line data Q3 2015.
GR-MD-02 is well positioned with respect to competition
Most attractive mechanism: multiple sites of action in disease
Independent of hyperglycemia or hyperlipidemia
May reverse established fibrosis
Low toxicity potential as a carbohydrate with no toxic metabolites
© 2013 Galectin Therapeutics
NASDAQ:GALT
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Galectin Therapeutics
Other companies with galectin inhibitor programs
Galecto Biotech AG (Sweden): Discovery phase focusing on modified disaccharide molecule inhibitors. Development program focused on lung fibrosis.
LaJolla Pharmaceuticals (CA): In Jan. 2012, they purchased GCS-100 from Solana Therapeutics (formally Prospect Therapeutics, formally Glycogenesis). GCS-100 is a natural product compound with claims for binding galectins; focused on blood cancers; significant side effects reported; now progressing in development for cancer and kidney fibrosis
Mandel Med (Oakland, CA): Truncated galectin-3 protein; not progressed into human trials and no active program currently
© 2013 Galectin Therapeutics
NASDAQ:GALT
34
Capitalization
Galectin Therapeutics
Common Stock
Shares (9/30/12)
Common Shares 15,966,437
Preferred Series A (converted) 260,430
Preferred: Series B (converted) 2,000,000
Preferred: Series C (converted) 366,680
Warrants: Series B* 5,000,000
Other Warrants** 2,424,241
Options Outstanding*** 3,541,630
Total Outstanding 29,559,418
* Exercise Price: $3.00 (all controlled by 10X Fund)
** Weighted Average Exercise Price: $4.97
*** Weighted Average Exercise Price: $5.88
© 2013 Galectin Therapeutics NASDAQ:GALT
Total Outstanding
Management, Officers and Directors
10X Fund (includes Series B Shares)
Series A Shares
Series C Shares
Other Warrants and Options
Publicly Traded Warrants
Public Float