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): February 6, 2018
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)) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
SECTION 7 – REGULATION FD
| Item 7.01 | Regulation FD Disclosure. |
On February 6, 2018, Galectin Therapeutics Inc. (the “Company) posted to its website three presentations which are attached hereto as Exhibit 99.1, Exhibit 99.2 and Exhibit 99.3.
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. |
(d) Exhibits.
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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: February 6, 2018 | By: | /s/ Peter G. Traber | ||||
| Peter G. Traber, M.D. | ||||||
| Chief Executive Officer | ||||||
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CORPORATE PRESENTATION February 6, 2018 NASDAQ: GALT www.galectintherapeutics.com Exhibit 99.1
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 potential therapeutic benefits of our drugs, expectations, plans and timelines related to our clinical trials, potential partnering opportunities and estimated spending for 2018 and beyond. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, our trials may not lead to positive outcomes or regulatory approval. We may experience delays in our trials, which could include enrollment delays. 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. We may be unsuccessful in developing partnerships with other companies or obtaining capital that would allow us to complete our clinical trials or further develop and/or fund any future studies or trials. To date, we have incurred operating losses since our inception, and our future success 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, 2016, 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. Forward-Looking Statements
Recognized leader in gastroenterology and hepatology University of Pennsylvania Chief of Gastroenterology; Chairman of Internal Medicine; CEO of Health System, Dean of Medicine Baylor College of Medicine, President and CEO GlaxoSmithKline, Senior Vice President and Chief Medical Officer Over 34 years of relevant experience Solvay Pharmaceuticals, CEO CIBA Vision Ophthalmics (n/k/a Novartis Vision), SVP & co-founder Tikvah Therapeutics, Founder and CEO CIBA-Geigy Pharmaceuticals Over 27 years of relevant experience Reach Health, CFO, Vystar Corporation, CFO, Corautus Genetics, Deloitte Over 34 years of relevant experience: Koor Biotechnologies, Charm Sciences, Glycogenesis, HU Medical School (Jerusalem), and Harvard University Over 28 years experience in regulatory affairs, clinical development and medical affairs UCB Inc., Abbott Laboratories, Solvay Pharmaceuticals Peter G. Traber, M.D., President, CEO, CMO Harold H. Shlevin, Ph.D., COO & Corporate Secretary Jack W. Callicut, CFO Eli Zomer, PhD, Pharm Development Adam Allgood, Pharm D., Clinical Development Rex Horton, Regulatory Over 26 years of experience; Director Regulatory Affairs at Solvay Pharmaceuticals and Chelsea Therapeutics; Georgia Institute of Technology Galectin is a Development Stage Biotech Company with an Experienced Team 3
Addressing Important Unmet Medical Needs 4 Advanced Fatty Liver Disease (NASH Cirrhosis) NASH global annual market could be $35-40 Billion by 2025 Competitively well positioned as one of the few companies focused on the most advanced form of NASH Our target indication of NASH cirrhosis may have 2.5M patients in US First and only positive phase 2 clinical data in target indication to date Combination Cancer Immunotherapy Large opportunity to improve results of immunotherapy of cancer Encouraging early clinical data with our drug in combination with KEYTRUDA with 5 of 8 objective responses (2 complete responses and 3 partial responses) in advanced melanoma
Primary Program is in NASH Cirrhosis Positive efficacy in compensated NASH cirrhosis without varices Combination Cancer Immunotherapy Encouraging early clinical data in combination with KEYTRUDA with 5 of 8 objective responses (2 complete responses (CR) and 3 partial responses (PR)) in advanced melanoma Psoriasis and Atopic Dermatitis Clinically significant effect in small open label studies Developing Treatments Where Galectin-3 Protein is Implicated in Disease Clinical Phase Studies with Galectin-3 Inhibitor GR-MD-02 5
80 - 100M 24 - 30M 1.5-2.5M 1.5-2.5M Estimated US Prevalence There is no Treatment for NASH Cirrhosis Fatty Liver NASH: Cell Death Inflammation Fibrosis 6 Many companies with clinical development programs Few companies with clinical development programs 1 Garcia-Tsao, G., Friedman, S., Iredale, J., Prinzani, M. Hepatology. 2010;51:14451449 Compensated Cirrhosis Decompensated Cirrhosis Stage 1 Stage 2 Stage 3 and 4 No Varices Varices Develop Bleeding, Ascites, Encephalopathy Low one year mortality (1-3%) ~50% one year mortality ≥6 >10 >12 Portal Pressure (mmHg)
Critical Importance of Esophageal Varices in NASH Cirrhosis Esophagus: No Varices Esophageal Varices Bleeding Esophageal Varices An important goal of treatment of patients with Stage 1, compensated cirrhosis without esophageal varices is to prevent progression to varices and complications 7
4 Liver-related complications (varices/bleeding, ascites, hepatic encephalopathy, liver-related death, or transplant) NASH-CX Clinical Trial Design Baseline Week 54 Primary Endpoint Portal Pressure: HVPG2 X X Secondary Endpoints Liver Biopsy3 X X Endoscopy (varices) X X Complications4 X X 1 All subjects were enrolled across 36 sites in the US 2 HVPG = Hepatic Venous Pressure Gradient 3 Histologic staging & quantitative morphometry for collagen 1 Major Inclusion Criteria NASH cirrhosis (biopsy) HVPG2 ≥ 6 mmHg No cirrhosis complications No or small varices (50:50) Every other week infusion x 26 8 Treatment #Patients Placebo 54 GR-MD-02 2 mg/kg 54 GR-MD-02 8 mg/kg 54 Additional trial data on website
NASH Cirrhosis Without Esophageal Varices at Baseline Placebo GR-MD-02 2 mg/kg GR-MD-02 8 mg/kg 13 9 8 10 11 12 n=33 Baseline Week 54 n=31 Baseline n=25 Week 54 n=23 n=23 Baseline n=22 Week 54 HVPG (mmHg) Statistically significant effect of 2 mg/kg dose on change in HVPG at baseline Mean Change from Baseline to Week 541 0.8 -1.08 p <0.01 0.15 ns 1 ITT with LOCF, ANCOVA with LSD Mean ± SEM 9
Responder Analysis in Patients Without Varices at Baseline p = 0.011 Placebo GR-MD-02 2 mg/kg 50% 10% 0% 4/31 20% 30% 40% 10/23 13% 43% 1 Chi Square Rigorous definition of efficacy because it requires a clinically important reduction in HVPG from baseline Percentage of Patients Who Had a Clinically Relevant Reduction in HVPG With: ≥ 2 mmHg Decrease From Baseline AND ≥ 20% Decrease From Baseline
Statistically Significant Improvement of Liver Cell Death on Liver Biopsy 1 ITT population Ordinal Logistic Regression Analysis Placebo GR-MD-02 2 mg/kg GR-MD-02 8 mg/kg p = 0.03 p = 0.09 0.4 0.2 0.0 -0.2 n=54 n=54 Mean ± SEM n=53 Change in Hepatocyte Ballooning Score at Week 54 1 11 In the total population there was improvement in cell death, a critical feature of NASH
Significantly Fewer New Varices Developed in Treatment Groups Versus Placebo Percent New Varices Formation Placebo GR-MD-02 2 mg/kg 6/33 0/25 p = 0.02 20 15 10 5 0 Trial hit a clinically relevant endpoint related to patient outcomes 1 Chi Square
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/kg group had SAEs that were possibly related to study drug There was one death due to complications of a surgical procedure that was unrelated to study drug There was a low patient dropout rate of 6% which suggests the drug was well tolerated. Only one patient was removed from study for an AE possibly related to study drug 13
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 Improvement in liver cell death, a key component of NASH Reduction in the development of new esophageal varices Drug was safe and well-tolerated 14 These results will propel development program to next stage Ongoing data analysis (pharmacokinetics of drug levels, serum biomarkers) and preparation of clinical study report Phase 3 clinical trial being designed to seek approval from FDA We believe program will be eligible for FDA “Breakthrough” designation; will be submitted when clinical study report completed Ongoing discussions with Pharma for potential partnerships
Primary Program is in NASH Cirrhosis Combination Cancer Immunotherapy Encouraging early clinical data in combination with KEYTRUDA with 5 of 8 objective responses (2 complete responses and 3 partial responses) in advanced melanoma Psoriasis and Atopic Dermatitis Small open label studies show clinically significant effect, demonstrating activity of drug in human disease Developing Treatments Where Galectin-3 Protein is Implicated in Disease Clinical Phase Studies with Galectin-3 Inhibitor GR-MD-02 15
Galectin-3 secreted by cancer cells into the tumor microenvironment reduces the ability of immune system to fight cancer Even with newly approved drugs, a substantial unmet medical need remains in melanoma and multiple other cancers Cancer Immunotherapy 16 - Providence Cancer Center in Portland, Oregon - Performed preclinical studies showing efficacy of GR-MD-02 with checkpoint inhibitors - Conducting and funding P1b clinical trial Additional information on website
Phase 1B Trial of GR-MD-02 Plus Pembrolizumab (KEYTRUDA) in Patients with Metastatic Melanoma and Other Cancers 17 GR-MD-02 used in combination with a flat dose (200 mg) of pembrolizumab in the following patients: Metastatic melanoma with progression after other treatment including pembrolizumab alone Recurrent or metastatic HNSCC with progression after other treatment d1 d22 d43 d64 d85 Every 3 weeks GR-MD-02 2 mg/kg (5 patients; completed) 4 mg/kg (3 patients; completed) 8 mg/kg (10 patients; underway) Pembrolizumab Imaging (CT/MRI/PET) Immune cells and markers
Clinical Results of GR-MD-02 plus Pembrolizumab (KEYTRUDA) Waterfall plot of best objective clinical response post treatment (RECIST 1.1) 18 * * Head and Neck CA Response rate of 62.5% in melanoma compares favorably to best response of KEYTRUDA alone of 33%
CT Scan Showing Resolution of a Large Intramuscular Melanoma Deposit Baseline Day 85 19
Multiple PET Scan Detected Melanoma Deposits Resolved 20 Baseline Day 169 Multiple tumors in legs All tumors resolved
Multiple PET Scan Detected Melanoma Deposits Resolved 21 Baseline Day 169 Multiple tumors throughout body (red arrows) All tumors resolved: normal contrast seen in heart, kidneys and bladder
GR-MD-02 in Combination Cancer Immunotherapy Many combination approaches are under investigation using marketed and experimental cancer immunotherapy drugs As a galectin-3 inhibitor, GR-MD-02 represents a novel mechanism of action, differentiated from the many other drugs that being tested Potentially important advantages in combination immunotherapy Enhancement of activity with multiple agents and tumors (pre-clinical) Potential novel and unique markers of anti-tumor activity Encouraging enhancement of tumor response in phase 1 study No increase adverse events when used in combination immunotherapy Cost of manufacture is relatively inexpensive compared to biologics Third patient cohort treated with GR-MD-02 8 mg/kg, which will enroll at least 10 additional patients, is well underway with results anticipated in mid-2018 22 Additional information on website
Developing Treatments Where Galectin-3 Protein is Implicated in Disease Clinical Phase Studies with Galectin-3 Inhibitor GR-MD-02 Primary Program is in NASH Cirrhosis Combination Cancer Immunotherapy Psoriasis and Atopic Dermatitis Small open label studies show clinically significant effect, demonstrating activity of drug in human disease
Activity of GR-MD-02: Moderate-to-Severe Plaque Psoriasis Psoriasis is immune-mediated chronic skin inflammation associated with NASH All 5 patients treated in Phase 2a open label trial showed improvement in disease activity by an average of 50% (one improved by 82%) Additional evidence that drug is effective in a human disease with increased galectin-3 24
25 Summary of Drug Development Program GR-MD-02 is a novel antigalectin-3 drug that can 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 is first and only positive phase 2 clinical data in target indication to date GR-0MD-02 was safe and well-tolerated and improved portal pressure, liver biopsy, and reduced development of varices GALT is competitively well positioned in the industry Combination cancer immunotherapy Galectin-3 important in cancer immunity with encouraging early clinical results Large opportunity to improve results of cancer immunotherapy Sufficient funding for operations into early 2019
Thank you!
GR-MD-02 for Indication of NASH Cirrhosis: NASH-CX Clinical Trial Results Supplemental Information to Corporate Presentation February 6, 2018 NASDAQ: GALT www.galectintherapeutics.com 2017 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com Exhibit 99.2
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,” “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 potential therapeutic benefits of our drugs, expectations, plans and timelines related to our clinical trials, potential partnering opportunities and estimated spending for 2018 and beyond. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, our trials may not lead to positive outcomes or regulatory approval. We may experience delays in our trials, which could include enrollment delays. 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. We may be unsuccessful in developing partnerships with other companies or obtaining capital that would allow us to complete our clinical trials or further develop and/or fund any future studies or trials. To date, we have incurred operating losses since our inception, and our future success 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, 2016, 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.
Developing Treatments Where Galectin-3 Protein is Implicated in Disease Clinical Phase Studies With Galectin-3 Inhibitor GR-MD-02 Primary Program is in NASH Cirrhosis (topic of this presentation) Combination Cancer Immunotherapy Investigator initiated phase 1b clinical trial of GR-MD-02 in combination with KEYTRUDA in advanced melanoma and other malignancies Encouraging early data with 5 of 8 responders (2 CR and 3 PR) in advanced melanoma Psoriasis and Atopic Dermatitis Small open label studies show clinically significant effect, demonstrating activity of drug in human disease
NASH Cirrhosis Development Program: Summary Gal-3 null mice are resistant to development of NASH 1 and liver fibrosis 1, 2 GR-MD-02 is a glycopolymer (polysaccharide), considered a Nonbiological Complex Drug (NBCD) that binds to galectin-3 protein, has strong patent protection, and is administered intravenously GR-MD-02 has robust efficacy in pre-clinical models of NASH and toxic cirrhosis, with action at multiple pathophysiological processes 3, 4 Well tolerated and safe in preclinical toxicology and clinical trials (2 P1, P2a and P2b) NASH-CX phase 2b clinical trial showed clinically meaningful positive results of GR-MD-02 in patients with NASH cirrhosis without esophageal varices NASH-CX trial identified endpoints and patient population that can form the basis of phase 3 trials in NASH cirrhosis without esophageal varices 1 Journal of Hepatology 2011;54:975-983 2 PNAS 2006;103:5060-5065 3 Traber PG and Zomer E.PLOS ONE 2013;8:e83481 4 Traber PG, Chou H, Zomer E, Hong F, Klyosov A Fiel M-I, Friedman, SL. PLOS ONE 2013;8:e75361.
80 - 100M 24 - 30M 1.5-2.5M 1.5-2.5M Estimated US Prevalence There is no Treatment for NASH Cirrhosis Fatty Liver NASH: Cell Death Inflammation Fibrosis 5 1 Garcia-Tsao, G., Friedman, S., Iredale, J., Prinzani, M. Hepatology. 2010;51:14451449 Compensated Cirrhosis Decompensated Cirrhosis Stage 1 Stage 2 Stage 3 and 4 No Varices Varices Develop Bleeding, Ascites, Encephalopathy Low one year mortality (1-3%) ~50% one year mortality ≥6 >10 >12 Many companies with clinical development programs Few companies with clinical development programs Portal Pressure (mmHg)
Critical Importance of Esophageal Varices in NASH Cirrhosis Esophagus: No Varices Esophageal Varices Bleeding Esophageal Varices An important goal of treatment of patients with Stage 1, compensated cirrhosis without esophageal varices is to prevent progression to varices and complications 6
NASH-CX Clinical Trial Design1 Every other week infusion X 26 Placebo (54) GR-MD-02 2 mg/kg (54) GR-MD-02 8 mg/kg (54) NASH cirrhosis (biopsy) HVPG ≥ 6 mmHg No cirrhosis complications No or small varices HVPG2 Liver Biopsy3 FibroScan MBT4 Complications5 Endoscopy X X X X X X X X X X X X X X 1 All subjects were enrolled across 36 sites in the US (Appendix 1) 2 HVPG = Hepatic Venous Pressure Gradient 3 Histologic staging & quantitative morphometry for collagen Primary endpoint Secondary endpoints Baseline Week 26 Week 54 4 MBT = 13C Methacetin Breath Test 5 Liver-related complications (varices/bleeding, ascites, hepatic encephalopathy, liver-related death, or transplant) Major Inclusion Criteria
Patient Populations: Total Group N = 290 Patients Screened N = 162 Patients Randomized N = 128 Screening Failures N = 54 Placebo (PLB) N = 54 2 mg/kg GR-MD-02 (GR2) N = 54 8 mg/kg GR-MD-02 (GR8) N = 3 Discontinued Treatment AE (1) Lost to follow up (0) Withdrew consent (1) Protocol mandate (1) N = 2 Discontinued Treatment AE (1) Lost to follow up (0) Withdrew consent (0) Protocol mandate (1) N = 6 Discontinued Treatment AE (5) Lost to follow up (1) Withdrew consent (0) Protocol mandate (0) Analyses Sets, PLB FAS/ITT (N= 54 ) mITT (N= 54) PP (N= 47) Analyses Sets, GR8 FAS/ITT (N= 54) mITT (N= 54) PP (N= 46) Analyses Sets, GR2 FAS/ITT (N= 54) mITT (N= 53) PP (N= 52) Demographic characteristics (age, gender, BMI, nationality, diabetes) and baseline HVPG measurements were balanced across the three treatment groups in study analysis sets
HVPG Primary Endpoint: Total Patient Population HVPG increased in placebo, whereas it decreased in treatment groups by end of study While there was a trend toward benefit with drug, it was not statistically significant
HVPG Primary Endpoint: Mild Portal Hypertension in Total Population Group Evaluation of mild portal hypertension was a pre-determined statistical analysis There was a statistically significant effect of both doses of GR-MD-02 There was no effect on those with high portal pressure (data not shown)
Patient Populations Based on Esophageal Varices Patients Screened: N = 290 Screening Failures N = 128 Baseline Esophageal Varices N = 80 (ITT/LOCF) No Baseline Esophageal Varices N = 81 (ITT/LOCF) 1 Discontinued before 1st dose 10 Discontinued during dosing without end of study HVPG CSPH N = 67 MPH N = 13 CSPH N = 41 MPH N = 40 Patients Randomized: N = 162 Demographic characteristics (age, gender, BMI, nationality, diabetes) and baseline HVPG measurements were balanced across the three treatment groups in study analysis sets ITT: 161 ITT/LOCF: 161 mITT: 151 PP: 145 Definitions: ITT = Intention to Treat ITT/LOCF = ITT/Last Observation Carried Forward mITT= ITT with end of study HVPG PP = Per Protocol MPH = Mild Portal Hypertension CSPH = Clinically Significant Portal Hypertension Note: All analyses done with ITT/LOCF; results were similar with other analysis sets Study Analysis Sets
NASH Cirrhosis Without Varices at Baseline (50% of total population) Drug effect was significantly dependent on dose*varices in total group (p<0.04) Presence or absence of esophageal varices is an important clinical finding Statistically significant effect of 2 mg/kg dose on absolute and percent change in HVPG in patients without baseline esophageal varices
Responder Analysis in Patients Without Varices at Baseline 1 Chi Square Percentage of Patients Who Had a Clinically Relevant Reduction in HVPG With: ≥ 2 mmHg Decrease From Baseline AND ≥ 20% Decrease From Baseline Rigorous definition of efficacy because it requires a clinically important reduction in HVPG from baseline
Statistically Significant Improvement of Hepatocyte Ballooning on Liver Biopsy Change in hepatocyte ballooning score at week 54 Mean ± SEM n=54 n=54 n=53 Total Study Patient Population2 2 ITT with LOCF (161) 1 Traber PG and Zomer E. PLOS ONE 2013;8:e83481 3 Ordinal Logistic Regression Analysis p = 0.033 p = 0.093 Placebo GR-MD-02 2 mg/kg GR-MD-02 8 mg/kg There was a statistically significant improvement in hepatocyte ballooning (liver cell death) with GR-MD-02 (2 mg/kg) and a strong trend with 8 mg/kg compared to placebo The reduction in ballooning hepatocytes with GR-MD-02 correlates with what was seen in NASH animal models1 NAFLD activity score had a trend towards improvement because of improved ballooning, but not statistically significant No differences in steatosis or inflammation scores No differences in fibrosis staging or % collagen on morphometry, but not powered for these endpoints
Cirrhosis Complications1 Patients with at least one complication PLB GR2 GR8 Comments Intention to Treat Group (n=161) 11 (54) 8 (53) 7 (54) No difference between groups No Baseline Esophageal Varices (n=81) 7 (33) 3 (25) 2 (23) No difference between groups New Esophageal Varices 6 0 1 p = 0.022, PLB vs GR2 p = 0.122, PLB vs GR8 p = 0.012, PLB vs GR2 + GR8 2 Chi Square In patients without varices, there were statistically significant fewer new varices that developed in treatment groups versus placebo 1 Complications Include: Development of new esophageal varices Progression to medium or large varices Variceal hemorrhage Clinically Significant Ascites Spontaneous bacterial peritonitis Overt Hepatic Encephalopathy Increase in CPT Score ≥ 2 MELT score ≥ 15 Liver Transplant Liver related death
Significantly Fewer New Varices Developed in Treatment Groups Versus Placebo Placebo GR-MD-02 2 mg/kg GR-MD-02 8 mg/kg 2 mg/kg plus 8 mg/kg 6/33 1/23 0/25 1/48 Percent New Varices Formation p = 0.02 p = 0.12 p = 0.01 Chi Square
Safety Results Total (n=162) PLB (n=54) GR2 (n=54) GR8 (n=54) All adverse events 1422 464 541 417 Grade 3-4 (patients (total events)) 31 (69) 10 (19) 10 (22) 11 (28) SAE1 (patients (total events)) 25 (39) 9 (13) 5 (10) 11 (16) Rx stopped due to AE 5 0 0 52 Death 1 0 13 0 Grade 3/4 lab (patients (total events)) 8 (15) 3 (3) 2 (2) 3 (10) 1 Two SAEs were determined by the PI to be possibly related to study drug (transient ischemic attack and worsening of hyponatremia, both GR8); All others SAEs were felt to be unrelated to study drug 2 Possibly related to drug: spasmodic cough (1); Unrelated to study drug: esophageal variceal bleeding (2), sepsis (1), pancreatitis (1) 3 Pulmonary embolism following hernia repair surgery, judged to be unrelated to study drug
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/kg group had SAEs that were possibly related to study drug There was one death due to complications of a surgical procedure that was unrelated to study drug There was a low patient dropout rate of 6% which suggests the drug was well tolerated. Only one patient was removed from study for an AE possibly related to study drug
Major Conclusions from NASH-CX Clinical Trial Results GR-MD-02 had a statistically significant and clinically meaningful effect in improving HVPG versus placebo in patients with NASH cirrhosis who did not have baseline esophageal varices Important drug effect in the total study population on liver biopsy, with a statistically significant improvement in hepatocyte ballooning (cell death) Statistically significant reduction in the development of new esophageal varices in drug-treated patients compared to placebo While there was a drug effect in both dosage groups on liver biopsy and in the mild portal hypertension group, there was a consistently greater and statistically significant effect of the 2 mg/kg dose GR-MD-02 appears to be safe and well tolerated in this one year, phase 2b clinical trial We believe this is the first large, randomized clinical trial of any drug to demonstrate a clinically meaningful improvement in portal hypertension or liver biopsy in patients with NASH cirrhosis without varices
Summary Conclusions and Next Steps 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 Improvement in liver cell death, a key component of NASH Reduction in the development of new esophageal varices Drug was safe and well-tolerated These results will propel development program to next stage Ongoing data analysis (pharmacokinetics of drug levels, serum biomarkers) and preparation of clinical study report Phase 3 clinical trial being designed to seek approval from FDA We believe program will be eligible for FDA “Breakthrough” designation; will be submitted when clinical study report completed Ongoing discussions with Pharma for potential partnerships
Appendix NASDAQ: GALT www.galectintherapeutics.com 2017 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com
22 Appendix 1: Deep Gratitude to Patient Volunteers and Clinical Study Sites
The Galectin-3 Inhibitor GR-MD-02 for Combination Cancer Immunotherapy Supplemental Information to Corporate Presentation February 6, 2018 NASDAQ: GALT www.galectintherapeutics.com 2017 Galectin Therapeutics | NASDAQ: GALT For more information, see galectintherapeutics.com Exhibit 99.3
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,” “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 potential therapeutic benefits of our drugs, expectations, plans and timelines related to our clinical trials, potential partnering opportunities and estimated spending for 2018 and beyond. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, our trials may not lead to positive outcomes or regulatory approval. We may experience delays in our trials, which could include enrollment delays. 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. We may be unsuccessful in developing partnerships with other companies or obtaining capital that would allow us to complete our clinical trials or further develop and/or fund any future studies or trials. To date, we have incurred operating losses since our inception, and our future success 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, 2016, 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.
Developing Treatments Where Galectin-3 Protein is Implicated in Disease Clinical Phase Studies With Galectin-3 Inhibitor (GR-MD-02) Combination Cancer Immunotherapy (topic of this presentation; supplemental information to January 7, 2018 Corporate Presentation) Investigator-initiated phase 1b clinical trial of GR-MD-02 in combination with KEYTRUDA in advanced melanoma and other malignancies Encouraging early data with 5 of 8 responders (2 CR and 3 PR) in advanced melanoma Primary Program is in NASH Cirrhosis First randomized clinical trial of any drug to demonstrate a clinically meaningful improvement in portal hypertension or important aspects of liver biopsy in patients with compensated NASH cirrhosis Psoriasis and atopic dermatitis Small open label studies show clinically significant effect demonstrating activity of drug in human disease
Combination Cancer Immunotherapy Development Program Summary The vast majority of human (& experimental animal) cancers have a large increase of galectin-3 protein Galectin-3 inhibits the immune system from killing cancer cells and has other effects that allows cancers to thrive and spread to other areas of the body GR-MD-02 is a glycopolymer (polysaccharide), considered a Nonbiological Complex Drug (NBCD) that binds to galectin-3 protein, has strong patent protection, and is administered intravenously GR-MD-02 has robust efficacy in pre-clinical cancer models when used with immunotherapy agents GR-MD-02 is well tolerated and safe in preclinical toxicology and clinical trials (2 P1, P2a and P2b), including when used in combination with the immunotherapy pembrolizumab (KEYTRUDA) Investigator-initiated phase 1b clinical trials of GR-MD-02 in combination with KEYTRUDA (and Yervoy) in advanced melanoma and other malignancies Encouraging early data in KEYTRUDA trial with 5 of 8 responders (2 Complete responders (CR) and 3 Partial responders (PR)) in advanced melanoma
Critical Collaboration with Providence Cancer Center The Earle A. Chiles Research Institute at Providence Portland Medical Center Established 1993 by Dr. Walter Urba, MD, PhD Internationally recognized team of scientists and clinicians with focus on cancer immunotherapy William L. Redmond, PhD Associate Member and Director of Immune Monitoring Laboratory Research focused on mechanisms regulating the efficacy of combination immunotherapy and reversing tumor-induced immune suppression Conducted pre-clinical work with GR-MD-02 Brendan D. Curti, MD Director of Biotherapy Clinical Program Principal Investigator of GR-MD-02 immunotherapy clinical trials
T Cell-Modulating Antibodies For Cancer Immunotherapy Multiple therapies have been developed, or are in development, that stimulate the immune system to treat cancer Recent effective classes of immunotherapies are those that stimulate T cells by blocking inhibitory inputs (blocking antibodies or checkpoint inhibitors) or stimulate T cells (agonist antibodies) Marketed drugs (red circle) Anti-CTLA-4 (ipilimumab; Yervoy) Anti-PD1 (pembrolizumab; KEYTRUDA) Anti-PD-L1 (nivolumab; Opdivo)
Galectin-3 and Cancer Rabinovich G, Nat Rev Immunol, 2009 Gal-3 effects on cancer cells, macrophages and T-cells in the tumor microenvironment Gal-3 is produced by both tumor cells and macrophages and has multiple effects, including Reducing T cell receptor signaling thereby blocking immune effects on tumor cells Promoting T-cell apoptosis (cell death) Promoting angiogenesis and metastasis of cancer cells Promoting macrophage M2 polarization, increasing chemotaxis to recruit more macrophages, and enhancing gal-3 secretion
The Galectin-3 Inhibitor GR-MD-02 Appears to Augment Anti-Tumor Activity of Cancer Immunotherapies aCTLA-4 aPD-1 aPD-L1 GR-MD-02 GR-MD-02 aOX40 A galectin-3 inhibitor such as GR-MD-02 theoretically would have synergistic effects with other immunotherapies Pre-clinical studies have shown positive effects on multiple tumors when GR-MD-02 was combined with: Checkpoint inhibitors: Anti-CTLA-4 (ipilimumab; Yervoy) Anti-PD1 (pembrolizumab; KEYTRUDA) Anti-PD-L1 (nivolumab; Opdivo) T-cell agonists Anti-OX40 (in development)
Pre-Clinical Summary: GR-MD-02 in combination with other immunotherapies, vaccines, and radiation therapy enhances efficacy in multiple tumor models GR-MD-02 boosts frequency and persistence of antigen-specific T cells in non-tumor bearing mice alone and in combination with anti-CTLA-4 GR-MD-02 in combination with anti-CTLA-4, anti-PD-L1, or anti-PD-1 reduces tumor size and enhances survival in multiple tumor models (melanoma, prostate, breast, sarcoma) GR-MD-02 in combination with the anti-OX40 immunotherapy agonist Improves survival and reduces lung metastases (4T1 breast cancer model) Improves survival in the MCA-205 sarcoma model in a CD8 T cell-dependent manner Reduces the frequency of suppressive cells (MDSC) in the tumor microenvironment Reduces vascular endothelial frequency within the tumor GR-MD-02 plus Lm-Her2 tumor vaccine augments expansion of tumor-specific CD8 T cells, increases tumor regression, and boosts tumor-free survival GR-MD-02 in combination with radiation therapy increases tumor regression and boosts tumor-free survival
Preclinical Data Example: GR-MD-02 plus anti-OX40 antibody reduces tumor growth and prolongs survival in MCA-205 sarcoma in mice The combination of GR-MD-02 with anti-OX40 markedly enhances effect on tumor growth of either agent alone The combination of GR-MD-02 with anti-OX40 statistically significantly enhances survival over either agent alone
Phase 1b Clinical Trials Conducted by Providence Cancer Center Galectin Inhibitor (GR-MD-02) plus Ipilimumab (Yervoy) in Patients With Metastatic Melanoma Trial initiated in 2015, enrolled 7 subjects with GR-MD-02 doses of 1 and 2 mg/kg There were no adverse events identified due to GR-MD-02 No notable changes in the peripheral immune signature Trial stopped due to changes in the standard of care for melanoma (Keytruda was approved and replaced the use of Yervoy in many patients) GR-MD-02 Plus Pembrolizumab (KEYTRUDA) in Patients with Metastatic Melanoma and Other Cancers (oral head & neck, non small cell lung cancer)--ONGOING
GR-MD-02 Plus Pembrolizumab (KEYTRUDA) 12 GR-MD-02 used in combination with a flat dose (200 mg) of pembrolizumab in the following patients: Metastatic melanoma with progression after other treatment including pembrolizumab alone Recurrent or metastatic HNSCC with progression after other treatment d1 d22 d43 d64 d85 Every 3 weeks GR-MD-02 2 mg/kg (5 patients; completed) 4 mg/kg (3 patients; completed) 8 mg/kg (10 patients; underway) Pembrolizumab Imaging (CT/MRI/PET) Immune cells and markers https://clinicaltrials.gov/ct2/show/NCT02575404?term=gr-md-02&rank=2
Pembrolizumab plus GR-MD-02 Patients: Cohorts 1 and 2 Cohort Diagnosis Gender Age Disease Sites Prior Treatments Response 1 Melanoma Male 76 Subcutaneous (SQ), lung Surgery/IL-2/RT/oncolytic virus/Yervoy PR 1 Melanoma Female 63 SQ, muscle, lymph node (LN) Interferon/Yervoy SD→PD 1 Melanoma Female 82 SQ, bone, LN Surgery, Radiation PD 1 Melanoma Male 62 Brain/bone/lung/SQ/LN/liver IL-2, Yervoy, Opdivo SD→PD 1 Melanoma Male 65 SQ, LN, lung Vemurafenib, Dabrafenib + Trametinib CR 1 H & N Cancer Male 55 LN Surgery SD→PD 2 Melanoma Female 70 LN, lung Surgery, IL-2, Radiation PR 2 Melanoma Male 83 Lung, pleura Surgery CR 2 Melanoma Male 37 LN Surgery PR SD=stable disease; PD=progressive disease; PR=partial response; CR=complete response
Clinical Results of GR-MD-02 plus Pembrolizumab (KEYTRUDA) Waterfall plot of best objective clinical response post treatment (RECIST 1.1) 14 * * Head and Neck CA Response rate of 62.5% in melanoma compares favorably to best response of KEYTRUDA alone of 33%
CT Scan Showing Resolution of a Large Intramuscular Melanoma Deposit Baseline Day 85 15
Multiple PET Scan-Detected Melanoma Deposits Resolved Baseline Day 169 16 Multiple tumors in legs All tumors resolved
Multiple PET Scan-Detected Melanoma Deposits Resolved Baseline Day 169 17 Multiple tumors throughout body (red arrows) All tumors resolved: normal contrast seen in heart, kidneys and bladder
CT Scan Showing Resolution of a Lung Melanoma Deposit Baseline Day 85
Extensive Laboratory Analysis of Immune Cells and Immune Molecules The immune monitoring laboratory at EACRI (Earle A. Chiles Research Institute) performs analysis of multiple type of immune cells and immune molecules in the blood and tumors of patients before, during, and after therapy This analysis suggests that responders to therapy appear to have higher baseline levels of activated T lymphocytes which may provide better targeting of patients likely to respond Measurement of Monocyte Derived Suppressor Cells (MDSC) suggests that these are decreased by combination therapy in patients who respond to therapy. This is an important and novel observation since MDSC cells impair the response of the immune system to tumors. The extensive immune monitoring of patients in this trial will help elucidate the mechanism of action of GR-MD-02 in combination with pembrolizumab and help to identify the patients who will most benefit from combination therapy
Addition of GR-MD-02 to Pembrolizumab Appears Safe and Well Tolerated Pembrolizumab has significant toxicities and adverse effects on patients In the patients treated thus far with the combination of GR-MD-02 and pembrolizumab, the Principal Investigator has documented that there have been no additional adverse events or toxicities attributed to GR-MD-02 over those that would be anticipated with pembrolizumab If this observation holds up in further patients, this would be a potential advantage of GR-MD-02 as a combination agent because most combination therapies with pembrolizumab that are currently used or being studied add significantly to the toxicity of the therapy
Summary: GR-MD-02 for Combination Cancer Immunotherapy Many combination approaches are under investigation using marketed and experimental cancer immunotherapy drugs As a galectin-3 inhibitor, GR-MD-02 represents a novel mechanism of action, differentiated from the many other drugs that are currently being tested As a combination agent, GR-MD-02 has a number of potential advantages Broad enhancement of anti tumor activity in pre-clinical studies with checkpoint inhibitors (e.g. anti PD-1/PD-L1), immuno-stimulatory agonists (e.g. aOX40), cancer vaccines, and radiation therapy Potential novel and unique markers of anti-cancer activity GR-MD-02 is safe and well tolerated and does not appear to increase adverse events when used in combination immunotherapy with pembrolizumab Cost of manufacture is relatively inexpensive when compared to biologics The third patient cohort treated with GR-MD-02 8 mg/kg, which will enroll at least 10 additional patients, is well underway with results anticipated in mid-2018