SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
PURSUANT TO SECTION 13 OR 15(d)
OF THE SECURITIES EXCHANGE ACT OF 1934
Date of Report (Date of earliest event reported): April 16, 2018
GALECTIN THERAPEUTICS INC.
(Exact name of registrant as specified in its charter)
|(State or Other Jurisdiction
4960 PEACHTREE INDUSTRIAL BOULEVARD, Ste 240
NORCROSS, GA 30071
(Address of principal executive office) (zip code)
Registrants telephone number, including area code: (678) 620-3186
(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 April 16, 2018, Galectin Therapeutics Inc. (the Company) posted to its website a presentation of results of its NASH-CX clinical trial 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 8 OTHER ITEMS
|Item 8.01||Other Items.|
On April 16, 2018, the Company issued the press release attached hereto as Exhibit 99.2.
SECTION 9 FINANCIAL STATEMENTS AND EXHIBITS
|Item 9.01||Financial Statements and Exhibits.|
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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: April 16, 2018||By:|
|Jack W. Callicutt|
|Chief Financial Officer|
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A multicenter, randomized, double-blind, placebo-controlled trial of Galectin-3 inhibitor (GR-MD-02) for one year in patients with NASH cirrhosis and portal hypertension The NASH-CX Trial 1Naga Chalasani, 2Guadalupe Garcia-Tsao, 3Zachary Goodman, 4Eric Lawitz, 5Manal Abdelmalek, 6Mary Rinella, 7Michael Ryan, 8Mazen Noureddin, 9Christopher Jue, 1Maxmillan Pyko, 10Adam Allgood, 10Harold Shlevin, 10Rex Horton, 10Eliezer Zomer, 10Peter G. Traber, 11Rohit Loomba, 12Brent Neuschwander-Tetri, 13Arun Sanyal, 14Stephen A Harrison 1Indiana University, Indianapolis, IN, 2Yale University, New Haven, CT, 3INOVA Fairfax Hospital, Fairfax, VA, 4Texas Liver Institute, San Antonio, TX, 5Duke University, Durham, NC, 6Northwestern University, Chicago, IL, 7Digestive and Liver Disease Specialists, Norfolk, VA, 8Cedars Sinai Medical Center, Los Angeles, CA, 9Digestive Health Specialists, Winston-Salem, NC, 10Galectin Therapeutics, Norcross, GA, 11UCSD, San Diego, CA, 12St. Louis University, St. Louis, MO, 13VCU, Richmond, VA, 14Pinnacle Clinical Research, San Antonio, TX Exhibit 99.1
Rationale for Galectin-3 Inhibition in NASH Gal-3 is a lectin protein that binds to galactose residues on glycoproteins and is increased in NASH and liver fibrosis/cirrhosis Gal-3 null mice are resistant to NASH and fibrosis Gal-3 Stellate Cell Macrophage Myofibroblast Macrophage Subsets Hepatocyte Scavenger Receptor + + + 1 Traber PG and Zomer E.PLOS ONE 2013;8:e83481 2 Traber PG, Chou H, Zomer E, Hong F, Klyosov A Fiel M-I, Friedman, SL. PLOS ONE 2013;8:e75361. Gal-3 involved in multiple pathophysiologic processes in NASH and liver fibrosis GR-MD-02 is a complex carbohydrate drug that inhibits gal-3 and improves pathology of NASH and reverses fibrosis/cirrhosis in animal models 1,2 Safe and well tolerated in normal and NASH patients with advanced fibrosis in Phase 1 studies
NASH-CX Clinical Trial Design NASH cirrhosis (biopsy) HVPG ≥ 6 mmHg Major Inclusion Criteria No decompensating event No or small varices Every other week intravenous infusion X 26 Placebo (PLB) GR-MD-02 2 mg/kg (GR2) GR-MD-02 8 mg/kg (GR8) Week 1 Week 54 n = 54 n = 54 n = 54 AIM: Evaluate Safety and Efficacy of GR-MD-02 in Compensated NASH Cirrhosis
Study Endpoints & Assessment Methods Primary Endpoint Change in Hepatic Venous Pressure Gradient (HVPG) Baseline and Week 54 Standardized Procedure and Central Blinded Reading Secondary Endpoints Change in Liver Histology NAFLD Activity Score and Fibrosis Staging Quantitative Morphometry for Collagen Baseline and week 54 Central Blinded Reading Endoscopy to Evaluate for Varices Complications of Cirrhosis
Study Disposition (36 US Sites) N = 290 Patients Screened N = 128 Screening Failures N = 162 Patients Randomized N = 54 Placebo (PLB) N = 53 2 mg/kg GR-MD-02 (GR2) N = 54 8 mg/kg GR-MD-02 (GR8) (1 withdrew before 1st dose) No Varices = 81 Discontinued Treatment = 3 Discontinued Treatment = 1 Discontinued Treatment = 6 Lost to Follow-Up (1) Withdrew consent (1) Physician decision (1) Adverse Event (1) Adverse Event (3) Lost to Follow-Up (2) Physician decision (1)
Study Demographics & Baseline Assessments Total (n=162) Placebo (n=54) GR2 (n=54) GR8 (n=54) Age, years; median (IQR) 59 (52, 65) 59 (53, 64) 60 (53, 65) 58 (51, 63) Female, n (%) 113 (70) 36 (67) 34 (63) 43 (79) Non-Hispanic White, n (%) 132 (81) 46 (85) 46 (85) 40 (74) BMI, kg/m2; median (IQR) 34 (31, 39) 34 (30, 38) 36 (31, 41) 35 (31, 38) Diabetes, n (%) 100 (62) 32 (59) 32 (59) 36 (67) AST (U/L) mean ± SD 49.8 ± 33.8 51.9 ± 48.2 48.3 ± 23.0 49.3 ± 24.8 ALT (U/L) mean ± SD 47.1 ± 34.1 48.1 ± 38.1 42.4 ± 21.0 50.9 ± 40.1 ELF Score mean ± SD 10.7 ± 1.2 10.8 ± 1.1 10.7 ± 1.2 10.7 ± 1.2 NAFLD Activity Score 4.2 ± 1.6 4.2 ± 1.5 4.3 ±1.3 4.2 ± 1.6 Ishak Stage (5/6) 48/123 13/41 20/43 15/39 Collagen (%) mean ± SD 10.5 ± 6.1 10.8 ±6.5 9.7 ± 5.9 11.0 ± 6.1 IQR=interquartile range; BMI=body mass index; AST=aspartate transaminase; ALT=alanine transaminase; ELF=enhanced liver fibrosis; NAFLD=non-alcoholic fatty liver disease
Baseline HVPG (mmHg) in Patient Groups There were no statistical differences between the three treatment groups for any of the measures. CSPH=clinically significant portal hypertension (≥ 10 mm Hg). MPH=mild portal hypertension (≥ 6 and < 10 mm Hg). Total Mean ± SD (n) Placebo Mean ± SD (n) GR2 Mean ± SD (n) GR8 Mean ± SD (n) Full Analysis Set 12.2 ± 4.2 (162) 11.6 ± 4.0 (54) 12.4 ± 4.3 (54) 12.7 ± 4.2 (54) CSPH Sub-group 14.3 ± 3.4 (108) 14 ± 3.1 (33) 14.2 ± 3.9 (37) 14.8 ± 3.1 (38) MPH Sub-Group 7.9 ± 1.2 (53) 7.8 ± 1.3 (21) 8.2 ± 1.0 (16) 7.8 ± 1.3 (16) No Varices Sub-Group 10.6 ± 3.5 (81) 10.8 ± 3.8 (33) 10.3 ± 2.9 (25) 10.7 ± 3.8 (23) With Varices Sub-Group 13.9 ± 4.2 (80) 12.9 ± 4.1 (21) 14.2 ± 4.6 (28) 14.2 ± 3.9 (31)
HVPG Primary Endpoint (Pre-Specified Analyses) mean ± SEM Mild Portal Hypertension mean ± SEM Total Patient Population ITT with LOCF (last observation carried forward); ANOVA with LSD (least squared difference) mean ± SEM
No Esophageal Varices at Baseline (Post Hoc Analysis) mean ± SEM ITT with LOCF; ANOVA with LSD 50% of patients (81) did not have varices at baseline
Responder Analysis (Post Hoc Analysis) Percentage of Patients Who Had a Clinically Relevant Reduction in HVPG With: ≥ 2 mmHg Decrease From Baseline AND ≥ 20% Decrease From Baseline Chi Square Analysis
PK-PD Correlation Between Human and Mouse Data 1Traber, P.G. and E. Zomer, Therapy of experimental NASH and fibrosis with galectin inhibitors. PLoS. One, 2013. 8(12): p. e83481. AUC of patients in NASH-CX (µg*hr./mL)
Change in HVPG Using PK Range Groups for GR8 mean ± SEM ITT; ANOVA with LSD; AUC=area under concentration curve (µg*hr./mL)
Changes in Liver Histology in Total Patient Population Trend towards improvement in NAS that did not reach significance No differences in steatosis across the treatment groups Statistically significant difference between GR2 and placebo for inflammation scores in the patients without baseline varices There was no effect on fibrosis staging or percent collagen on morphometry ITT Analysis Set; Ordinal logistic regression analysis mean ± SEM Statistically significant improvement in hepatocyte ballooning in GR2 group and trend in GR8 group
Correlation of Liver Biopsy Findings in HVPG Responders 1p value compared to placebo Ordinal logistic regression analysis was used to compare groups. ITT analysis set. GR21 GR81 Hepatocyte Ballooning 0.04 0.05 NAFLD Activity Score 0.19 0.28 Ishak Stage 0.20 0.59 Total Patient Population
Fewer Patients in GR Groups Developed New Varices Chi Square Analysis
Development of Cirrhosis Complications1 Total PLB GR2 GR8 FAS Population n=161 n=54 n=53 n=54 Complications – n(%) 21 (13) 9 (17) 5 (9) 7 (13) No-Varices Population n=81 n=33 n=25 n=23 Complications – n(%) 12 (15) 7 (21) 3 (12) 2 (9) MPH Population n=53 n=21 n=16 n=16 Complications – n(%) 4 (8) 3 (14) 1 (6) 0 Development of new varices ↑ CTP score ≥ 2 Variceal hemorrhage↑ MELD to ≥ 15 Clinically significant ascitesLiver transplantation or death Overt hepatic encephalopathy 1
Adverse Events Total (n=161) PLB (n=54) GR2 (n=53) GR8 (n=54) Treatment Emergent (TE) AEs 1323 431 509 383 Patients with at least ≥ grade 3 AE (%) 33 (20.5) 11 (20.4) 11 (20.8) 11 (20.4) Patients with at least 1 TE SAE1 (total) 25 (34) 8 (10) 5 (10) 12 (14) Study drug discontinued due to AE 3 0 0 32 Death 1 0 13 0 1 Two treatment emergent SAEs were rated by PI as possibly related to study drug (transient ischemic attack and worsening of hyponatremia, both GR8) but were rated by sponsor as unrelated; All other SAEs were unrelated to study drug 2 Probably related to drug: spasmodic cough (1); Unrelated to study drug: esophageal variceal bleeding (2). 3 Pulmonary embolism following hernia repair surgery, judged to be unrelated to study drug
Conclusions Change in HVPG associated with GR treatment was not significant in total patient population, but statistically significant in the pre-specified group of mild portal hypertension In patients without varices at baseline, there was a statistically significant difference in the GR2 group in the change in HVPG, percentage of responders, and development of new varices GR treatment improved hepatocyte ballooning in the total, which correlated with an improvement in HVPG Less pronounced effects of GR8 may be explained by its variable pharmacokinetics GR 2 and GR 8 treatment was well-tolerated with no safety signals These results warrant further trials with GR-MD-02 in compensated NASH cirrhotic patients without esophageal varices or those with mild portal hypertension
Acknowledgements We extend our thanks to the patients, their families and all participating investigators This study was funded by Galectin Therapeutics, Inc.
Galectin Therapeutics Late-Breaker Presentation at The International Liver Congress Reinforces and Extends the Positive Effects of GR-MD-02 in Patients With NASH Cirrhosis
NORCROSS, Ga. (April 16, 2018) Galectin Therapeutics Inc. (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins, today provided highlights from a late-breaker oral presentation at The International Liver CongressTM 2018, European Association for the Study of the Liver (EASL) in Paris, France on Saturday, April 14, 2018.
Naga P. Chalasani, M.D., Associate Dean for Clinical Research; Director, Division of Gastroenterology and Hepatology at Indiana University School of Medicine; and co-lead principal investigator on Galectin Therapeutics recent Phase 2b NASH-CX trial, delivered a late-breaker presentation entitled A multicenter, randomized, double-blind, PLB-controlled trial of Galectin-3 inhibitor (GR-MD-02) in patients with NASH cirrhosis and portal hypertension (click for presentation). The session focused on the Companys recent Phase 2b NASH-CX trial results and the innovative work the Company is doing for patients with non-alcoholic steatohepatitis (NASH) cirrhosis and portal hypertension.
Dr. Chalasanis late-breaker presentation highlighted and extended the studys primary findings in patients without esophageal varices and those with mild portal hypertension. Most importantly, in patients with NASH cirrhosis without esophageal varices, Galectin Therapeutics lead compound, GR-MD-02, demonstrated a statistically significant improvement in portal pressure, an improvement in liver cell death (hepatocyte ballooning) on biopsy for the total population, and a reduction in the development of new esophageal varices at the end of the one-year study. This subgroup is large and commercially relevant as it comprises about half of all patients with NASH cirrhosis.
Since reporting these initial findings in December 2017, continued analysis of the data has led to two additional findings that reinforce the positive effects of GR-MD-02. First, a statistically significant (p=0.04) correlation was identified between the decrease in portal pressure (HVPG, or hepatic venous pressure gradient) and the improvement in hepatocyte ballooning (viz., representing a decrease in liver cell death) upon treatment with GR-MD-02 at 2 mg/Kg. This suggests an important pathophysiological link between the improvement in liver biopsy and reductions in HVPG. To our knowledge, this is the first time that such a correlation has been demonstrated in a human clinical trial in patients with NASH cirrhosis.
Secondly, an evaluation of GR-MD-02 blood levels provided an explanation for the reduced efficacy response observed in the higher GR8 (8 mg/Kg) dose group. In the GR2 (2 mg/Kg) dose group, the blood levels (or total exposure to the drug as measured by area under the concentration-time curve) were tightly grouped. In contrast, there was a broad distribution of higher drug exposures in the GR8 group. Approximately half of the patients who received GR8 had GR-MD-02 blood concentration levels that had risen to a range where a reduced efficacy effect in the liver had been noted at very high doses in the NASH animal models.
When the GR8 group was divided, based on pharmacokinetic analysis of drug levels, into separate low (<12K µg*hr./mL) and high (>12K µg*hr./mL) drug exposure ranges, a statistically significant effect (p=0.03) of GR8 on both HVPG and hepatocyte ballooning was observed in those patients with drug levels in the lower drug exposure range. There was no corresponding statistically significant effect in the higher drug exposure range group of patients receiving GR8 in analogy to what was observed in the NASH animal studies. Therefore, the GR8 dose, in cirrhotic patients, seems to be at the upper range of efficacy. Importantly, this not only provides an explanation of the dose ranging results, but also more clearly defines the upper range of human drug dosing for GR-MD-02 in patients with NASH cirrhosis. Further, these results suggest it might be useful to explore intermediate doses between 2mg/kg and 8mg/Kg in future clinical studies.
The findings presented by Dr. Chalasani reinforce how the NASH-CX trial has demonstrated clinically meaningful improvement for those patients with NASH cirrhosis without esophageal varices with a drug that was well tolerated over one year of therapy, said Dr. Peter Traber, CEO and Chief Medical Officer of Galectin Therapeutics. Since about 50 percent of the total population of patients with NASH cirrhosis do not have esophageal varices and endoscopy to evaluate for varices is part of the standard of care for patients with NASH cirrhosis, there is a large and easily identifiable population of patients that might benefit from GR-MD-02. We look forward to presenting our findings to the FDA next month and to continuing advanced clinical studies to progress GR-MD-02 toward approval for the treatment of NASH cirrhosis in an appropriate patient group.
About NASH Cirrhosis
NASH cirrhosis is the final stage in the progression of non-alcoholic steatohepatitis (NASH), a disease of the liver which affects millions of people in the U.S. and worldwide. The liver cell death and inflammation seen in NASH eventually causes progressive scarring of the liver, that eventually can result in liver cirrhosis. While the early stages of NASH can be treated by changes in lifestyle, such as losing weight and exercising, once the disease progresses to NASH cirrhosis there is no treatment available short of a liver transplant. Of the total number of individuals in the world felt to presently have NASH, it is predicted that NASH cirrhosis will eventually kill 20 million of those people.
One of the results of NASH cirrhosis is an increase in blood pressure in the portal vein that brings blood and nutrients from the digestive tract through the liver and then out to the rest of the body. As the scarring effect of cirrhosis on the liver progresses, blood flow through the liver becomes more difficult,
increasing the blood pressure in the portal vein, creating varying degrees of portal hypertension. Eventually, this increase in blood pressure causes the veins connected to the liver to dilate and form esophageal varices, in which are dilated veins that divert blood through the esophagus, bypassing flow through the liver. These dilated veins in the esophagus are prone to bleeding, which is a major cause of morbidity and mortality in patients with NASH cirrhosis.
About the NASH-CX Trial
The NASH-CX trial was a randomized, double-blind, placebo-controlled Phase 2b clinical trial which enrolled 162 NASH cirrhosis patients; NASH-cirrhosis was confirmed both by liver biopsy and by confirmation of an elevated hepatic venous pressure gradient (HVPG). Enrolled patients received either 8 mg/kg or 2 mg/kg of GR-MD-02 or placebo every other week for 52 weeks, for a total of 26 doses. The aim of the NASH-CX clinical trial was to evaluate the safety and efficacy of GR-MD-02 in patients with well-compensated NASH cirrhosis. The primary study endpoint was a reduction in HVPG. Patients treated with GR-MD-02 were evaluated to determine the change in HVPG as compared to patients treated with placebo. Secondary end-points include NASH fibrosis stage and percent of fibrotic tissue based on liver biopsy and other non-invasive measures (see: www.clinicaltrials.gov for further details).
GR-MD-02 is a non-biologic complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of fatty liver disease and fibrosis. Galectin-3 plays a major role in diseases that involve scarring of organs including fibrotic disorders of the liver, lung, kidney, heart and vascular system. The drug binds to galectin-3 proteins and disrupts its function. Preclinical data in animals have shown that GR-MD-02 has robust treatment effects in reversing liver fibrosis and cirrhosis.
About Galectin Therapeutics
Galectin Therapeutics is dedicated to developing novel therapies to improve the lives of patients with chronic liver and skin diseases and cancer. Galectins lead drug (GR-MD-02) is a carbohydrate-based drug that inhibits the galectin-3 protein that is directly involved in multiple inflammatory, fibrotic, and malignant diseases. The lead development program is in non-alcoholic steatohepatitis (NASH) with cirrhosis, the most advanced form of NASH related fibrosis. This is the most common liver disease and one of the largest drug development opportunities available today. Additional development programs are for treatment of severe atopic dermatitis, moderate-to-severe plaque psoriasis, and in combination immunotherapy for advanced melanoma and other malignancies. Galectin seeks to leverage extensive scientific and development expertise as well as established relationships with external sources to achieve cost-effective and efficient development. Additional information is available at www.galectintherapeutics.com.
Forward looking statements
This press release contains 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
managements current expectations and are subject to factors and uncertainties that could cause actual results to differ materially from those described in the statements. These statements include those regarding the hope that Galectins development program for GR-MD-02 will lead to the first therapy for the treatment of NASH with cirrhosis, and those regarding the hope that our lead compounds will be successful in connection with the treatment of skin disease and cancer immunotherapy. Factors that could cause actual performance to differ materially from those discussed in the forward-looking statements include, among others, that Galectin may not be successful in developing effective treatments and/or obtaining the requisite approvals for the use of GR-MD-02 or any of its other drugs in development; the Companys future clinical studies may not 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 Galectins drugs are subject to change at any time based on the changing needs of the Company as determined by management and regulatory agencies; the Company may find that its patents does not offer the protection anticipated, and regardless of the results of any of its development programs, Galectin may be unsuccessful in developing partnerships with other companies or raising additional capital that would allow it to further develop and/or fund any studies or trials. Galectin has incurred operating losses since inception, and its ability to successfully develop and market drugs may be impacted by its ability to manage costs and finance continuing operations. For a discussion of additional factors impacting Galectins business, see the Companys Annual Report on Form 10-K for the year ended December 31, 2017, and subsequent filings with the SEC. You should not place undue reliance on forward-looking statements. Although subsequent events may cause its views to change, management disclaims any obligation to update forward-looking statements.
Galectin Therapeutics, Inc.
Jack Callicutt, Chief Financial Officer
Leigh Minnier, Vice President