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FibroScan will be performed at baseline and after the four doses in as many patients as possible to gain experience with this method of fibrosis assessment. Results from Cohort 2 are expected to be reported in July August 2014 time frame. Planning for phase 2 clinical trials is ongoing. The results of the first cohort suggest that 2 mg/kg is a safe, well tolerated dose that has indication of anti fibrotic and anti inflammatory effect.
Clinical Biochemistry 2011 2 Weigert, et al. J Clin Endocrinol Metab, 2010 Summary of Findings GR MD 02 was safe and well tolerated at 2 mg/kg (80 mg/m 2 ) with no drug related adverse events Pharmacokinetics was consistent between individuals and after single and multiple doses; exposure was 40% of lowest dose used in NASH animal model; this was a therapeutic dose Key composite biomarkers of fibrosis improved after four doses of GR MD 02 Key inflammatory cytokines were decreased after four doses of GR MD 02 Patients with greater cellular injury as indicated by elevated ALT levels, had a marked decrease in CK 18, a cell death biomarker Galectin 3 blood levels do not correlate with disease activity and are not a biomarker of drug effect in patients with NASH with advanced fibrosis In addition to being safe and well tolerated, GR MD 02 improved biomarkers of fibrosis, inflammation and liver cell injury in patients with NASH with advanced fibrosis 30 2014 Galectin Therapeutics | NASDAQ:GALT Next Steps: Continuation of Phase 1 Trial 2014 Galectin Therapeutics | NASDAQ:GALT 31 The dose of GR MD 02 will be increased to 4 mg/kg (160 mg/m 2 ) in the second cohort of 8 10 patients Eight clinical sites in the US are now active to facilitate rapid enrollment of cohort 2 FibroScan , a FDA approved ultrasonic measure of liver tissue elasticity, has been added to the protocol for cohort 2.
Aliment. Pharmacol. Ther, 2007 Exploratory cytokines were not elevated and/or did not change including INF , Endothelin 1, IP 10, VEGF, CD40 ligand Markedly Elevated Alanine Aminotransferase (ALT) Levels Decreased With GR MD 02 Treatment 2014 Galectin Therapeutics | NASDAQ:GALT 23 Typical for NASH patients, there was a broad range of baseline ALT levels Those with ALT levels below 50 U/L had no change with therapy Two patients with ALT above 100 U/L, both of whom received active drug, had reductions of 39 U/L and 67 U/L One patient with ALT between 50 and 100 had minimal reduction of 10 U/L 100 200 (2 patients) 50 100 (1 patient) 0 50 (5 patients) Cell Death Biomarker CK18 Was Reduced In Two Patients With Highest ALT Levels 2014 Galectin Therapeutics | NASDAQ:GALT 24 CK 18 (M65) ALT CK 18, a biomarker of cell death of hepatocytes, was markedly reduced in the two patients with ALT greater than 100 U/L Fibrosis Biomarkers Were Reduced In The Two Patients Receiving GR MD 02 With Highest ALT* 2014 Galectin Therapeutics | NASDAQ:GALT 25 Lumican ALT FibroTest FibroTest scores were markedly decreased in the high ALT patients after treatment with GR MD 02 Lumican, a matrix protein that is involved in fibrogenesis in the liver, was elevated in all patients, but was highest and had the greatest decrease with treatment in the two patients with high ALT levels Patient with intermediate ALT not included in analysis because of false negative FibroTest score Patients With Low ALT Levels Receiving GR MD 02 Had Improvement In Fibrosis Markers But Not Cell Death Markers 2014 Galectin Therapeutics | NASDAQ:GALT 26 ALT FibroTest CK 18 (M65) Lumican The three GR MD 02 treated patients with low ALT levels did not have changes in ALT These three patients had lower CK 18 levels which did not decrease with therapy Fibrosis markers of FibroTest and Lumican did improve with treatment GR MD 02 Treatment Appears To Improve Both Major Pathological Processes In NASH 2014 Galectin Therapeutics | NASDAQ:GALT 27 Improvement in Fibrosis Biomarkers: There was a statistically significant reduction in Fibrotest and trends towards a reduction in ELF score and hyaluronic acid Improvement in Inflammation Biomarkers: There were statistically significant reductions in IL 6, IL 8 and TNF a, all important cytokines in NASH Improvement in Cell Death Biomarkers: A patient subset with high ALT levels indicative of more cellular injury had improvement in CK 18 Steato Hepatitis (NASH Activity) Ballooning of liver cells (cell death/apoptosis) key hallmark Fat in liver cells (steatosis) Immune cell infiltration (inflammation) Fibrosis/Cirrhosis Increase in collagen/matrix Disruption of architecture Liver cell nodules Patients Had A Normal Range Of Blood Galectin 3 Levels At Baseline And No Change With Treatment 2014 Galectin Therapeutics | NASDAQ:GALT 28 Timing of gal 3 levels Before 1 st infusion 28 day after 1 st infusion 14 days after 4 th infusion Cohort Range Normal Range** Gal 3 (ng/mL) 13.2 to 25.2 5.4 to 26.2 *Baseline values **Range of values in a non diseased population published by manufacturer (BG Medicine) Blood and Tissue Levels Of Galectin 3 Are Not Correlated In Mouse NASH Model Nor Human NASH 2014 Galectin Therapeutics | NASDAQ:GALT 29 Marked changes in expression of galectin 3 in liver macrophages are not reflected in changes in blood galectin 3 Liver Gal 3 Staining Blood Level Liver Tissue Level Normal NASH No evidence for correlation between blood galectin 3 levels and disease activity or fibrosis stage in patients with NASH 1 Blood galectin 3 levels in humans are correlated with obesity 1,2 and diabetes 2 1 Yilmax, et al.
Aliment. Pharmacol. Ther. 2007 Interleukin 6 Levels Were Significantly Reduced In GR MD 02 Treated Patients 2014 Galectin Therapeutics | NASDAQ:GALT 22 Pro Inflammatory cytokine secreted by T cells and macrophages. Increased serum levels in NASH Levels not increased in patients GR MD 02 treated patients had significant reduction when compared to placebo Study Cohort* NAFLD** Obese Controls** IL 6 pg/mL 6.1 2.5 23.1 72.9 7.6 6.3 *Baseline levels **Jarrar, et al.
Aliment. Pharmacol. Ther. 2007 2014 Galectin Therapeutics | NASDAQ:GALT 21 TNF Levels Were Significantly Reduced In GR MD 02 Treated Patients Pro Inflammatory cytokine and promotes lipid accumulation Elevated serum levels in NASH Study patients had elevated serum levels GR MD 02 treated patients had significant reduction when compared to placebo Study Cohort* NAFLD** Obese Controls** TNF pg/mL 23 5.8 6.0 16.6 1.9 0.3 *Baseline levels **Jarrar, et al.
Patient had high haptoglobin which is known for false negative test. FibroTest has been shown to: Correlate with stage of fibrosis Assess fibrosis regression Assess fibrosis progression Predict liver related mortality Note: While the numbers are small, exploratory statistics have been performed to evaluate differences using a one sided t test and confirmed using a non parametric test, Mann Whitney ELF Score Tended To Decrease In GR MD 02 Treated Patients 2014 Galectin Therapeutics | NASDAQ:GALT 17 7.7 9.8 Severe Fibrosis Moderate Fibrosis Mild/No Fibrosis 10.1 8.8 Siemens Diagnostics Equivalent to a 0.5 change on scale ELF score has been shown to: Correlate with stage of fibrosis Assess progression (0.032 increase/yr in PBC) Predict mortality (a one unit change in score correlates to a 2 fold change in liver related mortality) 11.5 Hyaluronic Acid (HA) Levels Were Decreased In A Subset Of Patients On GR MD 02 2014 Galectin Therapeutics | NASDAQ:GALT 18 3 of 6 patients treated with GR MD 02 had significant reductions in HA No change in placebo patients Multiple clinical studies have shown that HA levels correlate with liver fibrosis HA levels measured in NASH mice treated with GR MD 02 HA levels decreased at all three doses compared to vehicle treated controls Some animals had variable levels Animal Study Study Results No consistent elevation and/or changes in Osteopontin, TGF or MMPs; Lumican presented in later slides Serum Biomarkers of NASH Inflammation and Injury 2014 Galectin Therapeutics | NASDAQ:GALT 19 Cellular Injury Serum Transaminases ALT and AST Enzymes released from liver cells 2/3 of NASH patients have normal levels at any given time Entire spectrum of disease can be seen with normal levels Cytokeratin 18 A circulating biomarker of cell death Predictive of NASH severity Cell Death (Apoptosis) Key cytokines IL 6 IL 8 TNF Exploratory** INF Endothelin 1 IP 10 VEGF CD40 ligand Inflammatory Cytokines * Evidence of association with human NASH and importance in pathogenesis, particularly as products of macrophages ** Some evidence of association with human and/or animal NASH in at least one publication For more information and references on biomarkers: http://bit.ly/1jzFK50 Interleukin 8 Levels Were Significantly Reduced In GR MD 02 Treated Patients 2014 Galectin Therapeutics | NASDAQ:GALT 20 Pro inflammatory cytokine expressed in macrophages Elevated serum levels in NASH Study patients had elevated serum levels GR MD 02 treated patients had significant reduction when compared to placebo Study Cohort* NAFLD** Obese Controls** IL 8 pg/mL 28.0 8.6 24.1 38.5 7.8 3.6 *Baseline levels **Jarrar, et al.
Gastro. 2005 Major Pathological Processes in NASH 2014 Galectin Therapeutics | NASDAQ:GALT 14 Steato Hepatitis (NASH Activity) Ballooning of liver cells (cell death/apoptosis) key hallmark Fat in liver cells (steatosis) Immune cell infiltration (inflammation) Fibrosis/Cirrhosis Increase in collagen/matrix Disruption of architecture Liver cell nodules Do Not Always Correlate in Same Patient Can have high NASH activity score with minimal fibrosis Can have advanced fibrosis/cirrhosis with minimal NASH activity We measured biomarkers of both major pathological processes Serum Biomarkers Of Fibrosis In NASH 2014 Galectin Therapeutics | NASDAQ:GALT 15 Composite Scores FibroTest (FibroSURE ) Indirect biomarker of fibrosis Age and gender, Alpha 2 macroglobulin, Haptoglobin, Apolipoprotein A1, GGTP, Total bilirubin Individual Markers Exploratory* TGF Lumican Osteopontin Matrix Metalloproteinases ELF (Enhanced Liver Fibrosis) Score Direct biomarker of fibrosis Hyaluronic acid TIMP1 (tissue inhibitor of metalloproteinase 1) P3NP (amino terminal propeptide of type III pro collagen) Hyaluronic Acid Matrix polysaccharide Direct marker Correlates to fibrosis * Indicates that there is some evidence that suggests they are increased in fibrosis, but not confirmed in sufficient number of patients or studies For more information and references on biomarkers: http://bit.ly/1jzFK50 FibroTest (FibroSURE ) Scores Significantly Decreased In GR MD 02 Treated Patients 2014 Galectin Therapeutics | NASDAQ:GALT 16 Equivalent to a 10% change on scale **One patient on GR MD 02 had scores 0.08 which was highly discordant with biopsy (stage 3).
HepQuant ) Labeled substrate WHVP FHVP Time (s) Vibrator Probe Ribs Transducter Serum markers Liver biopsy Transient Elastography (FibroScan ) Hepatic venous pressure gradient (HVPG) Source: Nat Rev Gastroenterol Hepatol. 2010 Aug;7(8):425 36.Epub 2010 Jun 29. MR Elastography Potential serious complications 1/50,000 th of liver High sampling variability 41% discordance of 1 fibrosis stage in NASH* *Ratziu, et al.
Last subject, last blood draw was 3 7 14; Last subject, last visit was 3 21 14 11 2014 Galectin Therapeutics | NASDAQ:GALT Patient Safety There were no Serious Adverse Events There were no Treatment Emergent Adverse Events in patients receiving GR MD 02 that were attributed to the drug One patient receiving GR MD 02 had several mild AE s that were judged by investigator to be unrelated to drug Two patients receiving placebo had mild AE s that were judged by investigator as possibly related There were no treatment emergent laboratory or ECG findings GR MD 02 at a dose of 2 mg/kg (80 mg/m 2 ) was safe and well tolerated Pharmacokinetics: GR MD 02 Blood Levels Were Consistent Between Individuals And Not Significantly Different After Single Or Multiple Infusions 2014 Galectin Therapeutics | NASDAQ:GALT 12 First Infusion (week 1) Fourth Infusion (week 7) The AUC in humans given 2 mg/kg was approximately 40% of the AUC of the lowest therapeutic dose in the mouse NASH model C max = 16.3 g/mL T 1/2 = 19.9 h AUC = 572.6 h* g/mL V ss = 5.2 L Variability 15% C max = 17.7 g/mL T 1/2 = 20.5 h AUC = 645.4 h* g/mL V ss = 4.7 L Variability 24% Mean GR MD 02 Plasma Concentration Time Profiles of 6 Patients on Weeks 1 and 7 Accumulation ratio ~1.16 (95% CI 0.85 to 1.47) Assessment Methods for Liver Fibrosis 2014 Galectin Therapeutics | NASDAQ:GALT 13 Functional metabolic and shunt tests (eg.
Primary endpoints: Safety Pharmacokinetics Secondary endpoints: Disease related serum biomarkers to assess for potential treatment effect Patient Characteristics Safety Patient Characteristics 6 women and 2 men Ages 40 64 (mean=54) Mean body mass index (BMI)=39 (obese 30) Diabetes Mellitus in 6 patients Patients had a liver biopsy within one year of enrollment All patients had definitive pathological diagnosis of NASH 7 patients had stage 3 fibrosis (bridging); 1 patient had stage 4 fibrosis All patients enrolled completed full protocol through final follow up visit at day 70.
The combination would increase rate of resolution. + Collagen Degradation +/ GR MD 02 Is Being Developed For The Indication Of NASH With Advanced Fibrosis (Stage 3 and 4) 9 2014 Galectin Therapeutics | NASDAQ:GALT Obesity/Insulin Resistance/Diabetes Steatosis (fatty liver) NASH (inflammation, cell death) Stage 1 2 3 Fibrosis Stage 4 Cirrhosis No certainty of progression from early to late disease in an individual Late disease much closer to clinical outcomes Surrogates of clinical outcomes are better developed for late disease GR MD 02 reduces inflammation, ballooning and fat in NASH and reduces existing fibrosis and reverses cirrhosis in animal models Early Disease Late Disease Clinical Outcomes Complications Transplant Death Targeting Late Disease Phase 1 Clinical Trial Of GR MD 02 In NASH With Advanced Fibrosis: Report On Cohort 1 2014 Galectin Therapeutics | NASDAQ:GALT 10 0 28 35 42 56 70 Day Infusion 1 Biomarkers Biomarkers Patient inclusion: Biopsy proven NASH with advanced fibrosis (stage 3) Design : Cohort has 8 patients (6 active, 2 placebo, blinded) Dose: Starting dose of 2 mg/kg lean body weight (equivalent to 80 mg/m 2 ); Infusions at days 0, 28, 35 and 42.
Liver Fibrotic Tissue Homeostasis Normal In the normal liver, collagen and matrix protein synthesis matches degradation to provide appropriate amount of extracellular matrix. Collagen Synthesis Collagen Degradation = Collagen Synthesis Collagen Degradation Fibrosis Collagen Synthesis Fibrosis can resolve either by a reduction in collagen synthesis or an increase in degradation.
For a discussion of additional factors impacting our business, see our Annual Report on Form 10 K for the year ended December 31, 2013, and our subsequent filings with the SEC. You should not place undue reliance on forward looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward looking statements. 2 2014 Galectin Therapeutics | NASDAQ:GALT Our Pipeline Of Galectin 3 Inhibitors 2014 Galectin Therapeutics | NASDAQ:GALT 3 Clinical Focus Stage of Development Drug Indication Discovery Pre clinical Phase 1 Phase 2 Phase 3 Fibrosis GR MD 02 Fatty liver disease with advanced fibrosis Lung fibrosis Kidney fibrosis Cancer Immunotherapy GR MD 02 Melanoma Galectin 3 Inhibitors GR MD 03 Subcutaneous GR MD 04 Oral G XXX* Oral Report on first cohort of Phase 1 Clinical Trial *Galectin Sciences, LLC Timely Reporting: Last bloods: 3 7 14 Last visit: 3 21 14 Summary of Findings GR MD 02 was safe and well tolerated at 2 mg/kg (80 mg/m 2 ) with no drug related adverse events Pharmacokinetics was consistent between individuals and after single and multiple doses; exposure was 40% of lowest dose used in NASH animal model; this was a therapeutic dose Key composite biomarkers of fibrosis improved after four doses of GR MD 02 Key inflammatory cytokines were decreased after four doses of GR MD 02 Patients with greater cellular injury as indicated by elevated ALT levels, had a marked decrease in CK 18, a cell death biomarker Galectin 3 blood levels do not correlate with disease activity and are not a biomarker of drug effect in patients with NASH with advanced fibrosis In addition to being safe and well tolerated, GR MD 02 improved biomarkers of fibrosis, inflammation and liver cell injury in patients with NASH with advanced fibrosis 4 2014 Galectin Therapeutics | NASDAQ:GALT All Chronic Liver Diseases Lead To Fibrosis Example: Liver Fibrosis In Fatty Liver Disease (NASH) 2014 Galectin Therapeutics | NASDAQ:GALT 5 Stage 1 Stage 2 Stage 3 Stage 4 Patient Liver biopsy Healthy Fatty Fibrosis Cirrhosis Liver failure Bleeding Encephalopathy Edema Asymptomatic Only therapy for patients with cirrhosis is liver transplantation Bridging Fibrosis Cirrhosis Portal/Central Pericellular/Central (High Mag) Blue=fibrosis Occurs over decades Galectin 3 is Expressed In Liver Macrophages And Is Markedly Increased In Human and Mouse NASH 2014 Galectin Therapeutics | NASDAQ:GALT 6 Normal Mouse Liver NASH Mouse Liver Kupffer cells= liver resident macrophages Portal macs=macrophages located in portal regions Immunohistochemistry for Gal 3 (brown pigment indicates gal 3) NASH Human Liver GR MD 02, A Galectin 3 Inhibitor, Has Therapeutic Effect On NASH With Fibrosis In Mouse Model 2014 Galectin Therapeutics | NASDAQ:GALT 7 Normal NASH:Control NASH:GR MD 02 GR MD 02 Effects NAFLD Activity Score Fat Cell death Inflammation Collagen (Fibrosis) Galectin 3 Protein Improvement is linked to decreased tissue Galectin 3 H E Sirius Red Gal 3 GR MD 02 Is A Galectin 3 Inhibitor That Reduces Collagen Synthesis And Increases Collagen Degradation In Pre Clinical Models 2014 Galectin Therapeutics | NASDAQ:GALT 8 Restoration to Normal Fibrosis results from increased collagen and other matrix protein synthesis with little to no change in collagen degradation.
Regardless of the results of current or future studies, we may be unsuccessful in developing partnerships with other companies or obtaining capital that would allow us to further develop and/or fund any studies or trials. To date, we have incurred operating losses since our inception, and our ability to successfully develop and market drugs may be impacted by our ability to manage costs and finance our continuing operations.
We may experience delays in the current trial, and we may have difficulty enrolling patients and processing the resulting data. Future phases or future clinical studies may not begin or produce positive results in a timely fashion, if at all, and could prove time consuming and costly. Plans regarding development, approval and marketing of any of our drugs are subject to change at any time based on the changing needs of our company as determined by management and regulatory agencies.
Factors that could cause our actual performance to differ materially from those discussed in the forward looking statements include, among others, that results from the first cohort of Phase 1 may differ materially from future results, and there is no guarantee that the current clinical trial will lead to positive outcomes or that GR MD 02 will ever be approved by the FDA.
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 GR MD 02 and expectations regarding the clinical trial, including the future enrollment of patients and the timing of results from the second cohort.
GT 020 Phase 1 Clinical Trial: Results of First Cohort Release: March 31, 2014 Webcast: April 1, 2014 NASDAQ: GALT www.galectintherapeutics.com 2014 Galectin Therapeutics inc. Exhibit 99.1 Forward Looking Statement This presentation contains, in addition to historical information, forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
Therefore, this defines at least one potential dose level for phase 2 clinical trials.