Corporate Presentation

Transcription

1 Corporate Presentation February 8, 2016 NASDAQ: GALT Galectin Therapeutics Inc.

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 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 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 further develop and/or fund any studies or trials. We are currently the subject of litigation, which may impact our human and capital resources. 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, 2014, 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 Galectin Therapeutics NASDAQ:GALT 2

3 Company Thesis Therapy for unmet medical need that may benefit a large number of people: Fatty liver disease (NASH) with advanced fibrosis/cirrhosis Novel protein target (galectin-3) and drug compound (GR-MD-02) Strong pre-clinical and early clinical data Competitive positioning with near- and mid-term Phase 2 clinical data Platform for multiple diseases Experienced team that can execute plan 2016 Galectin Therapeutics NASDAQ: GALT 3

4 Focused Developing Drugs For Major Unmet Medical Needs 45% of U.S. deaths estimated to be associated with fibrotic disease 1 Organ Fibrosis Lead indication is liver fibrosis/cirrhosis due to fatty liver disease (75% of all liver disease in U.S. 2 ) Potentially applicable to other fibrotic diseases based on pre-clinical studies Two Phase 2 clinical trials ongoing Other Potential Indications Combination cancer immunotherapy for advanced melanoma; two investigator initiated clinical trials Moderate-to-severe plaque psoriasis; Phase 2a exploratory trial ongoing 1 Wynn, TA. Nat Rev Immunol. 2004;4: doi: /nri Younossi, et al. Clin. Gasto. Hepatol. 2011;9: Galectin Therapeutics NASDAQ:GALT 4

5 Drugs That Target Galectin-3 Protein May Address These Unmet Medical Needs Galectin-3 Protein Interactions between sugar-containing proteins Modulates cell signaling and immune cell function Role in Disease Increased in inflammation and fibrogenesis Critical in liver, lung, kidney and heart fibrosis High levels in majority of cancers Lead Drug Candidate GR-MD-02 Carbohydrate drug that disrupts gal-3 function Extensive analytical analysis using state-of-the-art methods to support human use Strong patent portfolio Efficacy in preclinical models with encouraging human results 2016 Galectin Therapeutics NASDAQ:GALT 5

6 Pipeline of Indications for GR-MD-02 Clinical Focus Stage of Development Drug Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Fibrosis GR-MD-02 NASH cirrhosis NASH advanced fibrosis Lung, Kidney, Cardiovascular fibrosis Cancer Immunotherapy (combination therapy) GR-MD-02 + Yervoy GR-MD-02 + Keytruda Melanoma Melanoma Plaque Psoriasis (exploratory) GR-MD-02 Moderate-severe New Galectin-3 Inhibitors Discovery program to identify subcutaneous and oral drugs 2016 Galectin Therapeutics NASDAQ:GALT 6

7 Lead Indication in Organ Fibrosis ADVANCED FIBROSIS AND CIRRHOSIS DUE TO FATTY LIVER DISEASE NASH: (NON-ALCOHOLIC STEATOHEPATITIS) 2016 Galectin Therapeutics NASDAQ:GALT 7

8 NASH Is An Epidemic With No Approved Drug Therapy NASH is a chronic inflammatory disease of the liver that leads to progressive scar formation (fibrosis) Major global problem driven by increasing obesity & diabetes Affects survival and causes need for liver transplants Very large number of individuals affected million with NASH in US 1-2 million in US with NASH cirrhosis, the most advanced disease U.S. market could be $25 Billion by 2025 Global market could be $35-40 Billion by Who will be the kings of NASH-ville? Key players and an overview. May 21, 2015, Alethia Young, Deutsche Bank Markets Research 2016 Galectin Therapeutics NASDAQ: GALT 8

9 Scarring (Fibrosis) Of The Liver In Advanced NASH Leads To Patient Morbidity and Mortality Early Disease (low stage fibrosis) Late Disease (advanced fibrosis) Fibrosis Progression Stage 1 Stage 2 Stage 3 Stage 4 Liver biopsy (Blue = fibrosis) Cirrhosis No increased mortality* Increased mortality* *All cause mortality as compared to reference group with prospective follow-up of up to 33 years (Ekstedt, et al. Hepatology 2015;61: ) 2015 Galectin Therapeutics NASDAQ:GALT 9

10 Galectin Therapeutics Is Targeting Late-Stage NASH Which Narrows the Competition in the Disease Area Phase 2/3 Companies with drugs in development for NASH Early Disease (low stage fibrosis) Late Disease (advanced fibrosis) Stage 1 Stage 2 Stage 3 Stage 4 (Cirrhosis) Phase 3 Intercept Genfit (announced) Phase 2 Tobira Conatus Galmed Cempra Duract Others Phase 2 Galectin Gilead Phase 2* Galectin Gilead *Conatus also has program targeting cirrhosis, but it is mixed etiologies, not only NASH 2016 Galectin Therapeutics NASDAQ:GALT 10

11 Why can GR-MD-02 be used in advanced fibrosis? Because it can reverse NASH, fibrosis, and cirrhosis in preclinical models Mouse model of NASH Reduces inflammation, fat, and cell death Prevents as well as reverses fibrosis Targets macrophages and reduces galectin-3 Peer-reviewed publication: Traber PG and Zomer E. Therapy of Experimental NASH and Fibrosis with Galectin Inhibitors. PLOS ONE 2013;8:e83481 Rat model of liver fibrosis/cirrhosis Reduces inflammation and cell death Reverses fibrosis and cirrhosis Reduces portal hypertension associated with cirrhosis Targets macrophages and reduces galectin-3 Peer-reviewed publication Traber PG, Chou H, Zomer E, Hong F, Klyosov A Fiel M-I, Friedman, SL. Therapy of Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLOS ONE 2013;8:e Galectin Therapeutics NASDAQ: GALT 11

12 GR-MD-02 Reversed Cirrhosis In Rat Model Toxin induced cirrhosis in rats Toxin continued during GR-MD-02 treatment Vehicle-Treated (control) GR-MD-02-Treated (4 weekly doses) Reduces portal pressure which correlates with primary endpoint in cirrhosis trial 2016 Galectin Therapeutics NASDAQ:GALT 12

13 Successful Phase 1 Trial In NASH Patients With Advanced Fibrosis Fast Track designation from FDA Four dose, double-blind, placebo-controlled, dose escalation trial in NASH patients with advanced fibrosis GR-MD-02 was safe and well tolerated Reached targeted doses without adverse effects Highest dose tested may have an effect on liver fibrosis Reduced FibroTest, a composite test of 5 serum markers Serum alpha-2 macroglobulin, a component of the FibroTest accounted for the reduction Reduced liver stiffness assessed by FibroScan 2016 Galectin Therapeutics NASDAQ:GALT 13

14 Statistically Significant Reduction In Alpha-2 Macroglobulin (A2M) Serum Levels Seen At The 8 mg/kg Dose A2M is involved in fibrogenesis and correlates to degree of liver fibrosis ns 4 Legend and Notes: ns 3 4 th dose + 14 da Cohort 1 2 mg/kg 4 th dose + 3 da Cohort 2 4 mg/kg p < p < p < nd dose 4 th dose 4 th dose + 3 da + 14 da Cohort 3 8 mg/kg 1. Mean ± standard deviation 2. Placebo values were combined for all three cohorts because there were no differences (n=19 separate data points) 3. Not significant versus placebo, two-sided t-test (n=6) 4. Not significant versus placebo, two-sided t-test (n=7) 5. Significant for three groups versus placebo, ANOVA with Dunnett s test for multiple comparisons (n=7) 2016 Galectin Therapeutics NASDAQ:GALT 14

15 Evidence Of Reduced FibroScan Scores In Cohort 3 Patients Treated With GR-MD-02 3 of 5 patients treated with GR-MD-02 had reduction in liver stiffness to below 80% of baseline values (red squares)* Placebo GR-MD-02 (8 mg/kg) 120% 80% *FS added during cohort 2, but only available at most centers for cohort 3. In cohort 3 there were technically adequate scans at baseline, Day 38 and Day 63 in 5 patients administered GR-MD-02 and 3 patients administered placebo. Five patients in cohort 3 were not available for FibroScan analysis (3 placebo and 2 active) because of unavailability of the instrument at the site (1 placebo and 1 active), unavailability of the appropriate instrument probe (1 active), a technically inadequate baseline scan (1 placebo), and the Day 63 scan not being performed (1 placebo) Galectin Therapeutics NASDAQ:GALT 15

16 Phase 2 Clinical Trials Underway (Details in Appendix) Indication Objective Expectation From Successful Study NASH-FX NASH with Advanced Fibrosis (Stage 3) 4 Months of Therapy Reduction of liver fibrosis as assessed using 3 non-invasive tests Reduction in fibrosis Basis for future Phase 2b or Phase 3 trials 30 patients, 15 placebo and 15 active Enrollment will complete Q Primary endpoint: LiverMultiScan (multi-parametric MRI) Secondary endpoints: MR-elastography, FibroScan Top line data report September Galectin Therapeutics NASDAQ:GALT 16

17 Non-Invasive Assessments Of Liver Fibrosis In NASH-FX Trial Normal LiverMultiScan* MR-Elastography Transient Elastography (FibroScan ) Transducter Probe Ribs Vibrator Cirrhosis Whole liver assessment of fibrosis using multi-parametric magnetic resonance imaging *Perspectum Diagnostics Banerjee, et al. J. Hepatol. 2014;60:69-77 Whole liver assessment of stiffness using magnetic resonance imaging with mechanical pulse Regional assessment of liver for tissue stiffness (FDA approved) Echosense 2016 Galectin Therapeutics NASDAQ:GALT 17

18 Phase 2 Clinical Trials Underway (Details in Appendix) Indication Objective Expectation From Successful Study NASH-CX NASH with Cirrhosis (Stage 4) 1 Year of Therapy Reduction of portal pressure and liver fibrosis Reversal or improvement of cirrhosis Has potential to be a pivotal trial 156 patients, 50 U.S. sites, three arms (placebo, 2 drug) Primary endpoint: Portal pressure (HVPG) Secondary: Liver biopsy, FibroScan, methacetin breath test, serum biomarkers, and clinical progression Enrollment on track to report top line data end of Galectin Therapeutics NASDAQ:GALT 18

19 Important NASH Milestones: Top Line Data Expectations* Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Stage 3 Fibrosis Galectin (NASH-FX) Gilead (Simtuzimab) Stage 4 (Cirrhosis) Galectin (NASH-CX) Gilead (Simtuzimab) GR-MD-02 and simtuzimab have different mechanism of action Simtuzimab has failed in two fibrosis indications (myelofibrosis and lung fibrosis) If both work, combination therapy is possible Early NASH (Stage 1, 2, 3) Intercept (P3): Primary completion date October 2021 Genfit (P3 ready) not announced Tobira (P2): June 2016 Galmed (P2): End 2016 *Estimated from clinicaltrials.gov and analyst reports Conatus (P2): 1H Galectin Therapeutics NASDAQ:GALT 19

20 NASH Advanced Fibrosis Program with GR-MD-02: Summary Unmet medical need with a very large potential market Competitively well positioned in NASH with advanced fibrosis and cirrhosis Reversal of fibrosis/cirrhosis in preclinical models In human Phase 1, GR-MD-02 is safe and well tolerated with evidence of potential effect on fibrosis Phase 2 clinical trials address two different patient populations with near- and mid-term timing of results 2016 Galectin Therapeutics NASDAQ: GALT 20

21 Potential as a Platform Technology for other Diseases Cancer Skin inflammatory disease: psoriasis Other areas of organ fibrosis where positive effects have been shown with GR-MD-02 in preclinical studies Lung fibrosis Kidney fibrosis Heart and vascular fibrosis 2016 Galectin Therapeutics NASDAQ: GALT 21

22 Lead Indication in Cancer Immunotherapy ADVANCED MELANOMA 2016 Galectin Therapeutics NASDAQ:GALT 22

23 Cancer Immunotherapy Opportunity Focus on Immunotherapy Galectin-3 plays an important role in reducing the ability of immune system to fight cancer Advanced Melanoma as Initial Indication Even with newly approved drugs, a substantial unmet medical need remains Providence Cancer Center, Portland Oregon Critical Collaboration Established Performed preclinical studies showing efficacy of GR-MD-02 with checkpoint inhibitors Conducting and funding clinical trials *Siegel, et al. CA Cancer J Clin 2012;62: Galectin Therapeutics NASDAQ:GALT 23

24 Potential Sites Of Action For Galectin Inhibition In Tumor Immunology Immunotherapies Checkpoint Inhibitor Blockage: anti-ctla4 anti-pd1 + Clonal Expansion CD8+ T-Cells Galectin-3 Tumor Cells Galectin-3 T-Cells CD8+ T-Cells Cytokines (kill tumor cells) Potential for galectin inhibitors to enhance anti-tumor immune response Potential for galectin inhibitors to enhance antitumor activity of T-cells 2016 Galectin Therapeutics NASDAQ:GALT 24

25 Checkpoint Inhibitors Plus GR-MD-02 Boosts Anti- Tumor Immunity, Reduces Tumor Size And Increases Survival In Mouse Cancer Models These data are on TC-1 prostate cancer cells (also effective in breast cancer, melanoma, and sarcoma) *p<0.05 actla-4 = anti-ctla-4 mab [ipilimumab in humans (Yervoy, BMS)] apd-1 = anti-pd-1 mab [pembrolizumab in humans (KEYTRUDA ) Merck] Unpublished data 2013: Stefanie N. Linch, Melissa J. Kasiewicz, Peter G. Traber, and William L. Redmond, Galectin Therapeutics and Earle A. Chiles Research Institute (EACRI), Portland Oregon 2016 Galectin Therapeutics NASDAQ:GALT 25

26 Investigator Initiated Trials: Melanoma Patients With Advanced Melanoma Using GR-MD-02 In Combination With Yervoy Advanced melanoma with indication for Yervoy treatment Dose escalation with GR-MD-02 plus standard Yervoy Measure tumor and immune system response Two dosing groups complete showing no dose-limiting toxicity Patients With Advanced Melanoma Using GR-MD-02 In Combination With KEYTRUDA Melanoma progression after Yervoy and/or BRAF targeted therapy Melanoma progression after KEYTRUDA monotherapy Remainder of design mirrors first study Trial initiated in Q4 2015, enrollment to begin Q Study details on clinicaltrials.gov 2016 Galectin Therapeutics NASDAQ:GALT 26

27 Summary of Cancer Immunotherapy Program Collaboration with investigative group at PPMC who have significant expertise in basic tumor immunology and translational clinical trials Preclinical studies demonstrate in multiple cancers that GR-MD- 02 augments the anti-tumor effects of monoclonal antibody checkpoint inhibitors Initial target is advanced melanoma, but also applicable to other cancer types Two Phase 1b clinical trials funded by Providence Cancer Center May get early evidence of effect since advanced immune response markers being used to evaluate drug effect in addition to tumor response 2016 Galectin Therapeutics NASDAQ: GALT 27

28 Exploratory Indication: Moderate-to-Severe Psoriasis Patient in Phase 1 trial had apparent remission Galectin-3 plays important role in skin and there is increase in skin vessels of patients with psoriasis 1,2 Open-label, single-site, 10-patient, 3 months of therapy Data report in September 2016 If efficacious, there may be market potential because drug appears safe, is low cost, and the one patient who responded had long-term benefit 1 Larsen L, et al. J. Derm Sci. 2011;64: Lacina L, et al. Folia Biologica. 2006;52: Galectin Therapeutics NASDAQ: GALT 28

29 Expected Development Program Milestones Advanced Liver Fibrosis/Cirrhosis Study Indication Endpoints Start Data Reporting GT-026 NASH-CX GT-028 NASH-FX Advanced Melanoma Study Indication Endpoints Start Data Reporting Phase 1b: Yervoy Phase 1b: KEYTRUDA Psoriasis NASH with cirrhosis NASH with advanced fibrosis Advanced melanoma Advanced melanoma Portal pressure (HVPG); liver biopsy Multi-parametric MRI Comparisons include MRE and FibroScan Safety ir-recist Immune markers Safety ir-recist Immune markers Underway End 2017 Underway End Q Underway: under direction of Providence Underway; enrollment Q Dose Group 1: complete Dose Group 2: complete Dose Group 3: enrolling Study Indication Endpoints Start Data Reporting Phase 2a: GT-030 Moderate-to-severe plaque psoriasis Psoriasis Activity Severity Index (PASI 75) TBD Underway End Q Galectin Therapeutics NASDAQ:GALT 29

30 Experienced Executive Leadership Team Marc Rubin, M.D. Chairman of the Board Peter G. Traber, M.D. President, CEO, CMO Harold H. Shlevin, Ph.D. COO Corporate Secretary Jack W. Callicutt CFO 2016 Galectin Therapeutics NASDAQ:GALT 30

31 Program Summary Lead drug (GR-MD-02) targets liver fibrosis associated with NASH (non alcoholic steatohepatitis) Unmet medical need with a very large potential global market Targeting late-stage NASH, with advanced fibrosis/cirrhosis, which is desirable from regulatory and commercial perspectives Preclinical studies with GR-MD-02 indicated positive effects on multiple aspects of NASH, including fibrosis reversal Completed Phase 1 studies demonstrated drug was safe and well tolerated and provided proof-of-concept on anti-fibrotic activity Currently engaged in two Phase 2 NASH clinical trials in cirrhosis and advanced fibrosis without Cirrhosis NASH with advanced fibrosis (NASH-FX) with data readout in 2016 NASH cirrhosis (NASH-CX) with data readout in 2017 Investigator-initiated studies in cancer immunotherapy and psoriasis enhance the GR-MD-02 opportunity 2015 Galectin Therapeutics NASDAQ: GALT 31

32 Information for Prospective Investors Strong risk--reward investment thesis Easily accessible, in depth information on clinical development programs: Newsweek feature article: online now and in print on Feb Galectin Therapeutics NASDAQ: GALT 32

33 APPENDIX 2014 Galectin Therapeutics NASDAQ:GALT 33

34 The NASH-CX Trial (GT-026) Design Fibrosis Portal Pressure Complications Morbidity and Mortality CRO: PPD Sites: U.S only Underway Top line: End 2017 Primary Endpoint: Reduction of hepatic venous pressure gradient (HVPG) as a measure of portal pressure compared to placebo at 1 year of treatment Secondary Endpoints: At least one stage change in histopathological fibrosis stage Liver collagen on liver biopsy (digital morphometric analysis) Liver stiffness as determined by FibroScan Score Metabolic capacity of the liver as determined by 13 C methacetin breath test Progression of cirrhosis as determined by complications show/nct ?term=g R-MD-02&rank= Galectin Therapeutics NASDAQ:GALT 34

35 The NASH-FX Trial (GT-028) Design Reduction of liver fibrosis as assessed using three non-invasive tests Primary Endpoint: Difference between placebo and GR-MD-02 in the baseline adjusted mean change in liver fibrosis as measured by corrected T1 (ct1) mapping as determined from LiverMultiScan (LMS), a multi-parametric MRI protocol. Secondary Endpoints: Baseline-adjusted change in magnetic resonance elastography (as measured in kpa) Baseline-adjusted change in FibroScan Score (as measured in kpa) Galectin Therapeutics NASDAQ:GALT 35