Immuron Limited Oral Immunoglobulins Changing the Paradigms of Care January 2018 ASX:IMC NASDAQ:IMRN

Transcription

1 Immuron Limited Oral Immunoglobulins Changing the Paradigms of Care January 2018 ASX:IMC NASDAQ:IMRN

2 Forward Looking Statement Certain statements made in this presentation are forward-looking statements and are based on Immuron s current expectations, estimates and projections. Words such as anticipates, expects, intends, plans, believes, seeks, estimates, guidance and similar expressions are intended to identify forward-looking statements. Although Immuron believes the forward-looking statements are based on reasonable assumptions, they are subject to certain risks and uncertainties, some of which are beyond Immuron s control, including those risks or uncertainties inherent in the process of both developing and commercializing technology. As a result, actual results could materially differ from those expressed or forecasted in the forward-looking statements. The forward-looking statements made in this presentation relate only to events as of the date on which the statements are made. Immuron will not undertake any obligation to release publicly any revisions or updates to these forwardlooking statements to reflect events, circumstances or unanticipated events occurring after the date of this presentation except as required by law or by any appropriate regulatory authority.

3 Company Highlights Clinical stage biopharmaceutical company targeting inflammatory-mediated and infectious diseases with oral immunotherapies Validated technology platform with one registered asset generating revenue 2 Lead clinical assets in Phase 2 development for the treatment of multiple high value indications, Fat Liver Disease and CDI. Excellent safety profile, GRAS by FDA, expedited regulatory review and approval process Well positioned to address high unmet medical need in multiple blockbuster markets High-value peer licensing deals and M&A underscore potential upside Company listed on NASDAQ in 2Q 2017 Experienced Management Team and strong support from leading KOLs and institutions (NIH, DoD) 3

4 Platform Overview: Oral Immunoglobulins 1 Vaccines Are Developed 2 Antibodies Are Harvested from Colostrum Antigen Specific Antibodies (IgG and IgG1) + Adjuvants Induction of regulatory T-cells + Clearance of Targeted GUT Pathogens 3 Broad Therapeutic Effect Reduced gut and blood pathogens responsible for initiating inflammation Reduces systemic inflammation Lowers organ injury Strong anti-toxin properties Decrease toxin levels results in decrease gut damage Generally Regarded as Safe (GRAS) Platform capable of producing multiple drug candidates Long-term value creation Competitive Advantage Bovine IgG possesses a unique ability to remain active in the human GI tract delivering its full benefits to the bacteria found there Bovine IgG is capable of withstanding the acidic environment of the stomach and is resistant to proteolysis by the digestive enzymes in the GI tract Safety established Not absorbed into the blood 4

5 Immunotherapy Targeting Pathogenic Bacteria Technology Platform Capable of Producing High Levels of Antibodies against specific pathogenic and antigenic determinants Targeting Virulence Factors; Spores Lipopolyscaccarride Endotoxins Exotoxins Fimbrae & Molecules which facilitate adhesion Surface Layer Proteins which contribute to Colonisation Antigens Important For; Outer Membrane Stability Host Immune Evasion Motility Host Cell Adherence Colonization Cellular Invasion Flagella (Flagellin) 5

6 Immunotherapy Targeting Pathogenic Bacteria Proprietary Technology to Weed Harmful Bacteria Direct Protective MOA Toxin Neutralization Suppression of Germination Suppression of Adhesion Suppression of Motility Suppression of Colonization Indirect Protective MOA Inhibition of Toxin Induced Inflammatory Signal Cascades Anti-Inflammatory Effect via Stimulation of the Innate Immune Response Enhancement of Gut Barrier Function Inhibition of Epithelial Cell Apoptosis 6

7 Immuron s Clinical Programs Multiple Near-Term Inflection Points Program Indications Development Stage Pre-Clinical Phase 1 Phase 2 Phase 3 Program Highlights Anti-Inflammatory Programs IMM-124E NASH - Interim data reported 2Q Topline results expected 1Q 2018 IMM-124E ASH - NIH Funded; UVA - Topline results expected 2019 IMM-124E Pediatric NAFLD - NIH Funded; Emory University - Topline results expected 4Q 2018 IMM-124E Colitis Collaboration with Dr. Rogler, Zurich University IMM-124E Autism Murdoch Childrens Research Institue, La Trobe & RMIT Universities Anti-Infective Programs IMM-529 C. difficile - Phase 1/2 initiated 4Q Topline results expected Q IMM-124E / Shigella Vaccine Shigella Infections Collaboration with US Army IMM-124E Campylobacter; ETEC Infections Collaboration with US Navy 7

8 TRAVELAN Hyperimmune bovine colostrum powder 200mg (30 caplets, 24 month shelf life) Reduces the risk of TD, reduces the symptoms of minor GI disorders Australian Packaging US Packaging Regulatory Authority Regulatory Pathway Indications TGA Listed Medicine Reduces the risk of travellers diarrhoea Reduces the symptoms of minor gastro-intestinal disorders Antimicrobial Medsafe (New Zealand) FDA (USA) Not marketed in New Zealand Self-affirmed generally regarded as safe (GRAS) Dietary supplement. FDA does not review dietary supplements for safety and effectiveness Not marketed in New Zealand Hyperimmune colostrum dietary supplement Health Canada Natural Health Product Travelan helps reduce the risk of traveller s diarrhea. EMA (Europe) Not marketed in Europe Not marketed in Europe ARTG Listing for Travelan 8

9 Novel Approaches Targeting Pathogenic Gut Bacteria Travelan contains high levels of specific antibodies which have been generated against 13 strains of Enterotoxigenic E.coli bacteria, the most common cause of Travellers Diarrhea. The active pharmaceutical ingredient is bovine colostrum powder enriched with anti-etec antibodies (> 35% w/w) scientifically proven to bind and remove LPS Bacteria and their LPS Toxin from the Digestive System. Travelan directly targets the pathogens in the gut that are implicated in Travellers Diarrhea and prevents the infection and its resulting symptoms from occurring in the first place. Travelan is a biological product which is intended to prevent Travellers Diarrhea without destroying the microbiome like antibiotics do, allowing the microbiome to return to a healthy state. 9

10 Novel Approaches Targeting Pathogenic Gut Bacteria Formulated with 13 Strains of E-Coli Serotype Strains # ETEC O6: H16 B2C ETEC O8: H19 C55 3/3c3 ETEC O15: H4 PE 595 ETEC O25: H42 E11881A ETEC O27: HR C ETEC O63: H- PE 673 ETEC O78: H11 H10407 ETEC O114: H21 E20738/0 ETEC O115: H- PE 724 ETEC O128: H21 EI 37-2 ETEC O148: H28 B7A ETEC O153: H12 E8772/0 ETEC O159: H- PE 768 Proven to Be Cross-Reactive (binds) to Other E-Coli Strains and Gram-Negative Bacteria ETEC strain M452C1 [serotype O20:H-] ETEC strain T0225-C4 [O75:H4] ETEC strain [O126:H-] ETEC strain G33 [O126:H12] ETEC strain M145C2 [O128:H(NT)] ETEC strain E23477/0/A [O139:H25] ETEC strain ND782 [O141:H4] ETEC strain ND748 [O149:H10] ETEC strain E11881A [O25:H42] Enterobacter aerogenes strain ATCC Enteropathogenic Escherichia coli strain E2348/69 Klebsiella pneumoniae strain ATCC 26 Pseudomonas aeruginosa strain ATCC Salmonella typhimurium strain ATCC Vibrio cholerae strain 6239 Yersinia enterocolitica strain 67R Citrobacter rodentium strain DSB100 Shigella flexnerii LPS 2a (CVD Lot # 2457T) Shigella sonnei LPS 53G (CVD Lot # 95-WRAIR), Shigella dysenterii LPS (CVD #1251), Salmonella enterica Serovar Typhi LPS (Difco # ), Salmonella enterica Serovar Typhimurium LPS (Sigma # L6511) Salmonella enterica Serovar Enteriditis LPS (Sigma # L2012)

11 Novel Approaches Targeting Pathogenic Gut Bacteria Significantly reduces adherence of CFA/I producing ETEC strains to a cell-line that mimics the human small intestinal epithelium Pre-Clinical Studies Significantly reduces the motility of ETEC strains through soft agar Binds to both the bacterial surface and flagella Has substantially greater reactivity against purified ETEC flagella antigen than IgG purified from non-immune colostrum powder Without Travelan : Bacteria attach to gut wall and infect With Travelan : Bacteria neutralized by Travelan antibodies 11

12 Novel Approaches Targeting Pathogenic Gut Bacteria Travelan has undergone clinical testing in two patient randomised, double-blind, placebo-controlled clinical trials (90 healthy volunteers) Clinical Studies Methodology: Study 1: 30 participants in total, 15 randomised to treatment and 15 to placebo Active treatment with Travelan 400mg with buffer tds against placebo Oral challenge with O78 ETEC strain (H10407), treatment 5 days after challenge with ciprofloxacin 500mg bd for 5 days Diarrhea was defined as passage of two or more unformed stools during 48 hour period within 72 hours of the challenge Results: Travelan provided 90.9% prophylactic efficacy against diarrhea (due to infection by the major strain of E.coli that causes TD) In addition these trials showed a significant reduction in abdominal cramps and stomach pain compared to those who did not receive Travelan. There were no reported treatment-related side effects. Otto et al RCTs using a tablet formulation of hyperimmune bovine colostrum to prevent diarrhea caused by ETEC in volunteers. Scandinavian Journal of Gastroenterology, 2011; 46: Clinical protocols were approved by Bioethics Committee of the Warsaw Chamber of Physicians. Procedures in accordance with Declaration of Helsinki. 12

13 IMM-124E Revolutionary Treatment for Fatty Liver Disease

14 NASH (Non-Alcoholic Fatty Liver) Pathophysiology NASH Pathophysiology Blood derived antigens (including circulating LPS) determines tolerance vs. inflammation Kupffer cells play a key role in liver inflammation and fibrosis Tregs hold a key role in tolerance (homeostasis) Much like hepatic tolerance the gut immune system can promote antiinflammatory effect Source: Adapted from Cohen-Naftaly; Scott L. Friedman,

15 IMM-124E in NASH (Non-Alcoholic Fatty Liver) IMM-124E Liver: Activated Kupffer Cells (F4/80 macrophages) Fibrosis and Inflammation Gut: Intestinal LPS Intestinal Permeability Tolerance Activation of Innate system to suppress inflammation (NKT, DC, macrophages) Serum: Insulin resistance Circulating LPS TGF-β TNF-α IL-2, IL-6, IL-10, IL-12 Treg (CD4, CD25, FoxP3) 15

16 IMM-124E: Fatty-Liver Portfolio 3 Phase II Trials Three Ongoing Phase 2 Programs: NASH, ASH and Pediatric NAFLD NASH ASH Lead Principal Investigator: Arun Sanyal; Former President of AASLD (American Association for the Study of Liver Diseases) and current Chair of the Liver Study Section at the NIH (National Institute of Health) Multi-center, double-blinded, placebo controlled trial; 25 sites running in US, Australia and Israel Fully recruited: 133 patients with biopsy proven NASH Primary endpoint: changes in liver fat content confirmed by MRI; changes in ALT (liver enzymes) 3 arms: placebo, high dose and low dose Timing: topline results by 1Q 2018 NIH funded; sponsored by University of Virginia Expected enrollment: 66 patients Endpoint: ALT Timing: topline results in 2019 Pediatric NAFLD NIH funded; sponsored by Emory University Expected enrollment: 40 patients Endpoint: ALT; 3 months treatment Timing: topline results in 4Q

17 IMM-124E Interim analysis Goal: Validate Safety and test for futility Analysis was not powered for efficacy due to sample size Design: interim analysis initiated when 80 patients reached 24W and have 2 MRI Execution: Performed by an independent Committee to keep Company Blinded Results: Excellent Safety Treatment well tolerated at both doses No Futility Significant change in ALT and AST at 24W Significant reduction in ALT and AST over time compared to placebo Dose response Non-absorbable 17

18 Phase II: Interim Analysis Report - Improves Liver Function Box plot Results for predicted of a Phase ALT AUC IIafrom clinical ANCOVA trial; (FAS N=133 population) 24 Week Treatment; Improved NO SAFETY Liver ISSUES Enzymes REPORTED Predicted value for ALT AUC Using logarithmic regression the predicted value was used Both 1200 mg and 600 mg arms demonstrated significant change over placebo (p= and p=0.0075) but were not different from one another (p=0.3589) Group 1200mg 600mg Placebo Predicted value adjusted for Baseline ALT 18

19 IMM-124E Key Milestones 3Q Q NASH Phase 2 interim analysis NASH Phase 2 Closed Results of MOA studies: - Duke - Sanyal Biotechnology NASH Phase 2 Topline Results Pediatric NAFLD Phase 2 topline results ASH Phase 2 topline results Results of colitis & US DoD pre-clinical studies: 2017/

20 IMM-529 Neutralizing Clostridium difficile, while Sparing the Microbiome

21 IMM-529 in Clostridium difficile Infection (CDI) Biologic with unique triple mechanism of action - Targets and neutralizes the toxin B, the spores and the vegetative cells Potential to redefine the standard-of-care (SOC) therapy for CDI - Stops virulence, without impacting the microbiome - Compelling data in all three phases of the disease including (1) prevention of primary disease, (2) treatment of primary disease and (3) prevention of recurrence - Orally administrated, safe >70% survival rate in CDI mice treated with IMM-529 vs. <7% survival rate in control groups Potential orphan disease designation; Potential breakthrough / fast track designations Market exclusivity (biologics; High barriers to generic biosimilar entry) 21

22 IMM-529 for the Treatment of CDI Market Opportunity Therapeutic market is expected to grow from US$356.3 million in 2014 to over $1.5 billion by 2024 CAGR 15% Nearly 30,000 patients die each year from C. difficile infections (US) Potential orphan disease (7 years market exclusivity and premium pricing) Unmet Need Vancomycin and metronidazole are the current standard of care, accounting for 80% of patient share (US) However, therapies are plagued by significant CDI recurrences (1st relapse: 25%; 2nd: 40%; 3rd: 50%) underscoring need for new treatments There is also growing resistance to vancomycin treatment IMM-529 Positioning Highly differentiated Neutralizes C. difficile but does not impact microbiome Only asset that targets not only toxin B but also the spores and the vegetative cells responsible for recurrence Can be used in combination with standard of care Targets many isolates Sources: GlobalData, Decision Resources, CDC 22

23 Triple Action MOA Neutralizing C. difficile; Sparing the Microbiome Spores Infectious Particles IMM-529 antibodies bind to multiple epitopes on surface antigens on spores and prevent adheres to host cells and limit germination. IMM-529 antibodies bind to multiple epitopes on the surface layer proteins (SLP) on vegetative cells and limit colonization. Vegetative Cells Heat, ethanol and UV resistant. Survive gastric acid, adhere to cells in the colon and germinate. Fimbriae and other surface layer proteins (SLP) contribute to bacterial colonization. Fimbriae are used to adhere to other bacteria and to host cells and is one of the primary mechanisms of virulence Toxin B IMM-529 antibodies bind to multiple epitopes effectively neutralize toxin B, inhibiting toxin mediated epithelial cell apoptosis and limit toxin translocation into the systemic circulation and inflammatory cascades. Toxin B is essential for virulence. Toxin B disrupt the cytoskeleton and tight junctions of intestinal epithelial cells. 23

24 IMM-529 antibodies are cross-reactive with the exosporium layer from C. difficile spores exosporium 250 kda Non-immune IMM-529 #1 IMM-529 #2 250 kda 250 kda 1 KI (A + B + ) 2 M7404 (A + B + ) 3 VPI10463 (A + B + ) 4 GE (A + B + ) 5 MDU2992 (A - B + ) 6 JGS6133 (A + B + ) 7 AI35 (A - B + ) (A - B + ) IMM-529 contains antibodies that are cross-reactive with the exosporium layer of spores from a variety of isolates (human and animal) Strain used to generate product

25 IMM-529 antibodies are crossreactive with Toxin B from different C. difficile strains Non-immune IMM-529 #1 IMM-529 #2 250 kda 250 kda 250 kda 1 KI (A + B + ) 2 M7404 (A + B + ) 3 VPI10463 (A + B + ) 4 GE (A + B + ) 5 MDU2992 (A - B + ) 6 JGS6133 (A + B + ) 7 AI35 (A - B + ) (A - B + ) 9CD37 (A - B - ) 10Purified Toxin B (commercial) IMM-529 contains antibodies specific to Toxin B from a variety of human and animal isolates

26 % c e ll d e a th % c e ll d e a th % c e ll d e a th IMM-529 antibodies neutralize Toxin B from historical and hypervirulent strains C o m m e r c ia l p u r ifie d T o x in B (s t ra in V P I ) H is to r ic a l T o x in B (s t ra in ) H y p e r v ir u le n t T o x in B (s t ra in K I) **** **** *** *** **** **** N o N o n -im m u n e IM M B 1 A n tib o d y 0 N o N o n -im m u n e IM M B 1 A n tib o d y 0 N o N o n -im m u n e IM M B 1 A n tib o d y

27 Relapse Studies P e rc e n t s u rv iv a l Treatment Studies P ercent survival Prevention Studies P ercent survival Results of Pre-Clinical Studies S u r v iv a l U n in fe c te d, N o tre a tm e n t In fe c te d, N o tre a tm e n t In fe c te d, N o n -im m u n e Ig G tre a tm e n t In fe c te d, IM M tre a tm e n t In fe c te d, V a n c o m y c in tr e a tm e n t Demonstrated ~70% survival rate without use of antibiotics vs. 0% for control group (P<0.0001) All studies statistically significant hours post infection S u r v iv a l U ninfected, No treatm ent In fe c te d, N o tre a tm e n t In fe c te d, N o n -im m u n e Ig G tre a tm e n t In fe c te d, IM M tre a tm e n t In fe c te d, V a n c o m y c in tr e a tm e n t Demonstrated ~80% survival rate without use of antibiotics vs. <7% in control group (P<0.0001) Potentially only therapeutic (approved or in development) that can treat all phases of the disease: D a y s p o s t in fe c tio n 1. Prophylaxis S u r v iv a l ** p= In fe c te d + S O C In fe c te d + S O C + IM M Demonstrated ~20% relapse rate vs. ~89% relapse rate in control group (P<0.0027) 2. Treatment 3. Recurrence D a y s a fte r v a n c o m y c in tre a tm e n t c e a s e d 27

28 Phase 1/2 Study Design Phase 1/2, randomized, double blind, placebo-controlled clinical study of IMM-529 for the treatment of CDI 60 subjects to be enrolled up to 3 weeks of definitive diagnosis of CDI (at least 20 subjects to be enrolled within the first 72 hours) Subjects randomized to IMM-529 or placebo in a 2:1 ratio Treatment duration: 28 days on top of SOC (vancomycin / metronidazole) Follow-up: 3 months overall Phase 1/2 Study in CDI Initiated 4Q 2017 Primary objective: To evaluate the safety and tolerability of IMM-529 together with standard of care (SOC) in patients with CDI Secondary objective: To evaluate the effectiveness of IMM-529 together with SOC to treat patients with CDI 28

29 IMM-529 Key Milestones 3Q/4Q Clinical supplies manufacturing Topline results expected from Phase 1/2 study in CDI Initiation of Phase 1/2 Trial in CDI 29

30 NASH and C. difficile Comps Indicate Potential for Substantial Growth Company Ticker Program Development Stage Market Cap* Program in NASH ICPT Obeticholic acid Phase 3 US$2.9B GNFT Elafibranor Phase 3 US$1.1B CNAT ENCORE-LF Phase 2 US$195M Program in C. Difficile MCRB SER-109; SER-262 Phase 2 US$423M SMMT SMT19969 Phase 1 US$143M *As of May 4, 2017 ASMB ABI-M101 Preclinical US$419M 30

31 Capital Profile Immuron Limited (ASX:IMC NASDAQ:IMRN) Current Top 10 Shareholders Rank Holder Name Current Qty % 1 HSBC CUSTODY NOM AUST LTD (ADR Program) 19,531, % 2 * GRANDLODGE PL 9,056, % 3 AUTHENTICS AUST PL 8,624, % 4 RETZOS EXECUTIVE PL 3,800, % 5 * ANASTASIOU PETER + K P 2,907, % 6 INVERAREY PL 2,731, % 7 * FIFTY-FIFTH LEPRECHAUN PL 2,645, % 8 INSYNC INV PL 2,500, % 9 SBI INV PR LLC 2,000, % 10 ADVANCE PUBLICITY PL 2,000, % TOTAL TOP 20 SHAREHOLDERS 55,798, % BALANCE OF SHARES 74,642, % TOTAL SHARE ON ISSUE 130,440, % * Denotes a Director Related Entity Current Company Market Capitalization AUD$22.3M USD$19.1M (21 st Dec 2017) 31

32 Travelan OTC/Business A unique OTC targeting Traveler s Diarrhea Travelan/OTC: Unique value proposition that is valued by consumers and customers - Significantly reduces the motility of ETEC strains - Binds to multiple epitopes and antigens on both the bacterial surface and flagella - Has substantially greater reactivity against purified ETEC flagella antigen than IgG purified from nonimmune colostrum powder Annual Revenues of AU$1M+; Cash flow positive - Net revenues: 1H % vs 1H Pursuing new geographies - Potential WW peak sales: $20M+ Multiple ways to keep growing OTC business: - Continued penetration of current markets - Geographic expansions - New products / New formulations (e.g., shigella) 32

33 Key Milestones Expected to Drive Value 2Q Q Q IMM Clinical supplies manufacturing IMM-124E - NASH Phase 2 interim analyses Results from colitis preclinical studies and US Army and US Navy trials expected 2017/2018 IMM-124E - NASH Phase 2 study closed - NASH MOA IMM Initiation of Phase 1/2 Trial in CDI IMM-124E - NASH Phase 2 topline results - NASH centric transaction - Pediatric NAFLD Phase 2 topline results - ASH Phase 2 topline results IMM Topline results expected from Phase 1/2 study in CDI 33

34 Thank You