HEART HEALTH: A NEW ROLE FOR PROBIOTICS

Transcription

1 HEART HEALTH: A NEW ROLE FOR PROBIOTICS Introduction to Cardioviva 1

2 Contents Heart Disease, Probiotics and the Microbiome ProSelect Discovery Process Cardioviva Basics Cardioviva Mechanism, Clinical Trials, Safety Why Recommend Cardioviva About Micropharma Limited 2

3 Heart Disease Facts By 2030, approximately 23.6 million people worldwide will die from cardiovascular disease (CVD). High blood cholesterol is one of the major risk factors for heart disease. The higher the blood cholesterol level, the greater the risk for developing heart disease or having a heart attack. 3

4 Probiotics and the Microbiome Scientific and public health leaders from around the world are putting significant effort into better understanding the microbiome, and its role and impact on human health. Probiotics (live healthy bacteria that confer a health benefit to the host) are being studied to determine if through the gut, they may have a role in improving specific health markers to maintain and improve health and wellness. Emerging science is evaluating whether the microbiome, and gut bacteria specifically, can play a role in health and certain chronic diseases such as heart disease. Certain probiotics are being investigated today for their ability to lower cholesterol. 4

5 Probiotics and Micropharma Micropharma Limited, a pioneer in the development of innovative and effective probiotics, is launching a portfolio of natural supplements and food ingredient solutions aimed at addressing specific health markers to help maintain and improve health and wellness. Cardioviva is the only probiotic that has been shown to help reduce total cholesterol and LDL-cholesterol levels in hypercholesterolemic adults, through the microbiome in the gut. 5

6 PROSELECT DISCOVERY PROCESS 6

7 ProSelect Discovery Process SCIENCE Lit review and target identification Assay development Bacteria screening Safety assessment Pre-clinical: safety and proof of concept Pre-clinical: efficacy and mechanism Clinical efficacy/safety studies Additional clinical work PRODUCTION Lab scale optimization Pilot scale up with third party manufacturer Industrial scale up Product formulation REGULATORY Safety dossier GRAS dossier preparation including self affirmation, pre-notification meeting with the FDA and filing 7

8 Cardioviva Discovery Process ~350 strains for BSH activity 53 Lactobacillus strains screened in vitro 29 Lactobacillus strains positive BSH activity 28 Lactobacillus strains validated BSH activity 9 Lactobacillus strains validated GIT viability 9 Lactobacillus strains for MIC 4 Lactobacillus strains suited commercialization 3 Lactobacillus strains screened in hypercholesterolemic F1B Hamster model 2 Lactobacillus strains screened in human clinical studies 1 Lactobacillus reuteri (NCIMB 30242) lowers LDL-C in human clinical trial 8

9 CARDIOVIVA BASICS 9

10 Cardioviva Basics The world s only probiotic carefully selected through proprietary technology that has been shown to naturally help reduce LDL-cholesterol, a risk factor for heart disease, by 11.6 percent in hypercholesterolemic adults. The only probiotic that has been shown to help reduce total cholesterol and LDLcholesterol levels in hypercholesterolemic adults, through the microbiome in the gut. A natural probiotic supplement and ingredient for a wide range of foods and beverages that is safe to consume daily. Carefully formulated for convenient use as a small, easy to swallow capsule with no unpleasant aftertaste. 10

11 Cardioviva Basics Probiotic strain: Cardioviva (Lactobacillus reuteri NCIMB 30242) Colony-forming units (CFU): 2 x 109 (2 billion) (80 mg) live bacteria up to the date of expiration One capsule (100 mg) with food twice daily Cardioviva will be available in supplement form to the Canadian market late 2012, and the U.S. market early

12 Professional Resources Available at mycardioviva.com 12

13 CARDIOVIVA MECHANISM, CLINICAL TRIALS, SAFETY 13

14 Mechanism of Action Cardioviva helps reduce LDL and total cholesterol levels, risk factors for heart disease, in two ways: By reducing the amount of cholesterol your body produces By reducing the amount absorbed from food Cardioviva produces an enzyme called bile salt hydrolase that deconjugates bile acids. These bile acids are neutral detergents made by the liver from cholesterol and are released into the intestine with the purpose of transporting dietary fat and cholesterol into the circulation. As bile acids are deconjugated by Cardioviva in the intestines, dietary and biliary cholesterol absorption is reduced and the recirculation of bile is altered resulting in better control of LDL-C levels in blood. 14

15 Mechanism of Action Bile Salt Hydrolysis (BSH) Cholesterol Catabolism (FXR) Sterol Absorption (NPC1L1) Sterol Excretion (ABCG5/8) Cholesterol 15

16 Trial I: Design Objective: To evaluate the cholesterol lowering efficacy and safety of a L. reuteri NCIMB yogurt formulation in mildly hypercholesterolemic adults Design: Randomized, double blind, placebo controlled, parallel arm, multicenter trial Investigational Product: 1 x 10^10 CFU BID in microencapsulated yogurt format Duration: 6 week intervention ITT: N 114 subjects (n 58 placebo, n 56 treatment) Primary endpoint: LDL-C at 6 week endpoint relative to placebo Secondary endpoints: LDL-C, TC, apob- 100, non-hdl-c, HDL-C, TG, biochemistry, hematology, fecal microflora, fecal deconjugated bile Additional endpoints: Demographic data, diet journal data, GI questionnaire data 16

17 Trial I: Cholesterol Lowering Efficacy LDL-C: -8.92% (P=0.02)* TC: -4.81% (P=0.03)* apob-100: -6.81% (P=0.046)* non-hdl-c: -6.01% (P=0.025)* No change in TG and HDL-C* Balanced diet income between treatment groups** No change in fecal bile acids* No adverse events No change in safety parameters that considered as substantial or connected to treatment *ANCOVA/Kruskal-Wallis **ANOVA/Kruskal-Wallis ClinicalTrials.gov Identifier: NCT

18 Trial II: Design Objective: To evaluate the cholesterol lowering efficacy and safety of a L. reuteri NCIMB capsule formulation in mildly hypercholesterolemic adults over 9 weeks Design: Randomized, double blind, placebo controlled, parallel arm, multicenter trial Investigational Product: 2.5 x 10^9 CFU (100mg) BID in capsule format Duration: 9 week intervention ITT: N 127 subjects Primary endpoint: LDL-C at 9 week endpoint relative to placebo Secondary endpoints: LDL-C, TC, apob100, apoa1, non-hdl-c, HDL-C, TG, hs-crp, fibrinogen, free and esterified cholesterol, bile acid profile, plant sterols, biochemistry, hematology Additional endpoints: Demographic data, diet journal data, GI questionnaire data ClinicalTrials.gov Identifier: NCT

19 Trial II: Cholesterol Lowering Efficacy At the 6 week point and 9 week endpoint compared to placebo, Cardioviva capsules resulted in: significant reductions in LDL-C of 11.64% TC of 9.14% non-hdl-c of 11.30% ApoB-100 of 8.41% 19

20 Trial II: Individual LDL-C Response Matched individual LDL-C responses indicate a therapeutic effect of Cardioviva capsules independent of response and with a high rate of response. 20

21 Trial II: Improved CVD Risk Profile Cardioviva capsules resulted in significantly improved lipid ratios at the 6 week point and 9 week endpoint and significantly reduced CVD risk factors at the 9 week endpoint. 21

22 Trial II: Improved CVD Risk Profile hs-crp Fibrinogen % of patients % of patients 2% Figure: % of patients who decrease their hs-crp risk profile by 1 or 2 risk groups after taking placebo or Cardioviva for 9 weeks. Criteria for hs-crp levels and associated cardiovascular risk: low risk < 1mg/l; average risk 1-3 mg/l; high risk > 3mg/l. Figure: % of patients who decrease their fibrinogen risk profile by 1 or 2 risk groups after taking placebo or Cardioviva for 9 weeks. Criteria for fibrinogen levels and associated cardiovascular risk: low risk < 2.36 g/l; average risk g/l; high risk > 2.77 g/l. 22

23 Trial II: Bile Deconjugation Correlated to LDL-C Reduction Figure: Individual changes in plasma deconjugated bile acids (DBA) and serum LDL-cholesterol (LDL-C) over the intervention period. A significant association was observed in subjects taking Cardioviva (Spearman correlation, r=-0.369, P=0.003) while no association was observed in subjects taking Placebo (Spearman correlation, r=0.086, P=0.516). It was also noted that the regression coefficients of the Placebo and Cardioviva groups were significantly different (P=0.012). 23

24 Trial III: Design Objective: To evaluate the cholesterol lowering efficacy and safety of a L. reuteri NCIMB capsule formulation in mildly hypercholesterolemic adults over 12 weeks Design: Randomized, double blind, placebo controlled, parallel arm, multicenter trial (3 US + 1 CAN) Duration: 12 weeks intervention ITT: N = 150 subjects Primary endpoint: LDL-C at 12 weeks Secondary endpoints: LDL-C, TC, apob- 100, apoa-1, non-hdl-c, HDL-C, TG at 6 and 12 weeks Safety endpoints: adverse events, vitals, physical exam, clinical exam, biochemistry, hematology Inflammatory endpoints: hs-crp, fibrinogen, homocysteine Additional endpoints: Diet journals ClinicalTrials.gov Identifier: NCT

25 Key Clinical Outcomes Two randomized double-blinded, placebo-controlled, multicenter trials have shown that Cardioviva healthy bacteria lowered total and LDL-cholesterol in hypercholesterolemic adults. A third clinical trial is underway with sites in both Canada and the United States. The ability of Cardioviva to help reduce blood C-reactive protein (CRP) levels, a clinical marker for inflammation and risk factor in heart disease, is demonstrated in one clinical study; a second is underway. 25

26 Efficacy, Safety and Toxicology Strain Safety Clinical Safety Clinical Safety Branton et al. Int J of Probiotics and Prebiotics Vol. 6, No. 1, pp. 1-12, Jones et al. Food Chem Toxicol Mar 15;50(6): Jones et al. Regul Toxicol Pharmacol Jul 63;(2): Clinical Efficacy Clinical Efficacy Jones et al. Br J Nutr May 107;(10): Jones et al. Eur J of Clin Nut. advance online publication, Sept 19, 2012 ; doi: /ejcn

27 Safety Cardioviva is a natural probiotic supplement and ingredient for a wide range of foods that is safe to consume daily. Health Canada has issued a Product License Application Exemption Number for Cardioviva based on its LDL-and total cholesterol lowering properties. Cardioviva is self-affirmed Generally Regarded As Safe (GRAS) in the United States and full GRAS Notification has been submitted to the FDA. In Europe, the Cardioviva probiotic strain Lactobacillus reuteri has Qualified Presumption of Safety (QPS) status. In Australia, the Cardioviva probiotic strain Lactobacillus reuteri is on the Therapeutic Goods Administration s (TGA) approved list of medical ingredients. 27

28 WHY RECOMMEND CARDIOVIVA 28

29 Why Recommend Cardioviva Cardioviva can be a safe and natural addition to a heart healthy diet and lifestyle. Many adults need help in maintaining healthy cholesterol levels because they exceed levels recommended by doctors to help prevent heart disease. Healthy people who like the digestive benefits of probiotics but are also interested in maintaining healthy and normal levels of cholesterol may benefit from Cardioviva. Cardioviva will be available in supplement form to the Canadian market late 2012, and the U.S. market early

30 Dietary Cholesterol Management Options Table: Effective dose and cholesterol reduction of nutritional ingredients Cardioviva (L. reuteri NCBIM 30242) Effective dose (g/day) * TC reduction vs. placebo (%) LDL-C reduction vs. placebo (%) Effect on HDL/LDL ratio Effect on CV inflammatory markers Effect on GI health Yes Yes Yes Phytosterols Yes No No Fish oil/omega- 3/DHA/EPA Yes Yes No Oat β-glucan Yes No Yes Psyllium fiber Yes No Yes Soy protein Yes No No Reference Jones et al., 2012a; Jones et al., 2012b; Ooi et al Abumweis et al., 2008; Ortega et al., 2006; Talati et al., 2010; FDA, 2010; EFSA 2012 Hooper et al. 2004; Skulas-Ray et al., 2011; EFSA, 2012; Othman et al. 2011; Tiwari and Cummins, 2011; EFSA, 2010; EFSA, 2011; NCEP-ATP III, 2002 Wei et al., 2009; Anderson et al., 2000; NCEP-ATP III, 2002 McVeigh et al., 2006; Anderson and Bush, 2011; FDA, 1999; Erdman, 2000; NCEP-ATP III, 2002 * Effective dose in grams of dry ingredient 30

31 Efficacious Dose of Non-Statin Cholesterol Lowering Adjuncts Dose (grams/day) Reported efficacious dose Reference: Zetia (Ezetimibe) product monograph 2012, Jackevicius et al ; Jones et al. 2012; Niaspan (Extended-release Niacin) product monograph 2011, Bassan 2012; Lipidil Micro (Fenofibrate ) product monograph 2011, Lopid (Gemfibrozil) product monograph 2010; Abumweis et al. 2008, Ortega et al. 2006, Talati et al. 2010, FDA 2010, EFSA 2012; EFSA 2010; Othman et al. 2011, Tiwari and Cummins 2011, EFSA 2010, EFSA 2011, NCEP-ATP III 2002; Wei et al. 2009, Anderson et al. 2000, NCEP-ATP III 2002; Welchol (Colesevelam hydrochloride) product monograph 2011, Colestid (Colestipol hydrochloride) product monograph 2011; McVeigh et al. 2006, Anderson and Bush 2011, FDA 1999, Erdman 2000, NCEP-ATP III

32 ABOUT MICROPHARMA LIMITED 32

33 Who We Are Micropharma Limited, a pioneer in the development of innovative and effective probiotics, is launching a portfolio of natural supplements and food ingredient solutions aimed at addressing specific health markers to help maintain and improve health and wellness. Micropharma is specifically focused on products that address the healthy and natural metabolic balance and functioning of the microbiome, its resulting impact in the body and improving human health. Micropharma s product development approach is supported by extensive research to ensure that the most effective products are developed. Micropharma will out-license these products to partners for commercialization in the medical food, consumer healthcare, and food ingredient markets. 33

34 Cardioviva Milestones 34

35 FOR MORE INFORMATION mycardioviva.com micropharma.net (514)