EXPERIENTIAL STRESS RELIEF & ENHANCED COGNITIVE FUNCTION

Transcription

1 EXPERIENTIAL STRESS RELIEF & ENHANCED COGNITIVE FUNCTION

2 TABLE OF CONTENTS Presentation Overview OVERVIEW Highlights Safety SCIENTIFIC EVALUATION Clinical Efficacy Effects on Cognitive Function,, Stress Reduction & Mood Enhancement Mechanism of Action SOCIAL RESPONSIBILITY Vertical Integration Socially Responsible REGULATORY & TECHNICAL Regulatory Status Product Application 2

3 ZEMBRIN OVERVIEW & BACKGROUND 3

4 HIGHLIGHTS Landmark Achievements Clinically evaluated for safety & efficacy Supported by >300 years of indigenous use Patented Standardized & vertically integrated from seed to extract Self-affirmed GRAS Ecologically & socially responsible No withdrawal effects 4

5 OVERVIEW Zembrin - an Exclusive Selection of Sceletium Unique selection of the South African plant Sceletium that is rich in mesembrenone, and low in mesembrine developed into a proprietary, standardized extract, trade marketed as All studies, safety data, claims, patents, bioprospecting permits and export permits are related to the proprietary standardized extract and is not applicable to other forms of Sceletium 5

6 SCELETIUM EFFICACY Origins of Sceletium Use For Mood, Stress, Cognitive Health Indigenous Use Use documented as early as 16 th century Currently used for physical and emotional stress and to induce wellbeing In vivo Animal Studies Decreased excessive barking in dogs Decreased cage and travel stress in cats Improved dementia in dogs and cats Published Clinical Case Studies* Reports of improved mood, anxiety, energy & focus Patients with major depression, anxiety or personality disorder *Gericke, N. Clinical application of selected South African medicinal plants. Australian Journal of Medical Herbalism 2001 (13)

7 SAFETY Confirmed by a Full Array of Safety & Toxicity Evaluations PUBLISHED CLINICAL SAFETY STUDY 1 : A RCT evaluation of 25mg of Zembrin in 36 healthy adult volunteers over a 12 week period Zembrin was safe and well tolerated PUBLISHED IN VIVO SAFETY STUDIES 2 : No chronic toxicity (90 day study) at 600 mg/kg per day No acute toxicity (14 day study) at 5000 mg/kg IN VITRO: No toxicity; Ames test, Micronucleus, herg 1 Nell et al (2013) A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Extract Sceletium tortuosum (Zembrin) in Healthy Adults. J Alt Compl Medicine 18:1-7 2 Murbach et al (2014) A toxicological safety assessment of a standardized extract of Sceletium tortuosum (Zembrin) in rats Food and Chemical Toxicology 74:

8 SCIENTIFIC EVALUATION WEIGHT MANAGEMENT CLINICAL SAFETY & EFFICACY STUDIES 8

9 CLINICAL EFFICACY 3 Clinical Trials Conducted with Zembrin 1 Terburg D et al Acute Effects of Sceletium tortuosum (Zembrin), a Dual 5-HT Reuptake and PDE4 Inhibitor, in the Human Amygdala and its Connection to the Hypothalamus. Neuropsychopharmacology Chiu et al Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer s Dementia Evidence-Based Complementary and Alternative Medicine 3 Nell et al A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Extract Sceletium tortuosum (Zembrin) in Healthy Adults. J Altern Compl Med 18:1-7. Functional MRI, Anxiolytic (Terburg et al, 2013) 1 Cognitive Function (Chiu et al, 2014) 2 Safety & Tolerability (Nell et al, 2013) 3 9

10 PUBLISHED PHASE 1 SAFETY STUDY Clinical evaluation for 12 weeks demonstrates safety in humans STUDY DESIGN Objective: To evaluate safety and tolerability of Zembrin at two levels of intake (8 mg/d or 25 mg/d) Randomized, double-blind, placebo controlled clinical trial 37 healthy volunteers, age years old PHASE 1 SAFETY STUDY ZEMBRIN SHOWN TO BE WELL-TOLERATED No differences among the 3 treatment groups in vital signs, ECG, body weight and physical exam between baseline and end of study. Unsolicited positive effects on wellbeing were noted by some participants taking Zembrin, including improved coping with stress and sleep. Nell et al A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Extract Sceletium tortuosum (Zembrin) in Healthy Adults. J Altern Compl Med 18:

11 EFFECTS ON COGNITIVE FUNCTION Clinical Trial Details Chiu et al STUDY SITE University of Western Ontario, Canada PI: Dr. Simon Chiu Clinical Investigator: Dr. Michael Woodbury DOUBLE-BLIND, PLACEBO- CONTROLLED CROSSOVER STUDY 21 volunteers (male and female), mean age years 25 mg of Zembrin or placebo daily Healthy Population: No DSM IV-R cognitive or mood disorders COGNITION MOOD PSYCHOMOTOR FUNCTION Chiu et al Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer s Dementia Evidence-Based Complementary and Alternative Medicine 11

12 COGNITIVE FUNCTION Clinical Study Design Chiu et al 3 Weeks Active/Placebo 3 Weeks Washout PARAMETERS EVALUATED Primary: Cognitive Function (CNS VitalSign battery of tests)* Secondary: Mood: Hamilton Depression Rating Scale (HAM-D) Safety & Tolerability *CNS VitalSign has been used for testing neurocognitive function by over 5000 clinicians in 52 countries 3 Weeks Placebo/Active Chiu, et al

13 COGNITIVE FUNCTION Zembrin Significantly Improved Key Cognitive Domains COGNITIVE FLEXIBILITY Ability to shift attention between two or more tasks and the ability to adapt to rapidly changing directions and intelligently utilize the information. Necessary for decision-making, impulse control and strategy formation. CNS VitalSign has been used for testing neurocognitive function by over 5000 clinicians in 52 countries mean percentiles Cognitive Set Flexibility 35.4 Baseline *p < vs. placebo 60.2 * Zembrin 3 weeks 49.7 Placebo 13

14 COGNITIVE FUNCTION Zembrin Significantly Improved Key Cognitive Domains EXECUTIVE FUNCTION Refers to exercising initiative, proper judgment, discipline and the ability to operate in favor of an abstract reward. Spontaneous ability to take action and goal-directed behavior. Chiu et al CNS VitalSign has been used for testing neurocognitive function by over 5000 clinicians in 52 countries mean percentiles 36.8 *p < vs. placebo Executive Function Baseline 60.8 * Zembrin 3 weeks 50.1 Placebo 14

15 COGNITIVE IMPROVEMENTS Stress Reduction & Mood Enhancement HAM-D SCORE Gold-Standard to assess severity of depression and response to therapy in clinical research RESULTS Reduction of stress and improvement of mood manifested through: Statistically significant improved quality of sleep Less fatigue Enhanced work performance Enhanced interest in daily activities Less irritability, worry and insecurity Chiu et al Reduction of HAM-D Scores from baseline (%) 26.9% (p<0.075) Zembrin 13.8% (p<0.289) Placebo 15

16 STRESS MANAGEMENT Functional MRI (fmri) Evaluation Terburg et al, 2013 STUDY SITE University of Cape Town, South Africa Investigators: Drs. David Terburg, Dan Stein and Jack van Honk DOUBLE-BLIND, PLACEBO-CONTROLLED CROSSOVER STUDY 16 volunteers (male and female), years 25 mg of Zembrin or placebo single dose Healthy Population: healthy undergraduate students, no history of neurological or psychopathology 16

17 STRESS MANAGEMENT Crossover Clinical Study Design DESIGN 1 dose of Zembrin or Placebo MRI Scan 5 8 days Washout PARAMETERS EVALUATED Activation and Response of the brain to threat/stress via: Perpetual-load test Emotion-masking task 1 dose of Zembrin or Placebo MRI Scan Terburg D et al Acute Effects of Sceletium tortuosum (Zembrin), a Dual 5-HT Reuptake and PDE4 Inhibitor, in the Human Amygdala and its Connection to the Hypothalamus. Neuropsychopharmacology

18 STRESS MANAGEMENT fmri Study Results Show Reduced Stress Response ZEMBRIN MAY HELP IN THE MANAGEMENT OF STRESS IN EVERYDAY LIFE A single dose of Zembrin attenuates reactivity within the part of the brain (amygdala) that responds to threat/stress Terburg, et al (2013) 18

19 MECHANISM OF ACTION Working Hypotheses 1) PDE-4 INHIBITION Increases intracellular camp camp / cgmp regulation critical in memory-related processes Cognitive Function Neuroprotection Depression Alzheimer s Inflammation 2) INHIBITS 5-HT REUPTAKE Anxiolytic effect of SRI Stress negatively affects cognitive function DUAL EFFECT OF 2 ACTIVITIES (5-HT REUPTAKE AND PDE-4 INHIBITION) WORKING SYNERGISTICALLY 19

20 SOCIAL RESPONSIBILITY SUSTAINABLY & SOCIALLY DEVELOPED 20

21 1.5e6 1.0e6 0.5e6 VERTICAL INTEGRATION Zembrin Elite Plant Propagation and Production [AV1243_SC] TIC #

22 SOCIALLY RESPONSIBLE Ecologically Sustainable 1st ever export permit from South African government, full compliance under the Biodiversity Act International best practice benefit-sharing agreement with South African San Council Endorsement by indigenous people with the exclusive use of their trademark for a Sceletium product Biodiversity leadership hailed at UN Nagoya conference by Minister of the Environment Ecologically sustainable plant production & cultivation, to EU and Global GAP Reliable supply chain and validated QC through own propagation & production 22

23 REGULATORY & TECHNICAL PRODUCT APPLICATION EXAMPLE 23

24 REGULATORY AND IP STATUS Safety Data Supports Food & Supplement Use DIETARY SUPPLEMENTS Historical use NDI on-file at 25 mg / day FOOD Self-Affirmation GRAS IP STATUS US patent # 6,288,104 US patent # 8,552,051 US patent # 8,980,338 PCT/IB2010/ (pending) 24

25 PRODUCT APPLICATION - EXAMPLE The Energy Drink Reinvented Growing Consumer Concern about Mental Energy & Focus 39% % ex/v concerned 53% Source: 2010 HealthFocus International Increasing Dependence on Foods & Beverages for Help 14% 21% Always/Usually Choose Foods & Beverages to Improve Mental Performance 25

26 PRODUCT APPLICATION - EXAMPLE Mental Energy Drink Convergence of evidence supports use of Sceletium tortuosum for multiple benefits: Cognitive Function Focus Improved Mood Reduced Stress Mental Energy Drink for Calm Focus Caffeine- Free 26

27 OUR CORE VALUES MAKE US BETTER PARTNERS BENEFICIAL AND FAIR TO ALL HIGH COMMITMENT CULTURE INTEGRITY CREATIVITY ECSTATIC CUSTOMERS