Developing medicines based on cannabinoid science

Transcription

1 Developing medicines based on cannabinoid science

2 Important Notice Emerald Health Pharmaceuticals Inc. (the Company) is currently Testing the Waters under Regulation A+ (Regulation A+) under the Securities Act of 1933, as amended. The offering will be made only by means of an offering circular. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. No money or other consideration is being solicited at this time, and if sent in response to these materials, it will not be accepted. No securities may be sold, and no offer to buy securities can be accepted and no part of the purchase price can be received for an offering under Regulation A+ until an offering statement is qualified by the U. S. Securities and Exchange Commission, and any such offer may be withdrawn or revoked, without obligation or commitment of any kind, at any time before notice of its acceptance given after the qualification date. A person's indication of interest in a Regulation A+ offering is non-binding and involves no obligation or commitment of any kind. The Offering Circular is available via this URL: Cautionary Note Regarding Forward- Looking Statements TO THE EXTENT STATEMENTS CONTAINED IN THE FOLLOWING PRESENTATION ARE NOT DESCRIPTIONS OF HISTORICAL FACTS REGARDING THE COMPANY, THEY SHOULD BE CONSIDERED FORWARD-LOOKING STATEMENTS, AS DESCRIBED IN THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995, THAT REFLECT MANAGEMENT S CURRENT BELIEFS AND EXPECTATIONS. YOU CAN IDENTIFY FORWARD-LOOKING STATEMENTS BY WORDS SUCH AS ANTICIPATE, BELIEVE, COULD, ESTIMATE, EXPECT, FORECAST, GOAL, HOPE, HYPOTHESIS, INTEND, MAY, PLAN, POTENTIAL, PREDICT, PROJECT, SHOULD, STRATEGY, WILL, WOULD, OR THE NEGATIVE OF THOSE TERMS, AND SIMILAR EXPRESSIONS THAT CONVEY UNCERTAINTY OF FUTURE EVENTS OR OUTCOMES. FORWARD-LOOKING STATEMENTS CONTAINED IN THESE PRESENTATIONS INCLUDE, BUT ARE NOT LIMITED TO, STATEMENTS REGARDING: (I) THE SUCCESS AND TIMING OF OUR PRODUCT DEVELOPMENT ACTIVITIES AND CLINICAL TRIALS; (II) OUR ABILITY TO DEVELOP OUR PRODUCT CANDIDATES; (III) OUR PLANS TO RESEARCH, DISCOVER, EVALUATE AND DEVELOP ADDITIONAL POTENTIAL PRODUCT, TECHNOLOGY AND BUSINESS CANDIDATES AND OPPORTUNITIES; (IV) OUR ABILITY TO DEVELOP AND MANUFACTURE OUR PRODUCT CANDIDATES AND TO IMPROVE THE MANUFACTURING PROCESS; (V) OUR ABILITY TO ATTRACT AND RETAIN KEY SCIENTIFIC OR MANAGEMENT PERSONNEL; (VI) THE ANTICIPATED TIMING OF CLINICAL DATA AVAILABILITY; (VII) OUR ABILITY TO MEET OUR MILESTONES; (VIII) OUR EXPECTATIONS REGARDING OUR ABILITY TO OBTAIN AND MAINTAIN INTELLECTUAL PROPERTY PROTECTION; AND (IX) THE IMPACT OF CAPITAL MARKET CONDITIONS ON US. FORWARD-LOOKING STATEMENTS ARE SUBJECT TO KNOWN AND UNKNOWN FACTORS, RISKS AND UNCERTAINTIES THAT MAY CAUSE ACTUAL RESULTS TO DIFFER MATERIALLY FROM THOSE EXPRESSED OR IMPLIED BY SUCH FORWARD LOOKING STATEMENTS. UNDUE RELIANCE SHOULD NOT BE PLACED ON FORWARD-LOOKING STATEMENTS. WE UNDERTAKE NO OBLIGATION TO PUBLICLY UPDATE ANY FORWARD-LOOKING STATEMENTS. THE COMPANY S INVESTIGATIONAL DRUG PRODUCTS HAVE NOT BEEN APPROVED OR CLEARED BY THE FDA. E m e r a l d P h a r m a. L I F E

3 Emerald Health Pharmaceuticals Status: Private Headquarters: San Diego, CA, USA R&D: Córdoba, Spain & Collingwood, VIC Australia Focused on developing patented synthetic cannabinoid-derived drug candidates to treat diseases with unmet medical need

4 Emerald Health Pharmaceuticals: Key Highlights Combining nature & science to cure deadly diseases Clinical Stage Development Broad Pipeline & Significant Market Competitive Advantage Strong Team Currently Seeking Private Financing Phase I initiated Broad patent First CBD Led by Price: on lead product protection derivative in experienced US$5.00/share candidate Phase 2 being planned for multiple sclerosis & scleroderma US$39B market opportunity in diseases with significant unmet needs clinical development Unique mechanism of action biotech/pharma executives and globallyrecognized cannabinoid scientists Valuation: US$50M IPO planned in 2019/20 The foundation is the endocannabinoid system (ECS)

5 The Endocannabinoid System Exists Throughout the Body Distribution of CB1 Receptors Receptors CB1 Psychotropic, health benefits CB2 GPR55 TRPV1 FAAH Non-psychotropic, health benefits PPARs MALG TRPA1

6 The ECS Creates Homeostasis in the Body Cannabis & cannabinoids THC affect the ECS More receptors than any other system in the body THC is the only psychotropic molecule (interacts with CB1) ECS deficiency may be a contributor to many diseases Many health benefits associated with nourishment of the ECS

7 How The ECS Can Be Affected 1. Endocannabinoids: cannabinoids produced by our bodies (e.g., anandamide) 2. Phytocannabinoids: molecules and compounds produced in plants, such as the cannabis sativa plant (e.g., medical cannabis, THC, CBD) 3. Synthetic cannabinoids: derived from natural or synthetic cannabis molecules 4. Natural non-cannabis substances: can modulate the ECS 8 cannabinoids are the main focus for medical use (only THC is psychotropic)

8 Health Effects of Cannabinoids EHP s focus: Derivatives of CBD and CBG CBD & CBG have multiple positive physiologic effects Research indicates they are: - Anti-inflammatory - Antioxidative - Neuroprotective - Analgesic - Anti-infective - Non-psychoactive

9 Global Trend to Legalize Cannabis for Medicinal Purposes The World Health Organization on CBD: There are no case reports of abuse or dependence relating to the use of pure CBD. No public health problems have been associated with the use of pure CBD. CBD is generally well tolerated with a good safety profile.

10 The Use of Cannabinoids: Combining Nature and Science Step 1 THC: the only psychoactive molecule ~150 cannabinoids in the marijuana plant Step 2 CBD (cannabidiol) Step 3 Non-psychotropic, Totally Synthetic NCEs Non-psychotropic Many health benefits Improved receptor targeting Potential to treat diseases Patented New, patented cannabinoid molecules

11 EHP s Scientific Approach Goal:Improve on the positive health effects of cannabis molecules by modifying them to create novel products with enhanced capabilities AUGMENT CBD & CBG receptor targeting FOCUS on receptors that can treat diseases with unmet medical need DEVELOP composition of matter patented cannabinoid new chemical entities (NCEs) CREATE a strong IP portfolio

12 Rational Drug Design PPAR CB 2 EHP s Cannnabinoid CB2 TRPV1 Library VCE CBD HU-331 VCE a CBD derivative GPR55 FAAH PPARg DRUG DISCOVERY SCREENING PLATFORM FOR ECS PPARs TRPA1 MALG TARGETS VCE A CBG derivative

13 Patents in our Molecule Library 14 patented CBD derivatives 11 issued, 20 pending, covering 25 molecules EHP s proprietary molecules, which are modified cannabinoids, are new chemical entities that do not exist in nature They qualify for the strongest type of patent covering composition of matter (which natural 11 patented CBG derivatives cannabinoids from cannabis cannot receive) Protection to 2037 Potential for multiple products & indications

14 Provides Many Therapeutic Opportunities Neurodegenerative Parkinson s disease Inflammatory Ulcerative Colitis / Crohn s Auto-Immune Huntington s disease Fibrotic Metabolic Cancer E m e r a l d P h a r m a. L I F E Scleroderma

15 Development Roadmap NOTE: In the scientific literature: EHP-101 = VCE EHP-102 = VCE emeraldpharma.life

16 Lead Product Candidate: EHP-101 CBD Cannabidiol (CBD) derivative CBD: Does not bind to CB1 (non-psychotropic) Safe, anti-inflammatory, neuroprotective, EHP-101 analgesic, anti-proliferative Helps improve MS symptoms

17 EHP-101: Why Multiple Sclerosis? Chronic inflammatory, degenerative, demyelinating CNS disorder Main symptoms of Multiple Sclerosis Our molecule targets receptors associated with MS Current medications are most effective only during the inflammatory phase; less potent as the disease transitions to a neurodegenerative process No effective disease-modifying drugs for progressive forms No therapies appear to re-myelinate damaged neurons

18 EHP-101 Can Potentially Re-Myelinate Nerves Damaged by MS Normal Multiple Sclerosis

19 EHP-101: Designed for Mechanism of Action Our strategy: CBD Reduces neuroinflammation To improve on CBD s known PPARγ positive effects by affecting validated targets in MS: Neuroprotection - PPARγ - CB2 - HIF EHP 101 CB2 Neuron survival and repair (alt. M2 activation, arginase-1) PPARγ: Peroxisome proliferator-activated receptor gamma CB2: Cannabinoid receptor Type 2 HIF: Hypoxia inducible factor HIF 1 HIF 2 Remyelination

20 EHP-101: Efficacy Demonstrated in MS Two widely accepted animal models of MS (EAE & TMEV) Significant reduction in clinical signs and disease progression Dose response with efficacy at 5 mg/kg Control (untreated): ) ) Treated:

21 EHP-101: Second Indication - Scleroderma Chronic, systemic autoimmune disease causing fibrosis of skin and internal organs Rare, life-threatening disease No SSc-specific approved drugs Current therapies not effective and have significant toxicities Lung fibrosis is a common cause of death (~60% mortality in 10 years)

22 EHP-101: Why Scleroderma? EHP-101 targets MoA in scleroderma Inhibition of collagen synthesis PPARγ and CB2: extensively studied molecular targets for the treatment of scleroderma* CB2 agonist Inhibition of ERK activation Fibroblast migration decrease Combined effect on PPARγ, CB2 EHP 101 PPARγ agonist myofibroblast differentiation and HIF not described for other types of marketed drugs Anti-inflammatory activity in vivo Pre-clinical proof-of-concept established in relevant animal models HIF Antifibrotic activity in vivo *Minghua et al, Tavarares et al, Akhmetshina et al, Del Rio et al Vascular protection

23 EHP-101: Path to the Clinic H1 Formulation (oral), initiated GLP tox studies and manufacturing for Phase I 2017 H2 US FDA grant of Orphan Drug Designation (ODD) for systemic scleroderma (SSc) and Huntington s disease EU EMA grant of ODD for SSc H1 Final clinical-enabling studies completed 2018 Pre-IND meeting with US FDA (for MS Phase II preparation) H2 Phase I human study initiated in Australia (single Phase I study expected to support Phase II in both MS & scleroderma) H1 Pre-IND meeting planned with US FDA (for SSc Phase II preparation) 2019 H2 Complete Phase I study Phase IIa human study planned to start in Q4 (Phase IIb study expected to start in the US, Canada, Australia in 2020)

24 EHP-102: Second Product Candidate Cannabigerol (CBG) derivative CBG CBG: Does not bind to CB1 (non-psychotropic) Provides neuroprotection in models of Huntington s disease, partially through antioxidant and anti-inflammatory activity, and PPARγ modulation EHP-102 Suppresses norepinephrine, providing muscle relaxation and analgesic properties through effects on the CNS

25 EHP-102: Why Parkinson s Disease? Chronic, progressive neurodegenerative disorder with no current cure More than 10 million people worldwide have Parkinson's disease A disease where damaged neurons do not produce sufficient dopamine (dopamine helps transmit impulses from the brain to the muscles) EHP-102 provides neuroprotection, partially through PPARγ activity and reduction in proinflammatory mediators

26 Oral VCE (20 mg/kg) in sesame oil Pole test Immunostaining density (%versus non lesioned side) EHP-102: Efficacy Demonstrated in PD Demonstrated efficacy in PD models Cylinder rearing test Improves clinical symptoms and recovers 30 movement parameters Latency (s) * ## SHAM 6-OHDA + vehicle 6-OHDA + VCE Score (preference for ipsilateral paw) ** # SHAM 6-OHDA + vehicle 6-OHDA + VCE (motor coordination and activity) Oral VCE (20 mg/kg) in sesame oil in the 6-OHDA model Lesioned side Non-lesioned side Reduces inflammatory marker expression and prevents dopaminergic neuronal loss in the 6-OHDA model Efficacy also shown in the LPS model TH immunostaining *** ## *** SHAM 6-OHDA + vehicle 6-OHDA + VCE control + 6-OHDA of PD (J. Neuroinflammation. 2018, 15(1):19) + VCE-003.2

27 EHP-102: Why Huntington s Disease? Causes progressive breakdown of nerve cells An orphan disease EHP-102 targets PPARγ with improved activity Also targets other pathways involved in neuronal survival (ERK 1+2)

28 VCE Veh NeuN + BrdU + /BrdU + cells EHP-102: Efficacy Demonstrated in Huntington s Disease Clinical symptoms ameliorated Clinical Neuroprotection in models of HD: Viral Mut-Huntington model Improved motor function & clinical scores with EHP-102 Latency FoldIncrease Veh ** # VCE Veh VCE wthtt mthtt mthtt NeuN + cell/mm ## ** Veh VCE Veh VCE wthtt mthtt wthtt Neurogenesis DARRP32 + Cells/mm ** ## ** Veh VCE Veh VCE wthtt mthtt EHP-102 positively affects neuroprotection and neurogenesis EHP-102 also showed efficacy in QA and 3NP models of HD Striatal DCX + cells/mm 2 a ## ### ** Veh EHP-102 Veh EHP-102 mthtt b ## ### ** 80 *** Veh EHP-102 Veh EHP-102 (Scientific Reports Jul 19;6:29789) wthtt mthtt wthtt mthtt

29 Publications by Our Team NATURE NATURE OPEN * * * γ γ γ γ in vivo + Cannabinoids the main active compounds of marijuana (Cannabis sativa), and its endogenous counterparts anandamide and 2-arachidonoyl glycerol have attracted the interest of the scientif c community in the last decade owing to their prominent ef ects on neurodegenerative and neuroinf ammatory conditions1. Cannabinoids exert neuroprotective actions in various experimental models of neurodegenerative diseases, and most of their ef ects are mediated via the presynaptic CB1 receptor. CB1 receptor levels notably diminish at early stages of Huntington s EmeraldPharma.LIFE *

30 Experienced Pharma & Biotech Management Avtar Dhillon, MD Chairman Chairman of 5 public life science companies, led turnaround of NASDAQ:INO from $10m to $550m Jim DeMesa, MD, MBA Chief Executive Officer 29 years in pharma product development and management, including preclinical and clinical trial management, and partnering with pharma companies. 15 years as CEO of public biotech companies. Lisa Sanford, CPA Chief Financial Officer 30 years of diversified finance and accounting experience in life sciences, pharmaceuticals and biotechnology. Eduardo Muñoz, MD, PhD Chief Scientific Officer, SAB Chairman 30 years in biomedical research, Professor of Immunology, author of 200 articles, patents and book chapters with nearly 5,000 citations Alain Rolland, PharmD, PhD Chief Development Officer 30 years of leadership experience in R&D, strategic and business development Nancy Coulson VP, Regulatory Affairs 30 years in global pharma and biotech regulatory mgmt with J&J, BMS, and others. Joachim Schupp, MD, Dr. med VP, Medical Affairs 30 years in clinical drug development, medical monitoring and clinical trial mgmt with Ciba-Geigy, Novartis, & others Giovanni Appendino, PhD Scientific Advisor, SAB One of the worlds thought leaders in cannabinoid research; Professor of Pharmaceutical Chemistry at the University of Eastern Piedmont; Author of 250 articles and 10 book chapters. Rao Movva, PhD Scientific Advisor, SAB 30 years in drug discovery and development; Novartis Distinguished Scientist; pioneered chemical biology efforts that led to the discovery and the understanding of TOR pathways Clinical Advisory Boards: MS: Emmanuelle Waubant, MD, PhD Juan Antonio Garcia-Merino, MD, PhD SSc: John Varga, MD Janet Pope, MD Patricia Carreira, MD

31 Thank You T O LEARN MORE PLEASE CONT ACT : Jim DeMesa, MD CHIEF EXECUT IVE OFFICER EM ERALD HEALTH PHARM ACEUTICALS Bernie Hertel VP FINANCE & COMMUNICAT ION S EM ERALD HEALT H SCIENCES T E. JIMDEMESA@EMERALDPHARM A.LIFE T E. BH@EMERALD.LIFE