Inmed Pharmaceuticals Inc. · NASDAQ:INM
Inmed Pharmaceuticals — Technical Presentation (November 2015)
26 slides from Inmed Pharmaceuticals's technical presentation, November 2015
Slide 1: Epidermolysis Bullosa: InMed Pharmaceuticals Development Program
Epidermolysis Bullosa InMed Pharmaceuticals Development Program November 2015 Designing Intelligent Medicines 1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements, including statements concerning anticipated clinical development activities, the potential benefits of product candidates and anticipated market opportunities. All statements other than statements of historical fact ar
Slide 3: Epidermolysis Bullosa – Disease Overview
Epidermolysis Bullosa – Disease Overview • Epidermolysis Bullosa (EB) is group of inherited connective tissue diseases that share a common manifestation of faulty protein anchors in the skin that result in extremely fragile skin that blisters or tears from friction or trauma • Each type and sub-type
Slide 4: Epidermolysis Bullosa - Pathophysiology
Epidermolysis Bullosa - Pathophysiology • The human skin consists of two major layers: – an outermost layer called the epidermis, and – a layer underneath called the dermis • In individuals with healthy skin, there are protein anchors between these two layers that prevent them from moving independen
Slide 5: Pathophysiology and Major Categories
Pathophysiology and Major Categories Major EB Type Layer of Blistering Major EB Subtypes Protein Dysfunction EB Simplex (EBS) Epidermis Basal EBS - K5, K14 - Plectin, ⍺6β4 integrin Suprabasal EBS - desmoplakin Junctional EB (JEB) Lamina lucida JEB Herlitz - Laminin-332 JEB, other - Laminin-332, Type
Slide 6: Pathophysiology and Structural Proteins
Pathophysiology and Structural Proteins Adapted from Medscape - Epidermolysis Bullosa Clinical Presentation, Author: M Peter Marinkovich, MD; Chief Editor: William D James, MD 6
Slide 7: EB – Clinical Manifestations
EB – Clinical Manifestations The hallmark feature of EB is mechanical fragility. This is invariably associated with the development of blisters • In most forms of EB, the blisters (or erosions) are filled with clear colorless exudate, or they may be hemorrhagic • The blistering and sores can be pain
Slide 8: Epidermolysis Bullosa – Current Therapies
Epidermolysis Bullosa – Current Therapies Currently treatment is similar to treatment given to burn victims: • non-adherent bandages, dressings and antiseptic washes for the blisters • various medications for pain, itching and inflammation • oral antibiotics for infections; preventative treatments s
Slide 9: INM-750: Development Rationale
INM-750: Development Rationale In designing a treatment for Epidermolysis Bullosa, InMed is seeking to: • Modify the course of the disease by restoring the anchoring function that has been lost due to dysfunctional proteins. – InMed is focusing specifically on restoring function in patients with epi
Slide 10: INM-750 and Disease Modulation in EBS
INM-750 and Disease Modulation in EBS 10
Slide 11: The Role of Keratin’s in Structural Integrity of the Skin
The Role of Keratin’s in Structural Integrity of the Skin • Keratins are a family of 30 proteins. They are the most abundant structural proteins in the cytoplasm of epithelial cells, in which they form a network of 10–12 nm wide intermediate filaments (IFs) • Keratin proteins are encoded by a large
Slide 12: Keratin Dysfunction in EBS
Keratin Dysfunction in EBS The Role of K5 and K14 in EBS • The vast majority of EBS cases (75%) are due to mutations affecting either K14 or K5 which are type I and II intermediate filament (IF) genes selectively expressed in basal keratinocytes in the epidermis and related complex epithelia • Becau
Slide 13: InMed’s Approach to Disease Modulation for EBS
InMed’s Approach to Disease Modulation for EBS • The most common cause of skin fragility in EBS is the dysfunction of either K5 or K14 • Evidence from the difference in keratin expression at different parts of the body suggest that there is some redundancy in the function of keratins, and that up re
Slide 14: InMed’s In vitro Testing Methodology for Keratin Expression
InMed’s In vitro Testing Methodology for Keratin Expresssion • Cell culturing – Testing in immortalized keratinocyte cell lines, cultured in medium, and supplemented with various solutions – Cultured at 37 C, medium changed every day • Expression of Keratins – qPCR was used to identify mRNA expressi
Slide 15: Regulation of Keratins (K5, K15 & K14) by Individual Cannabinoids
Regulation of Keratins (K5, K15 & K14) by Individual Cannabinoids - Example of study results INM-505, and INM-506 are internal InMed codes for specific cannabinoids 15
Slide 16: Summary of Results on Keratin Regulation
Summary of Results on Keratin Regulation Keratins INM-509 (µM) INM-505 (µM) INM-506 C (µM) INM-513 (µM) 0.1 1.0 10 0.1 1.0 10 0.1 1.0 10 0.1 1.0 10 P ⬇ - - - - ⬇ - - ⬇ - - K5 D - - - - - - - - ⬇ ⬇ ⬇ ⬇ P ⬇ - - - - ⬇ - - ⬇ - - ⬇ K14 D - - - - - ⬇ - - ⬇ - - ⬇ P ⬇ ⬆ ⬆ ⬆ - ⬆ ⬆ ⬆ - ⬆ ⬆ ⬆ K15 D - - ⬆ - ⬇ -
Slide 17: INM-750 and Symptom Management in EB
INM-750 and Symptom Management in EB 17
Slide 18: The Endocannabinoid System and the Skin
The Endocannabinoid System and the Skin Endocannabinoids and cannabinoid receptors have been implicated in multiple regulatory systems in the skin Barrier recovery Epidermis ↓ Barrier recovery Proliferation CB1/CB2 Melanogenesis Differentiation CB1 Inflammation CB1/CB2 Apoptosis ↓ Inflammation ↓ Deg
Slide 19: Potential Role of Cannabinoids in Symptom Regulation of EB
Potential Role of Cannabinoids in Symptom Regulation of EB EB Hallmark Pharmacological Action of Phyto-Cannabinoids Wound Healing and • The CB1 receptor is known to be involved in the keratinocyte migration, and thus it is Skin Regeneration postulated that cannabinoids can aid in wound healing Anti-
Slide 20: INM-750 and Wound Healing and Skin Regeneration
INM-750 and Wound Healing and Skin Regeneration 20
Slide 21: The ECIS - Wound Healing Assay
The ECIS - Wound Healing Assay Electric Cell-substrate Impedance Sensing (ECIS) Wounding Assay • The ECIS Wound Healing Assay replaces the traditional "scratch" or "scrape" assay. Instead of disrupting the cell layer mechanically with a toothpick, needle or pipette tip and following the migration of
Slide 22: INM-505 and INM-517 Accelerate Wound Closure by Human Keratinocytes
INM-505 and INM-517 Accelerate Wound Closure by Human Keratinocytes In Vitro (Chronic Wound Healing Process) Confluent monolayer T1 INM-505 and INM-517 are internal InMed codes for specific cannabinoids 20 hours • “Confluent monolayer” represents the closing of the skin layer on the test medium • “N
Slide 23: INM-750 and Wound Healing - Effect on MCP-1
INM-750 and Wound Healing - Effect on MCP-1 • MCP-1 attracts blood monocytes and macrophages to skin wound area and plays critical role in normal skin homeostasis and wound healing process • MCP-1 supports traffic and activation of Langerhance Cells and Macrophages strengthening innate (anti-infecti
Slide 24: INM-750 and Inflammation
INM-750 and Inflammation laMed Phermmaceuticals
Slide 25: INM-750 and Inflammation
INM-750 and Inflammation IL-8 • IL-8 is the most potent chemoattractant for blood Neutrophils and important mediator of angiogenesis. • Chronic IL-8 production and Neutrophil activation in the skin wound is unfavourable element of skin pathology. INM-505 (a specific cannabinoid studied by InMed) dis
Slide 26: INM-750: Product Selection
INM-750: Product Selection • INM-750 will include several cannabinoids as its active substance. Selection of the specific cannabinoids included in the final product is based on the following criteria (in order of priority): 1. Cannabinoids that will restore the structural integrity of the skin for E
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