Nugen Medical Devices Inc · TSXV:NGMD
Nugen Medical Devices — Technical Presentation (December 2020)
43 slides from Nugen Medical Devices's technical presentation, December 2020
Slide 1: Needle-free Intradermal Powder Injection Technology overview
Needle -free lntradermal Powder Injection Technology overview
Slide 2: Outline
Outline ■ Biolistic delivery principle ■ lnolife Powder Injector technology ■ Family of injector devices Formulation methods ■ Ability to target epidermis (pre-clinical and ex-vivo) Pain and local tolerance (clinical) ■ DNA vaccine delivery (pre-clinical) ■ Conventional vaccine delivery+ stability (
Slide 3: Technology Platform
Technology Platform Principle: Gas-propelled supersonic acceleration of microparticles into epidermis and/or dermis (i.e., biolistic or "gene gun" method of delivery). Pain-free/Fast/Easy Effective Thermostable Family of devices based on this platform
Slide 4: Intradermal particle delivery
lntradermal particle delivery lnolife Powder Injector= Accurate dose delivery at skin target depth controlled via particle size and density (formulation) and velocity (delivery).
Slide 5: Powder injection platform
Powder injection platform New needlefree injection principle for solids (powders) Membrane Dose of powder to inject Particles having ; penetrated the : skin at a controlled ‚ and uniform depth Guide tube Skin - To start the apparatus, the membrane is abruptly punctured (or withdrawn), which allows t
Slide 6: Family of devices
Family of devices ■ Single-dose pre-filled disposable ■ Multi-dose pre-filled disposable/refillable ■ Single-dose reusable sterilizable
Slide 7: Single-dose pre-filled disposable device
Single-dose pre-filled disposable device • < l $ per injector ■ Clinical or self-administered applications
Slide 8: Single-dose pre-filled disposable device
Single-dose pre-filled disposable device • < l $ per injector ■ Clinical or self-administered applications
Slide 9: Single-dose pre-filled disposable device
Single-dose pre-filled disposable device • < l $ per injector ■ Clinical or self-administered applications
Slide 10: Laboratory injector
Laboratory injector Gas microcylinder Single dose reusable and autoclave sterilisable. Built-in pressurized gas reservoir or pre-filled gas cartridge. Same device for animal and human trials.
Slide 11: Laboratory injector
Laboratory injector Single dose reusable and autoclave sterilisable. Built-in pressurized gas reservoir or pre-filled gas cartridge. Same device for animal and human trials.
Slide 12: Multi-dose pre-filled disposable device
Multi-dose pre-filled disposable device 50 doses at < 0,50$ per injection Individual dose capsules Mass vaccination & chronic self-administered applications.
Slide 13: IP portfolio
IP portfolio Patent Patent Technology awarded filed Working principle US patent 7,320,677 (2008) v Works with cheap gas cartridges U.S. App No. 61/570,911, PCT/CA2012/201142 (2011) v Improved platform U.S. Patent Application No. 61/824,651 (2013) v IP protection in Canada, U.S. and Europe
Slide 14: NuGen Powder Injector vs. Powderject & Powdermed
NuGen Powder Injector vs. Powderject & Powdermed ■ Powderject/Powdermed: ■ Uses converging-diverging nozzle ■ Complex device, high part count, expensive ■ Proprietary (discontinued) gas cylinder ■ Works poorly for conventional (protein) vaccines - formulation not suitable ■ NuGen Medical Devices Pow
Slide 15: Technological advantages
Technological advantages Safety/Convenience of device: No pain no bleeding no bruising Fast easy to use no sharps Improved Efficacy of delivery: Demonstrated dose reduction for conventional and DNA vaccines. Thermostable powder formulated vaccines eliminate cold supply chain. Can also easily formula
Slide 16: Better safety and convenience
Better safety and convenience - Eliminates pain and fear associated with needles. - Reduces infection risks - no skin response. no bleeding, no bruising. - Simple and quick delivery - can rapidly treat a large number of patients, can facilitate self-administration, can improve treatment compliance.
Slide 17: Improved efficacy
Improved efficacy Can target specific skin layers Reduces quantity of API Eliminates the need for costly adjuvants Achieves faster response Can inject pure drugs without response delaying excipient Can tailor formulation for controlled release. Can potentially achieve direct intracellular injection
Slide 18: Improved efficacy
Improved efficacy Epidermis is rich in antigen-presenting cells (APC) (Langerhans cells). Elicits both antibody and CTL responses. Dose reduction by a factor of 2.5-10 for conventional vaccines. Dose reduction by a factor of 100-1000 for DNA vaccines. as compared with IM needle injection
Slide 19: Improved stability
Improved stability Conventional vaccines and biologics are formulated with sugar-based solutions that are subsequently lyophilized, spray-dried or spray-freeze-dried. Demonstrated long-term stability at room temperature. Facilitate combination formulations since powders with different APls can be re
Slide 20: Formulation methods
Formulation methods ■ DNA vaccines (plasmids): Precipitation onto gold beads ■ Conventional vaccines (virus. sub-units. proteins): Proprietary thermostable formulation (based on spray-freeze-dry technique) - ability to produce dense mono-disperse particles that stabilize the antigen at elevated temp
Slide 21: DNA on inert beads formulation
DNA on inert beads formulation Precipitation of DNA plasmids on 3 mm gold beads Before formulation (SEM) After formulation SEM)
Slide 22: DNA on inert beads formulation
DNA on inert beads formulation DNA plasmid (HBsAg) deposition on either 3 mm gold beads or 15 mm glass beads. Recovered DNA after submerging beads in 50 ml TE as measured with NanoDrop spectrophotometer. Effective DNA plasmid formulation method on gold, tantalum and glass beads. Current results show
Slide 23: Proprietary thermostable protein formulation
Proprietary thermostable protein formulation ■ Spray-freeze-dry formulation= carbohydrate substrate + excipients + weighing agent+ active agent: ■ Long term stability at room temperature ■ Free-flowing (non clumping) ■ Proper size and density for biolistic delivery
Slide 24: Proprietary thermostable protein formulation
Proprietary thermostable protein formulation ■ Spray-freeze-dry formulation= carbohydrate substrate + excipients + weighing agent+ active agent SEM -SE SEM -RE
Slide 25: Thermostable formulation
Thermostable formulation SOS Page after 11 months HbSAg Hepatitis B protein antigen on weighed carbohydrate particles. MW I Quantity/band• Sµg - - 1: HBs Ag ., 50 ... 2: HBS Ag powder lot Feb 2011 ... 3: HBS Ag powder lot Jun 2011 4: HBS Ag powder lot Dec 2011
Slide 26: Thermostable formulation
Thermostable formulation SDS Page after 45 days - HA-New York Influenza inactivated virsu antigen with various adjuvants on carbohydrate particles. Influenza vaccine stability at room temperature after 45 days. 9:Mtigenonty 10:Antigen+Alum 11:Alumonty 12: Mtigen +Adjwant 13:Adjwantonly C:Sampleskept
Slide 27: Safety and convenience
Safety and convenience • Eliminates pain and fear associated with needles • Reduces infection risks • no skin response • no bleeding • no bruising • Simple and quick delivery -can rapidly treat a large number of patients, can facilitate self-administration, can improve treatment compliance. • Elimin
Slide 28: Pain-free delivery
Pain-free delivery (Human trial - I M saline vs pure salt powder injection) ■ Needle syringe (n=10) Powder injector (n:10) " Anticipated pain Pain felt Patient discomfort Marked difference between powder and IM needle injections. Powder= no bleeding, no bruising. 100% patient preference
Slide 29: Pain-free delivery
Pain-free delivery (Human trial - IM saline vs pure salt powder injection) Skin reaction Tabl•IS1'inn,achooafi<r nt<lcij,o -'" _ ,_mineo i • j_ « , _ >_m,•o • _j • - i « - - - - 1.ighObl«<ling Lighlbl«<ling GRl8 l.ightbl<,:,;Un!,s-.,mngonJmm GL19 1.igl,tbl«<l;ng.s-.,mng0rtJmm LiglUbl«<ling Nflll Lig
Slide 30: Ability to target epidermis
Ability to target epidermis Gold beads - Ex-vivo Human Skin surface Limit of Gold beads epidermis
Slide 31: Ability to target epidermis
Ability to target epidermis Gold beads - Ex-vivo Pig - ,,-
Slide 32: Ability to target epidermis
Ability to target epidermis Gold beads - In-vivo Mice
Slide 33: Control of injection depth
Control of injection depth Injection of 3 mm gold beads or 15 mm glass beads in live mice. Depth of penetration for various injection conditions .' a I __ . •_ _ : ! [i i·i ■ Changing injection parameters allows control over depth (target) of delivery.
Slide 34: Ability to target epidermis
Ability to target epidermis Thermostable particles - In-vivo Mice
Slide 35: Ability to target epidermis
Ability to target epidermis Thermostable particles - Ex-vivo Pig Skin surface
Slide 36: Delivered dose
Delivered dose • Measure from ex-vivo or in vivo pre-clinical tests (mice, pig, human skin samples) • For gold/tantalum particles: 50% injected dose for 2-20 mg • For weighed carbohydrate particles: 30-50% injected dose for 2 mg
Slide 37: Efficacy for vaccines
Efficacy for vaccines Epidermis is rich in antigen-presenting cells (APCs) (Langerhans cells). Elicits both antibody and CTL responses: • Dose reduction by a factor of 2.5-10 for conventional vaccines. • Dose reduction by a factor of 100-1000 for DNA vaccines. * as compared with IM needle injection.
Slide 38: DNA vaccine (Mice)
DNA vaccine (Mice) HBsAg DNA plasmid (Aldevron) in Balb-C mice Gold bead (n=6) vs. IM liquid delivery (n=4). Prime (7 mcg) at Day 0, Boost (10 mcg) at Day 28. Immune resmonses at 28 and 42 daaf'lls 5 -i-Avernge = 16600 4 =o 0 g'!Average=1510 3 0 0 2 Average ·.;a Average=21 0 28days 42days 28days 42d
Slide 39: DNA vaccine (Rabbit)
DNA vaccine (Rabbit) HBsAg DNA plasmid (Aldevron)in New Zealand White rabbit Gold bead (n=6)vs. lM liquid delivery (n=6)vs Inert Gold bead control (n=6). Prime (10 mcg )at Day 0, Boost (10 mcg) at Day 28 and Day 42. Immune responses at 0, 15, 29, 36 and 43 days Samplesdlluted1/500 ■ Group1(injo,ctor
Slide 40: Protein vaccine thermostability (Mice)
Protein vaccine thermostability (Mice) HBsAg protein {Aldevron) in Balb-C mice Thermostable formulation 10 mcg {nominal) (n=S)vs. Thermostable formulation 10 mcg ° (nominal) (11 months a t 22 c ) (n=6) vs. IM liquid delivery 10 mcg {control) (n=4). Prime a t Day 0, Boost a t Days 14 and 28. ■ Same r
Slide 41: Conventional vaccine efficacy (Mice)
Conventional vaccine efficacy (Mice) Powder vaccine delivery in mice {Influenza A/Aichi/68 H3N2- Charles River on trehalose particles) vs. SC liquid influenza vaccine+ TiterCold Max adjuvant (MF59). I oT o,from ind-.a1 ♦ • . t l l l l T.-•14....,. T-Oli!ll....,. ol o! T ol ° T c of n-:,:,::,u: T . :
Slide 42: Fast Response for Small Molecules
Fast Response for Small Molecules (animal trial '07) Systemic drug delivery (captopril powder in rats) - c o n t r o l Injection -x-Captoprl1 lnjeHon Tlme(mln) Fast response capability (comparable to IV injection)
Slide 43: Market opportunities
Market opportunities NuGen Powder Injector device + drug/vaccine = High value combination product: Added convenience for existing vaccines. Mass vaccination - e.g., Avian flu, HIV, SARS/Covid. New prophylactic vaccines. New therapeutic vaccines. Super-generics using off-patent drugs. Pat
NuGen Medical Devices — Technical Presentation (December 2020) on 6ix