KMG PHARMA LLC

Automated Microneedle Injector

for Intravitreal or Subconjunctival

Drug Delivery

2015

2015 KMG Pharma LLC

Automated Microneedle Injector

Key Features

Delivery of drugs into the intravitreal or subconjunctival spaces using low pressure jet injection equipped with a micro-needle that only penetrates into the sclera

Designed to be easily and precisely placed on the conjunctiva, particularly on the pars plana

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2015 KMG Pharma LLC

Automated Microneedle Injector

Advantages

Fast and precise positioning of the device on the conjunctiva, particularly on the pars plana, the area of predilection for intravitreal injection

Low risk of damage to the eye because the microneedle only penetrates into the sclera and because of precise positioning and stabilization of the device

Low risk of infection due to lack of direct penetration by the needle into the vitreous cavity

Short time required to execute the procedure because of the ease of use of the device

Potential improved user acceptance resulting from a shorter needle and the the reduced risk of ocular damage as compared to classic injection techniques

Potential to deliver a wide variety of conventional drugs, biopharmaceuticals, and microparticles

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2015 KMG Pharma LLC

Automated Microneedle Injector

Specs

Microneedle Length 0.1 – 1 mm. Gauge ≥ 27

Partial penetration into the sclera

Guide for the jet stream

Platform Made of soft elastomeric materials. 6 mm in diameter

Allows precise positioning on the pars plana

Adhesion and stabilization of the device on the conjunctiva

Drug reservoir Refillable cartridge

Disposable cartridge integrated with microneedle and platform

Jet injector Pressure ≤ 1000 psi

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2015 KMG Pharma LLC

Automated Microneedle Injector

Schematic View 5

2015 KMG Pharma LLC

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Intravitreal Automated Microneedle Injector

Application to the Pars Plana (Artist View)

Fluid flow

Micro-needle

Fluid flow

Microneedle

Pars plana

2015 KMG Pharma LLC

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Subconjunctival Automated Microneedle Injector

Application to the Conjunctiva (Artist View)

2015 KMG Pharma LLC

Automated Microneedle Injector

Activities Completed to Date

Lab prototype manufactured

Initial in vitro tests conducted in gelatin gels to

evaluate performance

Second series of tests conducted in

enucleated albino rabbit eyes

Study conducted ex vivo in albino rabbits

Study conducted in vivo in albino rabbits

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2015 KMG Pharma LLC

Automated Microneedle Injector

Lab Prototype 9

2015 KMG Pharma LLC

Ex Vivo Intraocular Injection of a Dye using an

Automated Microneedle Injector 10

Pressure Injection time Energy

psi s j Intravitreal Subconjunctival Wet

974 0.04 0.34 8 0 0

657 0.05 0.23 2 4 0

156 0.11 0.05 0 6 0

74 0.16 0.03 0 6 0

29 0.25 0.01 0 2 4

Number of injections

2015 KMG Pharma LLC

Representative Example of an Intravitreal Injection in an

Enucleated Rabbit Eye using an Automated Microneedle

Injector 11

f d

c b

e

a

Injection point

Injection point

Pre-injection Post-injection Post-injection

Post-dissection Post-dissection Post-dissection

Vitreous side Vitreous side Vitreous side

2015 KMG Pharma LLC

Representative Example of a Subconjunctival Injection in an

Enucleated Rabbit Eye using an Automated Microneedle

Injector 12

Post-injection Post-dissection

Vitreous side

2015 KMG Pharma LLC

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In Vivo Intraocular Injection of a Dye using an

Automated Microneedle Injector

Pressure Injection time Energy

psi s j Intravitreal Subconjunctival Wet

974 0.04 0.34 3 0 0

657 0.05 0.23 3 0 0

156 0.11 0.05 0 3 0

Number of injections

2015 KMG Pharma LLC

Rabbit Eye Following In Vivo Intravitreal Injection

of a Dye using an Automated Microneedle Injector

Control intravitreal injection using a 27 gauge

needle and syringe Cross section of frozen eye. Insert

shows the bluish injection area and a

black mark indicating the 12:00 o’clock

orientation

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2015 KMG Pharma LLC

Rabbit Eye Following In Vivo Subconjunctival Injection

of a Dye using an Automated Microneedle Injector

Control subconjunctival injection using a 27

gauge needle and syringe Cross section of frozen eye. Insert

shows the bluish injection area

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2015 KMG Pharma LLC

Histology (H&E) of Rabbit Eyes Following In Vivo

Intravitreal or Subconjunctival Injection using an

Microneedle Automated Injector 16

Microneedle

injector

(974 psi)

Microneedle

injector (156 psi)

Control (Syringe/27 g needle)

Control (Syringe/27 g needle)

Intravitreal injection Subconjunctival injection

2015 KMG Pharma LLC

Automated Microneedle Injector

Conclusions

Placement of the edge of the platform at the location of the corneoscleral limbus allows precise positioning and application of the microneedle to the pars plana area

A microneedle that penetrates partly through the sclera allows use of relatively low pressures for intravitreal delivery (1000 vs. 4000 psi for conventional jet injection).

Subconjunctival delivery can be achieved successfully with the same device using lower pressures (100 psi)

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2015 KMG Pharma LLC

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Automated Microneedle Injector

Intellectual Property

Issued US patent 7,678,078 (WO2010047753) gives KMG

Pharma exclusive right for an intraocular automated

injector (injection pressures between 50–1000 psi)

comprising a microneedle (0.1-1 mm) and a positioning

platform.

2015 KMG Pharma LLC

Automated Microneedle Injector

Competitive Landscape

So far, no specific devices for intravitreal injection have

been developed and vitreoretinal specialists rely on

conventional syringes and needles.

No devices have been patented/developed for

subconjunctival injection.

A number of companies are attempting to develop

intraocular implants (Bausch &Lomb) or controlled

release formulations (SurModics) for the long term

delivery of drugs into the intravitreal cavity. So far, no

implants or CR formulations have been developed for

biopharmaceuticals.

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2015 KMG Pharma LLC

Automated Microneedle Injector

Market Potential

Large and growing patient population with ocular diseases susceptible

to anti-VEGF therapy (anti-VEGF antibodies, VEGF trap, anti-VEGF

aptamer) that may require intraocular injections.

a http://www.nei.nih.gov/eyedata/

b CMRO, 26, 1587, 2010

c Arch Ophthalmol 126, 513 2008

d Frost and Sullivan: US Leading Ophthalmic Diseases Report

e Diabetic Macular Edema Review Article on the the Digital Journal of Ophthalmology from Harvard University and the

American Diabetes Association

f RBC Capital Markets

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Prevalence

(million)

Incidence

(000 per year)

Growth Rate

(% per year)

Advanced Age-related Macular Degeneration 1.8a 240d 1.6d

Diabetic Macular Edema 1.5b 190e 5e

Central Retinal Vein Occlusion 1.5c 95f TBD

U.S. Population Data

Disease

2015 KMG Pharma LLC

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Automated Microneedle Injector

Drug Device Potential

Rights for US Patent 7083802 secured by KMG Pharma.

This issued US patent claims intraocular (intravitreal and

subconjunctival) injection of Rapamycin or Ascomycin or

Cyclosporin A or Tacrolimus for the treatment of diabetic

retinopathy, retinitis pigmentosa, and age related

macular degeneration. These drugs can be developed

by KMG Pharma for conventional intraocular injection or

in conjunction with KMG Pharma devices.

Other biopharmaceutical drugs of interest can be

developed with KMG Pharma devices.

KMG PHARMA LLC

An expert ophthalmic incubator company