A Quick Peek into the FutureGlaucoma Therapeutic Innovations

Ike K Ahmed MD GoEyeCare Trillium Health Partners University of Toronto

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IK Ahmed MD

DisclosuresAdeTherapeutics: C Accelerated Vision: C ACE Vision Group: C Alcon: C, R AMO: C, R, S Aerie: C Allergan: C, R Aquesys: C, R Bausch & Lomb: C Carl Zeiss: C, R, S Clarity Medical Systems: C Croma Pharma: C Envisia Therapeutics: C Eyelight: C ForSight Labs: C

Glaukos: C, R, S InnFocus: C Iridex: C, R Ivantis: C, R, S LayerBio: C New World Medical: R Omega Ophthalmics: C ONO Pharma: C PolyActiva: C Sanoculis: C Science Based Health: C SOLX: C, R Stroma: C Transcend: C, R TrueVision: C

C = Consultant R = Research Support

S = Speakers Honorarium

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IK Ahmed MD

Therapeutics Drug Delivery

MIGS

Neuroprotection Regeneration

Diagnostics Early Detection

Progression IOP Telemetry

I n n o v a t i o n S p a n

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IkeKAhmedMD

OcularSurface

SustainedReleaseApproaches

Intravitreal

Suprachoroidal

SubconjunctivalScleral

AnteriorChamber

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IkeKAhmedMD

Latanoprost-ElutingContactLens

• Toaddresspoorcompliance

• PreservativeFree

• Canbemadewithrefractive

errorcorrection

• Sustained,controlleddelivery

• Therapeuticpayload

• Durationof2weeksor1month

• Couldbeusedasacontinuous

wearlensDr.JosephB.Ciolino,Dr.DanielS.Kohane

MassachusettsEyeandEarInfirmary,MIT,BostonChildren’sHospital

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IkeKAhmedMD

Drug-ElutingPunctalPlugSystem MatiTherapeutics

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Drug-ElutingPunctalPlugs&InjectableDepots

• Drug-elutingpunctumplugs

– Biodegradablemicrospheresinhydrogel– Travoprostdrugrelease=2-3months– Comfortandretentionupto3months

• ReSure®Sealant

– Insituforminghydrogelbarrier– Localizedincisionprotectionfromfluidegress– Preparedandappliedinlessthan30seconds

• Drug-elutinginjectabledepots

– 4-6monthssustainedrelease–anti-VEGF*– Intraocularbiocompatibilityandlocalization– 30gaugeneedleintravitrealinjectability

OcularTherapeutix

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IK Ahmed MD

Forsight Vision5 Helios Insert

• Fornix ocular insert

• Bimatoprost elution

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Collagen added to NaCl

<1 minute after

InsituPolymerizableCollagenSolutionEuclidSystemsCorp

• Injectableviscousformssolidgel

drugdepotwhenexposedto

physiologicalfluidsorinjectedinto

tissueswithin60seconds

• SubconjunctivaIinjection

• Latanoprostgel=>1month

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IkeKAhmedMD

ImplantableCollagenFilms/WafersEuclidSystemsCorp

• Biodegradablefilmcanbe

preparedtodegradefrom

minutesto>6months

• Subconjunctivalinjection

• Latanoprostcollagenwafer

showedsustainedreleasefor

180dayswithminimalburst

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Day 1

Day 7

Day 14

Bioerodibleimplantvisibly

decreasinginsizeover

time

Nosignofadverse

responsetoimplant

Photographsofarabbiteyeupto14days

Drug-PolymerConjugateImplant PolyActivia

Subconjuntivalor

intravitreal21Ginjection

Combinationdrugs

3-6mosduration

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PRINTDexamethasonePLGAimplants:

2.24μg/implant(17.5%w/w)

Implants• Extendedreleaseformulationsofbiologics

andsmallmoleculedrugs

• Reproducibleimplantsize,shape,

compositionanddose

• Simpledelivery

Micro/NanoParticles• Topicaldeliverywithfewerdoses

• Sustainedrelease

• Permeationandtargetedtoincreaseefficacy

LowmodulusPRINTmonodisperse

microparticles

“PRINT”EngineeredNanoparticlesEnvisiaTherapeutics

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IkeKAhmedMD

Intracameral(Day12)PRINTFormulation#7

Subconjuctival(Day12)PRINTFormulation#7

Intracameralinjections(1implant/eye)Formulation#7:250μmx250μmx1,500μm

drugimplant

Subconjuctivalinjections(1implant/eye)Formulation#7:250μmx250μmx1,500μm

drugimplant.

Preliminarystudiesdemonstratesuccessfulintravitreal,intracameralandsubconjuctivalinjectionswithPRINTimplantsinrabbitsNopost-insertionadverseeffectsobserved

“PRINT”EngineeredNanoparticlesEnvisiaTherapeutics

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AllerganBimatoprostSRIntracameralBioerodibleDrugPellet

Abioerodible,extended-releasedrugpelletthatcanbeadministeredviainjectionwithasmallgaugeneedle-injectortothefrontoftheeye

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ReplenishOphthalmicMicroPump

• Subconjunctivalimplant

• Injectprogrammedamountof

drugatsettimes

• MEMSdevice

• 12monthdrugsupply

• Refilledwith31Gneedle

• Rechargewirelessly

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IK Ahmed MD

Intravitreal Encapsulated Cell Therapy

2015-04-25, 1:22 AMEncapsulated Cell Technology-ECT | Nuerotech Pharmaceuticals

Page 1 of 2http://www.neurotechusa.com/ect-platform.html

Watch ECT Principles Video

Watch ECT Design Video

Watch ECT Implantation Video

ECT PlatformNeurotech’s patented core technology platform, Encapsulated Cell Therapy (ECT), is a first-in-class, versatiledrug delivery platform in development for the treatment of a broad array of eye diseases. ECT is a geneticallyengineered ocular implant that enables continuous production of therapeutic proteins to the eye for over 2years. Additionally, the therapy is reversible by simply removing the implant.

The ECT implant is inserted into the vitreous through a single incision and sutured in place in a 20-minuteoutpatient surgical procedure. Watch Video.

ECT implants been successfully implanted in over 400 subjects for up to 5 years duration.

Customized Therapeutic Cell Line

The basis of the ECT platform is the customized NTC-200 cell line, a proprietary cell line derived from normalhuman retinal pigment epithelial cells. NTC-200 cells were initially screened from many other cell types asbeing remarkably hardy: the cells thrive under low oxygen and low nutrient conditions, while being amenable togenetic manipulations under stringent selection methods. Recombinant cell lines derived from transfectedNTC-200 cells are able to secrete major classes of therapeutics, including antibodies, fusion proteins, andgrowth factors. Cell lines are isolated from the host inside a sealed polymer device.

Versatile Platform

The ECT device is fabricated from medical-grade plastics and consists of a semi-permeable exterior capsuleand internal scaffolding, which allows for controlled cell growth and continuous protein production within thecartridge. Watch Video

The semi-permeability of the ECT capsule allows oxygen and nutrients in the vitreous to freely diffuse inward,and allows therapeutic to freely diffuse outward. Different device geometries and nutrient conditioning areexplored for each clinical cell line produced, and the configuration best addressing the target disease aretested in models for bio-compatibility. Watch Video

The versatility of the ECT device enables long-term and continuous targeted delivery of single and combinationtherapeutics, both internally developed at Neurotech, as well as those developed by potential partners forfuture collaboration.

Dedicated Manufacturing

Neurotech’s dedicated, in-house manufacturing operations, located at their corporate headquarters inCumberland, RI, are held within a 26,000 square foot facility and operate under GMP guidelines. The ECTmanufacturing facility is designed for clinical development and commercial launch, with the capacity ofproducing at least 150,000 ECT units a year. Cells are inserted into ECT devices in a controlled environmentby proprietary semi-automated liquid injectors and performed under cGMP clean room environments. Finishedimplants are held in nutrient media containers and monitored under strict cGMP quality guidelines. ECTimplants are then shipped to trained ophthalmic surgeons for implantation into patients.

Privacy Policy © 2014-2015 Neurotech

NEWS UPDATE

Find out about the latest news at Neurotech.

Home | About Neurotech | Platform & Pipeline | Newsroom | Contact

ECT Platform ECT Pipeline NT-503 ECT NT-506 ECT NT-501 ECT

About Neurotech Platform & Pipeline Newsroom Contact

2015-04-25, 1:22 AMEncapsulated Cell Technology-ECT | Nuerotech Pharmaceuticals

Page 1 of 2http://www.neurotechusa.com/ect-platform.html

Watch ECT Principles Video

Watch ECT Design Video

Watch ECT Implantation Video

ECT PlatformNeurotech’s patented core technology platform, Encapsulated Cell Therapy (ECT), is a first-in-class, versatiledrug delivery platform in development for the treatment of a broad array of eye diseases. ECT is a geneticallyengineered ocular implant that enables continuous production of therapeutic proteins to the eye for over 2years. Additionally, the therapy is reversible by simply removing the implant.

The ECT implant is inserted into the vitreous through a single incision and sutured in place in a 20-minuteoutpatient surgical procedure. Watch Video.

ECT implants been successfully implanted in over 400 subjects for up to 5 years duration.

Customized Therapeutic Cell Line

The basis of the ECT platform is the customized NTC-200 cell line, a proprietary cell line derived from normalhuman retinal pigment epithelial cells. NTC-200 cells were initially screened from many other cell types asbeing remarkably hardy: the cells thrive under low oxygen and low nutrient conditions, while being amenable togenetic manipulations under stringent selection methods. Recombinant cell lines derived from transfectedNTC-200 cells are able to secrete major classes of therapeutics, including antibodies, fusion proteins, andgrowth factors. Cell lines are isolated from the host inside a sealed polymer device.

Versatile Platform

The ECT device is fabricated from medical-grade plastics and consists of a semi-permeable exterior capsuleand internal scaffolding, which allows for controlled cell growth and continuous protein production within thecartridge. Watch Video

The semi-permeability of the ECT capsule allows oxygen and nutrients in the vitreous to freely diffuse inward,and allows therapeutic to freely diffuse outward. Different device geometries and nutrient conditioning areexplored for each clinical cell line produced, and the configuration best addressing the target disease aretested in models for bio-compatibility. Watch Video

The versatility of the ECT device enables long-term and continuous targeted delivery of single and combinationtherapeutics, both internally developed at Neurotech, as well as those developed by potential partners forfuture collaboration.

Dedicated Manufacturing

Neurotech’s dedicated, in-house manufacturing operations, located at their corporate headquarters inCumberland, RI, are held within a 26,000 square foot facility and operate under GMP guidelines. The ECTmanufacturing facility is designed for clinical development and commercial launch, with the capacity ofproducing at least 150,000 ECT units a year. Cells are inserted into ECT devices in a controlled environmentby proprietary semi-automated liquid injectors and performed under cGMP clean room environments. Finishedimplants are held in nutrient media containers and monitored under strict cGMP quality guidelines. ECTimplants are then shipped to trained ophthalmic surgeons for implantation into patients.

Privacy Policy © 2014-2015 Neurotech

NEWS UPDATE

Find out about the latest news at Neurotech.

Home | About Neurotech | Platform & Pipeline | Newsroom | Contact

ECT Platform ECT Pipeline NT-503 ECT NT-506 ECT NT-501 ECT

About Neurotech Platform & Pipeline Newsroom Contact

2015-04-25, 1:22 AMEncapsulated Cell Technology-ECT | Nuerotech Pharmaceuticals

Page 1 of 2http://www.neurotechusa.com/ect-platform.html

Watch ECT Principles Video

Watch ECT Design Video

Watch ECT Implantation Video

ECT PlatformNeurotech’s patented core technology platform, Encapsulated Cell Therapy (ECT), is a first-in-class, versatiledrug delivery platform in development for the treatment of a broad array of eye diseases. ECT is a geneticallyengineered ocular implant that enables continuous production of therapeutic proteins to the eye for over 2years. Additionally, the therapy is reversible by simply removing the implant.

The ECT implant is inserted into the vitreous through a single incision and sutured in place in a 20-minuteoutpatient surgical procedure. Watch Video.

ECT implants been successfully implanted in over 400 subjects for up to 5 years duration.

Customized Therapeutic Cell Line

The basis of the ECT platform is the customized NTC-200 cell line, a proprietary cell line derived from normalhuman retinal pigment epithelial cells. NTC-200 cells were initially screened from many other cell types asbeing remarkably hardy: the cells thrive under low oxygen and low nutrient conditions, while being amenable togenetic manipulations under stringent selection methods. Recombinant cell lines derived from transfectedNTC-200 cells are able to secrete major classes of therapeutics, including antibodies, fusion proteins, andgrowth factors. Cell lines are isolated from the host inside a sealed polymer device.

Versatile Platform

The ECT device is fabricated from medical-grade plastics and consists of a semi-permeable exterior capsuleand internal scaffolding, which allows for controlled cell growth and continuous protein production within thecartridge. Watch Video

The semi-permeability of the ECT capsule allows oxygen and nutrients in the vitreous to freely diffuse inward,and allows therapeutic to freely diffuse outward. Different device geometries and nutrient conditioning areexplored for each clinical cell line produced, and the configuration best addressing the target disease aretested in models for bio-compatibility. Watch Video

The versatility of the ECT device enables long-term and continuous targeted delivery of single and combinationtherapeutics, both internally developed at Neurotech, as well as those developed by potential partners forfuture collaboration.

Dedicated Manufacturing

Neurotech’s dedicated, in-house manufacturing operations, located at their corporate headquarters inCumberland, RI, are held within a 26,000 square foot facility and operate under GMP guidelines. The ECTmanufacturing facility is designed for clinical development and commercial launch, with the capacity ofproducing at least 150,000 ECT units a year. Cells are inserted into ECT devices in a controlled environmentby proprietary semi-automated liquid injectors and performed under cGMP clean room environments. Finishedimplants are held in nutrient media containers and monitored under strict cGMP quality guidelines. ECTimplants are then shipped to trained ophthalmic surgeons for implantation into patients.

Privacy Policy © 2014-2015 Neurotech

NEWS UPDATE

Find out about the latest news at Neurotech.

Home | About Neurotech | Platform & Pipeline | Newsroom | Contact

ECT Platform ECT Pipeline NT-503 ECT NT-506 ECT NT-501 ECT

About Neurotech Platform & Pipeline Newsroom Contact

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IK Ahmed MD

Microinvasive Glaucoma Surgery• Ab-interno approach

• Minimally traumatic

• At least modest efficacy

• Extremely high safety profile

• Rapid recovery

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IK Ahmed MD

iStent iStent inject Hydrus

Cypass iStent supra Xen

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IK Ahmed MD

Suprachoroidal Micro-StentTranscend CyPass Micro-Stent

Investigational device. Not approved by the FDA.

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IK Ahmed MD

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IK Ahmed MD

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IK Ahmed MD

AqueSys XEN Implant Generations

Investigational device. Not approved by the FDA.

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IK Ahmed MD

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IK Ahmed MDIOP 12

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IK Ahmed MD

Glaucoma Treatment Algorithm

1 Med Multiple Meds SLT Multiple

Meds Trab 2nd Trab or Tube

1 Med SLT

Drug Delivery MIGS MIGS2 Trab

or Tube

Phaco + MIGS

Now & Potentially in 5 years

Level of Invasiveness

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