Neurotech

DELIVERING TRANSFORMATIVE THERAPIES FOR CHRONIC EYE DISEASES Quinton Oswald | President and CEO

OC TOB E R 1 6 , 2 0 1 4

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We Are Experienced Leaders and Investors in Ophthalmics

Unique CombinaMon of ReMnal Industry,

Clinical and Regulatory ExperMse

QUINTON OSWALD President and CEO

RHETT SCHIFFMAN, MD, MS, MHSA CMO

RICHARD SMALL CFO and VP Finance

KONRAD KAUPER, MS VP Core Technology Development

CytoTherapeuMcs

CAHIL MCGOVERN, PhD VP Manufacturing CytoTherapeuMcs

TERRY DAGNON VP Regulatory

JAMES MAZZO

EUGENE DE JUAN

BRYANT FONG

DAVID FUCHS LFG

LESTER KAPLAN, PhD

WILLIAM LINK, PhD

BOARD

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Wet AMD: Are “Real World” Treatment Frequencies Enough? Studies indicate dosing is less than op1mal

1. Campbell et al. Program #3065, Presented at ARVO 2014. 2. Lad EM, et al.. Am J Ophthalmol. 2014;158(3):537-543. 3. Kiss S, et al. OSLI Retina. 2014;45(4):285-291.

Study PopulaMon

InjecMon DuraMon

Mean InjecMon Rate

RetrospecSve EMR Analysis in DME1 103 eyes 1 year 2.7

UNVEIL1 505 (396 lost to follow-‐up) 1 year 3.9

Medicare Analysis2 459,237 1 year 4.3

LUMINOUS1 2,112 1 year 5.2

RetrospecSve Claims Analysis3 11,688 1 year 4.5 – 6.8

RetrospecSve Claims Analysis4 19,026 1 year 4.6 – 6.9

HELIOS5 267 2 years 7.6

SEVEN-‐UP6 65 3.4 years 6.8

4. Campbell et al. Program #3065, Presented at ARVO 2014. 5. Lad EM, et al.. Am J Ophthalmol. 2014;158(3):537-543. 6. Kiss S, et al. OSLI Retina. 2014;45(4):285-291.

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Neurotech: Developing a TransformaSve Drug Delivery Plaborm

VersaMle Pla`orm to Treat Broad Array of Eye Diseases

1st in Class Pla`orm for CONTINUOUS PRODUCTION OF THERAPEUTIC PROTEINS IN EYE

Encapsulated Cell Therapy (ECT)

LEAD PRODUCT NT-‐503 FOR WET AMD

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Macro Trends Driving Large Markets

AGING + DIABETES FUELING PATIENT NEED

Sources: Datamonitor 2014, EvaluatePharma, BioMed Tracker, Cowen TherapeuMc Outlook, medscape.org

$1.5

$2.1

$3.3 $3.3 $3.6

$3.9 $4.2

$4.5 $4.9

$5.2

2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

#1 Cause of Visual

Impairment in Adults with

Type II Diabetes

~190K U.S. PopulaMon

DIABETIC MACULAR EDEMA

(DME)

#1 Cause of Blindness Over Age 55

~340K U.S. PopulaMon

WET AGE-‐RELATED MACULAR

DEGENERATION (WET AMD)

U.S. Revenue EsMmates ($ Billions)

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100+ Back of the Eye Rx Products in R&D

Which Will Require Back of the Eye Delivery

INNOVATION ACROSS CNV PATHOPHYSIOLOGY STAGES STIMULATION OF

ANGIOGENIC SIGNALING

OxidaMve Stress

PKC Pathway

Inflammatory Mediators

Lipofuscin AccumulaMon

Hyperglycemia

•  Protein AccumulaMon Inhibitor •  Complement Inhibitors (4) •  CorMcosteroids (9) •  Cytokine/Interleukin Inhib. (4) •  NSAIDs (2) •  TNF Inhibitors (4) •  Other Immunomodulators (9) •  OxidaMve Stress Inhibitors (4) •  Visual Cycle Modulator •  Insulin Receptor Inhibitor •  Kallikrein Inhibitors (2) •  PKC Inhibitors (2)

PRO-‐ANGIOGENIC SIGNALING PATHWAYS

↑ IGF

↑ VEGF ↑ PDGF

↑ FGF

↑ AngiopoieMn

•  VEGF Inhibitors (17) •  VEGF/PDGF Inhibitors (3) •  PDGF Inhibitors (3) •  FGF Inhibitor •  MulMkinase Inhibitors (3) •  AngiopoieMn Inhibitors (2)

NeovascularizaMon and Permeability Increases

VASCULAR PATHOPHYSIOLOGY

•  Integrin Inhibitors (2) •  PI3K/mTOR Inhibitors (3) •  Other AnM-‐Sngiogenic (17) •  Vascular DisrupMng Agents (3) •  Photodynamic Therapy (2) •  Vascular Permeability Inhibitor

DOWNSTREAM PATHOPHYSIOLOGY

Vision Loss

Fibrosis à ReMnal Detachment

•  AnMfibroMc •  Stem Cell Therapies (5)

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Requirements for EffecSve Intra-‐Ocular Drug Delivery System

We Have Created a Unique SoluMon to Address Unmet Needs

EXTERNAL OCULAR PUMP

IVT GENE THERAPY

IVT IMPLANT NEUROTECH ECT

Single and MulS-‐Factor CombinaSons

PaSent Ease / Compliance

Reversibility

Long-‐Term Efficacy / DuraSon 4-‐6 Months >12 Months 1-‐2 Years

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Well-‐Validated Intravitreal Implant Approach

ReMsert® 3-‐YEAR TREATMENT DURATION FOR SMALL MOLECULES

Proven Surgical Paradigm Unmet Need for Large Protein Molecules

Figure From

Bausch + Lomb

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OUR DIFFERENTIATED PLATFORM: ECT

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Encapsulated Cell Therapy Is an Intraocular Drug Factory

Miniaturized Bioreactor

PRODUCING LONG-‐TERM CONTINUOUS THERAPEUTIC

PROTEIN DELIVERY

NO IMMUNE SYSTEM IMPACT

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Flexible Cartridge Design

MULTIPLE CONFIGURATIONS FOR CUSTOMIZED DELIVERY ECT 1 ECT 2 ECT 3

External Diameter (mm) 1.1 1.1 2.2

Membranes/Cartridge Single Single MulMple -‐ 3-‐8

AcSve Length (mm) 6.0 8.5 10

Incision Size (mm) 2.0 2.0 3.0

Release Rate (μg/d) 0.3 – 0.5 2.0 -‐ 2.5 10 -‐ 12

INNOVATIVE DESIGN FOR EFFICACY AND EASE OF IMPLANT/EXPLANT Single Membrane Implant MulMple Membrane Implant

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DEMONSTRATED EFFICACY WITH CLEAR CLINICAL AND REGULATORY PATH FOR NT-‐503

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Efficacy Snapshot: Visual Improvement and Decreased ReSnal Thickness PATIENT A2301: 76 YEAR OLD WOMAN – ECT 2 DOUBLE IMPLANT

+25 Leser Vision Gain and ~350µ Decrease in

Central Foveal Thickness

Baseline 40 Lesers / 639 um

1 Month 46 Lesers / 355 um

2 Months 50 Lesers / 295 um







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Clinical Proof of Concept -‐ PP PopulaSon Data Censored for Missed Visit and all Subsequent Visits for PaSents Receiving Rescue

+13 LETTERS / -‐207µ AT MONTH 12 (ECT 2 X 2)

Single ECT 2 Implant (2.0 -‐ 2.5 μg/day) Double ECT 2 Implants (4.0 -‐ 5.0 µg/day)

Central ReMnal Thickness ETDRS Visual Acuity Median Change From Baseline (±SEM) Median Change From Baseline (±SEM)

Doubling in Release Leads to 2-‐3x Increase in Effect

Months Months

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Good Safety Profile

No AE’s Leading to DisconMnuaMon

Most AEs Asributed to Surgical Procedure, Concurrent Ocular CondiMons or Unrelated CondiMons

No Treatment-‐Related Cataract or InfecMous EndophthalmiMs

•  No Post-‐Op Steroid Coverage (Protocol DeviaMon) •  Resolved Without Sequelae

One Related SAE – Sterile EndophthalmiMs

ECT 1 and 2, SINGLE AND DOUBLE IMPLANTS

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NT-‐503 MulSple Membrane ECT 3 Provides Increased Daily Delivery Rates of VEGFR

2-‐3x Increase

Compared to Release Rates of ECT 2 Double Implants

0

2000

4000

6000

8000

10000

12000

14000

VEGFR Levels µg/day

0

4

8

12

10

6

2

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ECT 1 (Single Implant)

ECT 2 (Single Implant)

ECT 2 (Double Implants)

ECT 3 (Single Implant with MulSple Membranes)

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150 PaSent Phase 2 to IniSate 1Q 2015: Recurrent/Persistent Wet AMD

Single Intravitreal ImplantaMon of NT-‐503 ECT 3

vs. Eylea® (Aflibercept)

Injected Intravitreally Every 8 Weeks

Randomized, Controlled, Masked Trial to Compare Safety and Efficacy Over 12 Months With 12 Month Follow Up

in Preserving Vision in PaMents Who Have Been Previously Treated and Responded to at Least 3 AnM-‐VEGF InjecMons and SMll Have AcMve Disease

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Clear Clinical-‐Regulatory Pathway to CommercializaSon PRE-‐IND MEETING HELD: FDA OFFICE OF CELL AND GENE THERAPY ON MARCH 28, 2014

CMC: Including Device and Cell-‐Based Components

Non-‐Clinical GLP Program

Phase 2 and Phase 3 Study Designs

Proposed Plans Were Considered Acceptable Covering All Aspects of Development

DELIVERING TRANSFORMATIVE THERAPIES FOR CHRONIC EYE DISEASES

Date post:	14-Apr-2017
Category:	Healthcare
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