GB-102 Clinical UpdateIs Every 6 Month IVT Dosing in Wet AMD Achievable?

Charles P. Semba, MD, FACC, FACRChief Medical Officer

O c t o b e r 2 5 , 2 0 1 8

| C O N F I D E N T I A L A N D P R O P R I E T A R Y2

Focus on Extended Duration Dosing Can 6 Month Dosing Intervals (or Longer) Be Achieved in Wet AMD?

Reducing Treatment Burden

for Patients and Physicians

Opportunity

GB-102:

Q6 M Dosing in wet AMD with IVT

Depot Formulation of Sunitinib

Lead

GB-103:

Q12 M Dosing in Retina

GB-201:

Q4 - 6 M Dosing in Glaucoma

Pipeline

Bioabsorbable Microparticle

Delivery to Enable Sustained Drug

Release For Up to 12 Months

Technology

Clinical-stage Venture-based Ophthalmology

Biotech

Company

| C O N F I D E N T I A L A N D P R O P R I E T A R Y3

GB-102 - Depot Technology

GB-102PLGA/10% sunitinib

microparticles

BufferedHyaluronate

Step 1 Reconstitution

Step 3 Drug Release into RPE/Choroid

Sunitinib releaseDepot

PLGA (poly-(lactic-co-glycolic acid))

H2O

Lactic acid / glycolic acid

• PLGA used in dissolvable sutures• Biodegrades / bioabsorbs• Tunable drug delivery• Depot ~5 mm in size

Surface treated to promote aggregation

Step 2 IVT Injection / Bioabsorbable

27 g needle 50 μL

CNV Lesion

Depot

DAY 8 DAY 92

Mini-Pig

Day 8 Day 92

| C O N F I D E N T I A L A N D P R O P R I E T A R Y4

GB-102: Sunitinib is a Potent Anti-Angiogenic

VEGFReceptor 1

VEGFReceptor 2

VEGFReceptor 3

GB-102 (Sunitinib)

Inhibits All VEGF Receptors

VEGF-DVEGF-A VEGF-B VEGF-C

• Multiple receptor tyrosine kinase inhibitor• Approved oral agent for solid tumors (SUTENT)• First proposed for nAMD in 2006

AfliberceptBevacizumabBrolucizumabRanibizumab

(Takahashi 2006)

| C O N F I D E N T I A L A N D P R O P R I E T A R Y5

0

0.005

0.01

0.015

0.02

0.025

0.03

0.5M 2M 3.5M 5M 6M

GB-102: Pre-clinical Evidence of 6 Month Durability from Single IVT Dose

10

1

0.1

0.01

102

103

104

105

106

2 4 6Months

Suni

tinib

(ng/

mg)

RPE/Choroid

Retina

Vitreous

1 3 5 7

Ki VEGFR

Rabbit Tissue Drug Level of SunitinibSingle Injection 1 mg IVT GB-102

No Effect Range (Placebo)

Mouse Laser CNV ModelAflibercept vs. GB-102

* *

* p<0.05 (GB-102 or aflibercept vs. fellow eye control)

Day 0: • Aflibercept x 1 dose IVT • GB-102 x 1 dose IVT

* *Mea

n CN

V Ar

ea (m

m2 )

Months(Campochiaro 2018)

Sunitinib has high affinity for melanin

binding

No detectable plasma drug levels in GLP studies

GB-102

aflibercept

*

| C O N F I D E N T I A L A N D P R O P R I E T A R Y6

GB-102 - Target Product Profile

Unmet Need Reduce treatment burden in wet AMD

Efficacy Non-inferior to aflibercept Q 8 wks

Dosing/Schedule IVT Q 6 months using 27 g needle

Safety Similar to approved agents

Depot Bioabsorbable / no inflammation

Decrease injection frequency to twice per year

1 Confidential

Wet AMD – Key Challenges in the anti-VEGF Era Burden of Care is Growing at 10% Per Year

In 2016, an estimated 6 million IVT will be performed in US to manage AMD

Williams G (2014)

2000 02 04 06 08 10 12 14 2016

2M

4M

6M

Intravitreal Injections and Cataract Procedures in the United States by Year

IVT

Cataract

2000 02 04 06 08 10 12 14 16

2M

4M

6M IVT

Cataract

Rapid Rise in IVT Injections(2000 - 2016)

(Williams 2014)

| C O N F I D E N T I A L A N D P R O P R I E T A R Y7

Phase 1 (ADAGIO Study) - First-in-Human Trial of GB-102Wet AMD Subjects Who Have at Least 3 Prior Injections of Anti-VEGF

2 mg GB-102 N=8

1 mg GB-102 N=8

0.5 mg GB-102 N=8

0.25 mg GB-102 N=8

Single Injection

Monthly Visits for 8M

GOALS

• Safety • Durability Profile• Pharmacodynamics

• Visual acuity (eyechart)• Retinal thickness (OCT)

• Systemic Exposure

Topline (6 to 8 Month) Data Will Be Presented at Hawaiian Eye / Retina 2019January 21, 2019 - Dr. David Boyer, MD

| C O N F I D E N T I A L A N D P R O P R I E T A R Y8

• Clinical stage company - completing first-in-human, Phase 1 GB-102 safety/durability study (ADAGIO)

• GB-102 topline data presentation - Hawaiian Eye/ Retina January 2019 - Can 6 Month Dosing Be Achieved?

• Phase 2 study (PRELUDE) in development - commencing 2H 2019

• Pipeline programs for GB-103 (once per year) and GB-201 (glaucoma) in progress

Reducing Treatment Burden

for Patients and Physicians

Opportunity

GB-102: Q6 M Dosing in wet

AMD with IVT Depot Formulation

of Sunitinib

Lead

GB-103: Q12 M Dosing in

Retina

GB-201:Q4 - 6 M Dosing in

Glaucoma

Pipeline

Bioabsorbable Microparticle

Delivery to Enable Sustained Drug

Release For Up to 12 Months

Technology

Clinical-stage Venture-based Ophthalmology

Biotech

Company

Thank You!