Del iver ing Invest igat ional Gene Therapy, GT005, v ia the Orbi t™ Subret inal Del ivery System in the Phase I / I I FOCUS Cl in ical Tr ia l

Excerpted from Presentat ion: “De l ivery St ra teg ies for Gene and Cel l Therap ies in Ret ina l D isease”

A m e r i c a n A c a d e m y o f O p h t h a l m o l o g y ( A A O ) R e t i n a S u b s p e c i a l t y D a y

1 3 N o ve m b e r 2 0 2 1

A l l e n C H o , M D

2

*Orbit SDSTM is indicated in the United States for microinjection into the subretinal space. The 510(k) clearance is based upon the use

of Balanced Salt Solution (BSS or BSS PLUS). Gyroscope is evaluating delivery of its investigational gene therapy, GT005, using the

Orbit SDSTM in its clinical development program.

The OrbitTM Subretinal Delivery System*

Designed for Precision and Scalability for Surgical Delivery

• The Orbit SDSTM accesses the subretinal space via a suprachoroidal approach

• Cannulation of the suprachoroidal space with a flexible cannula

• SDS cannula and microneedle are advanced into the subretinal space to enable targeted dose delivery, without the need for a vitrectomy or a retinotomy

© Gyroscope Therapeutics Limited, 2021

• CFI’s primary function is to keep

the complement system in balance

and to sequester away C3 thereby

removing it from the alternative

pathway amplification loop1

• Ba is a direct readout of the

amplification loop†

• C3 breakdown products can also

be measured to indicate inhibition

of the complement system

CFI Restores Balance to Overactive Complement System1

†It is unclear whether the relationship between Ba levels and lytic activity is linear.

1. Lachmann PJ. The story of complement factor I. Immunobiology. 2019;224(4):511‐517..

© Gyroscope Therapeutics Limited, 2021

Cell lysis and death

C3

C3b

C5

MAC

Classical Pathway Lectin Pathway Alternative Pathway

CFHCFI

iC3b

C3c

Ba

Ba Ba

BaBa

+ C3d CR1 + CFI

CFH + CFI

Amplification Loop

Degradation

CFB CFD

Adapted from Anderson DH, Radeke MJ, Gallo NB, et al. The pivotal role of the complement system in aging and age-related macular

degeneration: hypothesis re-visited. Prog Retin Eye Res. 2010;29(2):95-112.

3

Transvitreal Delivery of Subretinal Gene TherapyDelivery of Gene Therapy with

OrbitTM Subretinal Delivery System

Dose Escalation

Dosing complete

Dose Expansion

Dosing complete

Dose Escalation

Dosing complete

Dose Expansion

Enrolling

Phase I/II Open-Label GT005 Safety and Dose Response Trial

Cohort 1

2E10 vg

Cohort 2

5E10 vg

Cohort 3

2E11 vg

Cohort 4

5E10 vg

2E11 vg

Cohort 5

5E10 vg

Cohort 6

2E11 vg

n = 20

n = 3

n = 3n = 4

n = 4

n = 3

Cohort 7

2E11 vg

n = up to 20

Safety Evaluation(after 3 participants complete 5 weeks follow-up)

Goals: Evaluate Safety, Protein Expression, Complement Modulation

© Gyroscope Therapeutics Limited, 2021 4

2nd Generation Device

© Gyroscope Therapeutics Limited, 2021

Improved ErgonomicsFlexible pad with adhesive

backing serves as a platform for

the Subretinal Injection Device

Flexible Cannula More flexible than 1st gen

MicroneedleRefined geometry to improve

ease of bleb creation

Needle Advancement KnobKnob allows for sub-millimeter control

over needle advancement

Precise DosageDose syringe engineered to

provide a repeatable volume

5

Surgical 2D Bleb Mapping

Bleb Location Composite

ODOS

6

3D Intraoperative OCT

Precision Dosing Orbit SDS

7