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.
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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
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Surgical 2D Bleb Mapping
Bleb Location Composite
ODOS
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3D Intraoperative OCT
Precision Dosing Orbit SDS
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