Table 2.

Clinical trial data for OTX-TKI (Axitinib implant).

	wet AMD	wet AMD	NPDR
Phase	I NCT04989699	I NCT03630315	I (HELIOS)
Geography	US	Australia	US
Status	Ongoing (positive interim results to date)	Completed (positive interim results, follow-up ongoing)	Initiated in December 2022^
No of Patients	21 (recruiting)	29	21 (Jan 2023)
Design	Randomized, Prospective, Multi-centre, Double-blind, Open-label, Parallel Assignment	Randomized, Multi-centre, Open-label, Dose-escalation, Sequential Assignment	Randomized, multicenter, double asked, parallel assignment
Inclusion criteria	• Previously treated subfoveal neovascularization (SFNV) secondary to nAMD with leakage involving the fovea • Previously treated with documented evidence of an initially favourable clinical response to anti-VEGF therapy • The macular appearance on OCT was free of excess intraretinal and/or subretinal fluid as judged by the investigator. • Must have received at least 3 anti-VEGF injections in the past year. • Have received the most recent anti-VEGF injection within the past 1 to 4 weeks prior to the screening visit. • BCVA ETDRS score between 24 & 83 letters approximately	• Eligible for standard therapy • Have active primary CNVM secondary to AMD - either newly diagnosed or previously treated with documented response to the anti-VEGF therapy in study eye • Post-menopausal women for at least 12 months prior to screening or surgically sterile • Male or female of childbearing potential willing to use two forms of adequate contraception	• Treatment naïve adults with NPDR secondary to diabetes mellitus type 1 or 2 • Moderately severe to severe NPDR (DRSS level 47 or 53, without DME)) in the study eye • BCVA ≥ 69 ETDRS letters (Snellen equivalent approximately 20/40 or better) in the study eye
Dose & Frequency	• One dose of OTX-TKI 600 µg. OTX-TKI is one dose so subsequent visits will be sham to maintain the mask • Aflibercept administered every 8 weeks	• Cohort 1: OTX-TKI, low dose (200 µg) • Cohort 2: OTX-TKI, Mid dose (400 µg) • Cohort 3a: OTX-TKI, High dose (600 µg) • Cohort 3b: Anti-VEGF + OTX-TKI (400 µg) • Cohort 4a: OTX-TKI, High dose (600 µg) single implant • Cohort 4: Anti-VEGF + OTX-TKI (600 µg) single implant	• 600 µg single implants (n = 14) • Sham comparator (n = 7)
Primary endpoint	Safety and Tolerability (12 months)	Incidence of treatment-emergent adverse events for each subject (9 months)	Safety, tolerability & biological activity (12 months)
Secondary endpoints	Change in BCVA & CST, Rescue Therapy, Absence of Fluid, Number of injections (an average of 1 year)	Determine the Maximum Tolerated Dose of the OTX-TKI injection (9 months)	NA
Baseline Mean (SD) BCVA Mean (SD) CSFT	• OTX-TKI: 73.7(14.4) letters • Aflibercept: 73.8(9.0) letters • OTX-TKI: 269(40.3) µm • Aflibercept: 240.6(29.6) µm	Interim data(n = 23) (41) • Cohort 1: 48(12.0) letters • Cohort 2: 62(8.5) letters • Cohort 3a: 46(6.4) letters • Cohort 3b: 47(11.8) letters • All patients: 51(4.7) letters • Cohort 1: 680(159) µm • Cohort 2: 450(29) µm • Cohort 3a: 521(68) µm • Cohort 3b: 435(58) µm • All patients: 526(49) µm	NA
Combined Results	OTX-TKI met its primary endpoint in both US & Australia Phase I trials with potential best-in-class durability observed. US study • Interim results demonstrated potential as a durable sustained release product AUS study • Interim 7-month results show potential as a durable sustained-release maintenance therapy for 6-12 months in subjects with controlled retinal fluid demonstrating biological activity in subjects with pre-existing fluid Proof of biological activity & maintenance therapy with SOC • Demonstrated a reduction in the retinal fluid in treatment naïve wet AMD subjects with active retinal fluid • Showed a sustained & stable maintenance of fluid and vision for 7 months in previously treated wet AMD subjects with controlled fluid Potential best-in-class durability & treatment burden reduction • Over 80% of subjects treated with OTX-TKI 600 µg were rescue-free at 6 months in both studies • A clinically meaningful reduction in the treatment burden of up to 93% Generally well-tolerated with a favourable safety profile • Over 850 subject visits from OTX-TKI clinical studies without any ocular SAEs • No drug-related ocular or systemic SAEs • No elevated intraocular pressure, retinal detachment, or implant dislocation into the anterior chamber events in the OTX-TKI cohort. AEs were mild & transient		NA
Separate results	Demonstrated stable & sustained BCVA and CST maintenance through 7 months in subjects with controlled fluid Mean (SD) change in BCVA from screening visit • -1.3(5.2) letters at 7 months OTX-TKI • -1.0(5.3) letters at 7 months aflibercept Mean (SD) change in CST from screening visit •  + 9.2(38.6) microns at 7 months OTX-TKI •  + 0.4(9.1) microns at 7 months Aflibercept • 80% of subjects were rescue-free for up to 6-months • 93% treatment burden reduction had shown at 7 months following a single OTX-TKI implant	OTX-TKI monotherapy demonstrated a clinically meaningful reduction in retinal fluid in treatment naïve subjects	NA

AE adverse event, anti-VEGF anti vascular endothelial growth factor, BCVA best corrected visual acuity, CNVM choroidal neovascular membrane, CST central subfield thickness, DR Diabetic retinopathy, DRSS Diabetic Retinopathy Severity Score, ETDRS Early treatment diabetic retinopathy study, nAMD neovascular age-related macular degeneration, NPDR Non-proliferative diabetic retinopathy, OCT optical coherence tomography, SAE serious adverse event; wet AMD wet age-related macular degeneration.