Superiority of a single axitinib implant over a single aflibercept 2 mg injection

“The SOL-1 trial is a prospective, multi-center, double-masked, randomized (1:1), parallel-group, two-arm superiority trial to assess the safety and efficacy of a single injection of AXPAXLI with a drug load of 450 µg of axitinib, or AXPAXLI 450 µg, compared with a single injection of aflibercept 2 mg, in subjects with wet AMD up to Week 52 and repeat-dosing thereafter.” (opens the source at this quote in a new tab)

Durability objective and intended dosing label

“We believe the design of the SOL-1 trial enhances the potential for a 6 - 12 month dosing label for AXPAXLI for the treatment of wet AMD and also provides insights into the long-term durability of AXPAXLI.” (opens the source at this quote in a new tab)

“Compares a single OTX-TKI (0.45 mg) dose to a single aflibercept (2 mg) dose” (opens the source at this quote in a new tab)
“Designed to show superiority on efficacy and durability” (opens the source at this quote in a new tab)

Registry dates

Milestone	Registry record
Study start (actual)	“2024-01-29”
Primary completion (estimated)	“2026-04-29”
Study completion (estimated)	“2027-09-27”

Countries and number of sites

“The SOL-1 trial involves more than 100 trial sites located in the United States and Argentina.” (opens the source at this quote in a new tab)

Registered site countries

Country listed in the registry
“United States”
“Argentina”
“Puerto Rico”

First subjects screened

“today announced that the first three subjects have been screened and received their first aflibercept injection in the Phase 3 SOL-1 clinical trial of AXPAXLI™ (axitinib intravitreal implant, also known as OTX-TKI) for the treatment of wet age-related macular degeneration (wet AMD).” (opens the source at this quote in a new tab)

Completion of randomization and Week 52 database lock

“In December 2024, we completed the randomization of 344 subjects with a diagnosis of wet AMD in the study eye at screening in the SOL-1 trial.” (opens the source at this quote in a new tab)
“As of the Week 52 database lock on February 5, 2026, AXPAXLI was generally well-tolerated in the SOL-1 trial.” (opens the source at this quote in a new tab)

Randomized, double-masked, parallel-group superiority design

“The SOL-1 trial is designed as a prospective, multi-center, double-masked, randomized (1:1), parallel-group, two-arm superiority trial that involves more than 100 trial sites located in the United States and Argentina.” (opens the source at this quote in a new tab)

Registered design details

Design element	Registry record
Allocation	“Randomized”
Interventional model	“Parallel Assignment”
Interventional model description	“1:1”
Masking	“Quadruple”
Collaborators	“Fortrea”
Collaborators	“Duke University”

Eight-week aflibercept loading segment before randomization

“The superiority trial has an eight-week loading segment prior to randomization.” (opens the source at this quote in a new tab)
“This is a population that was specifically selected to lose vision.” (opens the source at this quote in a new tab)

Stratification at randomization

“In addition, the subjects were stratified between the two treatment groups at randomization based on BCVA category (≤ 71 and >71 ETDRS letters) as of the initial screening visit.” (opens the source at this quote in a new tab)

Identical dosing schedules without sham injections

“Both study arms have the same dosing schedule” (opens the source at this quote in a new tab)
“No sham injections in either arm” (opens the source at this quote in a new tab)

Masking and follow-up through Week 104

“In accordance with the trial design, subjects will be followed for safety, and subjects and designated trial personnel will remain masked, through Week 104.” (opens the source at this quote in a new tab)

Special Protocol Assessment agreement and modifications

“We received an agreement letter regarding the overall trial design from the FDA under the SPA agreement on October 30, 2023.” (opens the source at this quote in a new tab)
“In December 2023, we submitted a first SPA agreement modification to the FDA to broaden the inclusion criteria for subjects in the SOL-1 trial and to reflect our intention to evaluate a single optimized dose of AXPAXLI 450 μg of a more soluble form of axitinib in the trial.” (opens the source at this quote in a new tab)
“We received an agreement letter regarding the first SPA agreement modification from the FDA on January 22, 2024.” (opens the source at this quote in a new tab)
“In January 2025, we submitted a subsequent SPA agreement modification to the FDA to add a repeat dose of AXPAXLI 450 µg at Week 52 and at Week 76, in each case, after all pre-defined efficacy endpoint assessments, to generate the required safety data for subjects re-dosed with AXPAXLI 450 μg through Week 104, to support long-term dosing.” (opens the source at this quote in a new tab)
“We received an agreement letter regarding the second SPA agreement modification from the FDA on February 24, 2025.” (opens the source at this quote in a new tab)

Independent rescue monitoring

“Independent rescue monitor team of retina specialists were designated to provide guidance” (opens the source at this quote in a new tab)

Registered inclusion criteria

“Treatment naïve for Neovascular Age-Related Macular Degeneration (nAMD) in either eye at screening.” (opens the source at this quote in a new tab)
“Are at least older than 50 years of age at Day 1.” (opens the source at this quote in a new tab)
“Have Best Corrected Visual Acuity (BCVA) of at least 84 Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (approximate 20/20 Snellen equivalent) at Day 1; OR have an increase of at least 10 ETDRS letters of Best Corrected Visual Acuity (BCVA) from Screening (Visit 1) BCVA” (opens the source at this quote in a new tab)

Registered exclusion criteria

“Monocular subjects or a Best Corrected Visual Acuity (BCVA) score of 20/200 in fellow eye at screening.” (opens the source at this quote in a new tab)
“Have evidence of a scar, fibrosis, or atrophy of > 50% of the total lesion in the study eye.” (opens the source at this quote in a new tab)

Enrollment and randomization criteria: congress presentation

Stage	Quoted criterion
Enrollment (screening)	“Treatment naïve for nAMD”
Enrollment (screening)	“BCVA ≥54 ETDRS letters (~20/80)”
Enrollment (screening)	“CSFT of ≤500 μm”
Randomization (Day 1)	“BCVA gain ≥10 ETDRS letters OR BCVA ≥84 ETDRS letters (~20/20)”
Randomization (Day 1)	“CSFT of ≤350 μm”

Enrollment and randomization criteria: quarterly report

“had a Best Corrected Visual Acuity, or BCVA, of at least 54 letters as measured by the Early Treatment of Diabetic Retinopathy Study, or ETDRS, letters chart (approximately 20/80 Snellen equivalent vision).” (opens the source at this quote in a new tab)
“Subjects reaching either a BCVA of greater than or equal to 84 ETDRS letters (approximately 20/20 Snellen equivalent vision) or experiencing an improvement of at least 10 ETDRS letters with a reduction in CSFT to no greater than 350 microns in the study eye after these injections were randomized in the trial on Day 1 (Baseline).” (opens the source at this quote in a new tab)

Enrollment and randomization criteria: topline results announcement

“During the loading segment, subjects who have 20/80 vision or better and a central subfield thickness (CSFT) of ≤500 μm receive two doses of aflibercept (2 mg) at Week -8 and Week -4. Subjects who achieve best corrected visual acuity (BCVA) of 20/20 at Day 1 (baseline) or gain at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at Day 1 along with a CSFT of ≤350 μm were then randomized to receive a single dose of AXPAXLI or a single dose of aflibercept (2 mg).” (opens the source at this quote in a new tab)

Broadened visual acuity criterion under the first SPA modification

“The SPA Agreement Modification enables the trial to include treatment-naïve wet AMD subjects with visual acuity of approximately 20/80 or better at the initial screening visit.” (opens the source at this quote in a new tab)

Registered interventions

Arm	Registry intervention description
Experimental	“Intravitreal Injection of OTX-TKI (axitinib implant)”
Control	“Injection of 2mg (0.05mL) of aflibercept”

Day 1 treatment and no aflibercept at baseline in the implant arm

“No aflibercept injection is given at baseline” (opens the source at this quote in a new tab)

Optimized 450 µg implant formulation

“The SPA Agreement Modification also allows the pivotal trial to move forward, evaluating AXPAXLI with a single optimized implant with a drug load of 450 µg of a more soluble form of axitinib. This optimized configuration is expected to provide for a slightly increased daily release of the drug and is designed to improve synchronization of axitinib drug depletion with hydrogel bioresorption.” (opens the source at this quote in a new tab)

Monthly visits and redosing at Weeks 52 and 76

“Throughout the trial, subjects are assessed monthly.” (opens the source at this quote in a new tab)
“At Weeks 52 and 76, all subjects that were randomized in the trial at Day 1, including subjects who previously received supplemental anti-VEGF treatment, are re-dosed with their respective initial treatment of a single injection of AXPAXLI 450 μg in the investigational arm or a single injection of aflibercept 2 mg in the control arm.” (opens the source at this quote in a new tab)

Rescue criteria: annual report

“Our pre-specified rescue criteria are a loss of 15 or more letters on the ETDRS chart compared to baseline due to wet AMD, or a new hemorrhage that is deemed to be likely to cause irreversible vision loss due to progression of wet AMD.” (opens the source at this quote in a new tab)

Rescue criteria: congress presentation

“Rescue Criteria: BCVA loss ≥15 ETDRS letters from baseline due to nAMD; or New macular hemorrhage that would likely lead to irreversible vision loss if left untreated in the opinion of the investigator after discussion with Medical Monitor” (opens the source at this quote in a new tab)

Rescue after the first rescue injection

“The protocol provides that after the first rescue injection, rescue therapy may be provided at investigator discretion per their clinical judgement.” (opens the source at this quote in a new tab)

Injector used for administration

“All subjects in two of our Phase 1 trials of AXPAXLI, as well as most of the subjects in the SOL-1 trial and a small subset of subjects in the SOL-R trial were dosed with AXPAXLI using our two-piece injector.” (opens the source at this quote in a new tab)
“As a future lifecycle initiative for AXPAXLI, we may continue development of a next-generation one-piece injector which was used to dose AXPAXLI to a subset of subjects in both the SOL-1 and SOL-R trials.” (opens the source at this quote in a new tab)

Registered outcome measures

Outcome type	Measure	Description	Time frame
Primary	“Best corrected visual acuity (BCVA)”	“Maintenance of visual acuity, defined as < 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters Best corrected visual acuity (BCVA) loss”	“Up to 36 Weeks”
Other	“Incidence and severity of treatment emergent adverse events (AEs)”	“Changes Safety Outcomes from Baseline”	“Up to 104 Weeks”

Primary endpoint definition and treatment-failure rule

“The primary endpoint is the proportion of subjects who maintain visual acuity, defined as a Best Corrected Visual Acuity, or BCVA, loss of fewer than 15 letters on the Early Treatment of Diabetic Retinopathy Study, or ETDRS, letters chart from baseline at Week 36.” (opens the source at this quote in a new tab)
“The first time a subject is observed to have lost 15 or more ETDRS letters in BCVA in the study eye due to wet AMD at any time up to Week 36 in the trial would be considered as having met the endpoint as a treatment failure.” (opens the source at this quote in a new tab)

Alignment with FDA draft guidance and the SPA agreement

“The SOL-1 primary endpoint was designed to support a potential superiority label in wet AMD based on the FDA’s 2023 draft guidance for wet AMD therapies and was agreed to by the FDA in the Company’s SPA agreement.” (opens the source at this quote in a new tab)

FDA-recommended superiority endpoints at 9 months or later

“Statistically significant smaller % of subjects with ≥15-letter decrease at 9 months or later” (opens the source at this quote in a new tab)
“Statistically significant greater % of subjects with ≥15-letter increase at 9 months or later” (opens the source at this quote in a new tab)
“Statistically significant difference between groups in mean BCVA of ≥15 letters at 9 months or later” (opens the source at this quote in a new tab)
“SOL-1 Primary Endpoint: Proportion of subjects who maintained visual acuity, defined as <15 ETDRS letters of BCVA loss from baseline at Week 36” (opens the source at this quote in a new tab)

Constraints of the SPA agreement

“With acceptance of SPA, study design, endpoints, and SAP cannot be changed” (opens the source at this quote in a new tab)

Key secondary and secondary endpoints in hierarchical order

Endpoint type and order	Quoted endpoint
Key secondary 1	“Proportion of subjects who maintained visual acuity** with one rescue injection or fewer at Week 52”
Key secondary 2	“Proportion of subjects who maintained visual acuity** at Week 52”
Key secondary 3	“Proportion of subjects who maintained visual acuity** with one rescue injection or fewer at Week 36”
Key secondary 4	“BCVA change from baseline at Week 36”
Key secondary 5	“BCVA change from baseline at Week 52”
Secondary 1	“CSFT changes from baseline at Weeks 36”
Secondary 2	“Proportion with no CSFT increase (≤50 microns) at Weeks 36”
Secondary 3	“Proportion CSFT ≤ 350 microns at Weeks 36 and 52”
Secondary 4	“Mean time to the first rescue injection”
Secondary 5	“Mean time to the second rescue injection”
Secondary 6	“Proportion of subjects who lose ≥ 10 letters at Weeks 36 and 52”

Pre-specified exploratory endpoints

“As a pre-specified exploratory endpoint, Ocular evaluated the proportion of patients who did not require rescue injections as specified by the protocol rescue criteria, which includes a BCVA loss of ≥15 ETDRS letters from baseline or new vision-threatening macular hemorrhage.” (opens the source at this quote in a new tab)
“As a pre-specified exploratory endpoint, Ocular evaluated the proportion of subjects maintaining Central Subfield Thickness (CSFT) within 30 μm from baseline.” (opens the source at this quote in a new tab)

Planned sample size

“The trial is intended to randomize approximately 300 evaluable treatment-naïve subjects with a diagnosis of wet AMD in the study eye.” (opens the source at this quote in a new tab)

Registered actual enrollment

Item	Registry record
Enrollment (actual)	“344”

Randomized participants and withdrawals before Day 1 treatment

“In December 2024, the trial completed randomization of 344 treatment-naïve subjects with a diagnosis of wet AMD in the study eye. Two randomized subjects withdrew from the trial prior to receiving Day 1 treatment.” (opens the source at this quote in a new tab)

“In December 2024, the SOL-1 trial completed randomization of 344 evaluable treatment-naïve subjects with a diagnosis of wet AMD in the study eye who have 20/80 vision or better and a central subfield thickness, or CSFT, of not more than 500 µm.” (opens the source at this quote in a new tab)

Participants analyzed by analysis

Analysis	Axitinib implant 0.45 mg	Aflibercept 2 mg
Randomized	“OTX-TKI 0.45 mg N = 172”	“Aflibercept 2 mg N = 172”
Full analysis set (efficacy)	“OTX-TKI 0.45 mg (n=170)”	“Aflibercept 2 mg (n=172)”
Safety tables through Week 52	“OTX-TKI 0.45 mg n = 170”	“Aflibercept 2 mg n = 172”
Screening BCVA quartile 1, post hoc	“OTX-TKI Q1 (n=41)”	“AFL Q1 (n=52)”
Screening BCVA quartile 2, post hoc	“OTX-TKI Q2 (n=39)”	“AFL Q2 (n=39)”
Screening BCVA quartile 3, post hoc	“OTX-TKI Q3 (n=46)”	“AFL Q3 (n=41)”
Screening BCVA quartile 4, post hoc	“OTX-TKI Q4 (n=44)”	“AFL Q4 (n=40)”
Rescue-free participants through Week 36, post hoc	“OTX-TKI 0.45 mg (n=127)”	“Aflibercept 2 mg (n=97)”
Participants with CSFT at Week 8, post hoc	“OTX-TKI 0.45 mg (n=165)”	“Aflibercept 2 mg (n=164)”

Participants exposed to the implant for the planned NDA safety database

“To provide safety information for a minimum of 300 subjects in the aggregate with at least one year of treatment with AXPAXLI in accordance with FDA guidance and to supplement the 170 subjects who received AXPAXLI in the SOL-1 trial, we plan to conduct an interim safety analysis of the SOL-R trial during the fourth quarter of 2026 assessing all subjects who have completed the Week 52 time point at the time of analysis.” (opens the source at this quote in a new tab)

Full analysis set and exclusion of misrandomized participants

“Two OTX-TKI subjects were misrandomized, did not receive study treatment and were not included in the full analysis set” (opens the source at this quote in a new tab)

Handling of treatment discontinuation and statistical model

“Predefined statistical rules were applied to adjust for treatment discontinuation or deviation as per the pre-specified statistical analysis plan.” (opens the source at this quote in a new tab)
“The risk difference is the difference in the probability of maintaining vision in the treatment arm compared to the control arm as per the pre-specified statistical model. The observed difference is the numerical difference of the observed event rate between the two arms.” (opens the source at this quote in a new tab)

Censoring of BCVA and CSFT after first rescue in descriptive analyses

“For subjects who received any rescue injections, their observed BCVA and CSFT values after the 1st rescue injection are set to missing. Baseline measurements are the last non-missing measurement prior to the study drug injection on Day 1.” (opens the source at this quote in a new tab)

Hierarchical testing of key secondary endpoints and sensitivity analyses

“Key secondary endpoints achieved in accordance with the prespecified hierarchy” (opens the source at this quote in a new tab)

“All six pre-specified sensitivity analyses for the SOL-1 primary endpoint at Week 36 were statistically significant, and the first three of five hierarchically controlled key secondary endpoints were also met with statistical significance.” (opens the source at this quote in a new tab)

Rescue-free subgroup definition

“Rescue-free subjects include those who did not require rescue injections as specified by the protocol” (opens the source at this quote in a new tab)

Analysis set for time to CSFT increase

“Subjects with CSFT at Week 8 in Full Analysis Set” (opens the source at this quote in a new tab)

Disposition through Week 52

Disposition item	Axitinib implant 0.45 mg	Aflibercept 2 mg
Randomized	“N=172”	“N=172”
Discontinued before Week 52	“Discontinued before Week 52 (n=11)”	“Discontinued before Week 52 (n=5)”
Adverse event	“Adverse event (n=1)”	“Adverse event (n=2)”
Withdrew consent	“Subject withdrew consent* (n= 6)”	“Subject withdrew consent* (n=1)”
Death	“Death (n=1)”	“Death (n=1)”
Lost to follow-up	“Lost to follow-up (n=1)”	“Lost to follow-up (n=1)”
Completed through Week 52	“n=161 (94%)”	“n=167 (97%)”

Misrandomized participants

“Mis-randomized (n=2)†” (opens the source at this quote in a new tab)
“Subjects did not receive study treatment and were not included in the full analysis set” (opens the source at this quote in a new tab)

Reasons for consent withdrawal

“Reasons included: personal reason, no reason, travel, offered another treatment at a different practice; only Day 1 completed, subject refused week 52 assessment” (opens the source at this quote in a new tab)

Retention and protocol-defined rescues

“Retention in the SOL-1 trial continues to be outstanding, with greater than 95% of randomized subjects remaining on trial to date, and rescues reviewed under masking show greater than 95% of rescue events to date have met pre-established protocol defined criteria.” (opens the source at this quote in a new tab)

Demographics

Characteristic	Axitinib implant 0.45 mg (N = 172)	Aflibercept 2 mg (N = 172)
Age, years, mean (SD)	“75.7 (8.3)”	“76.3 (7.4)”
Female, n (%)	“103 (59.9)”	“108 (62.8)”
Hispanic or Latino, n (%)	“33 (19.2)”	“47 (27.3)”
Not Hispanic or Latino, n (%)	“139 (80.8)”	“125 (72.7)”
White, n (%)	“168 (97.7)”	“170 (98.8)”

Study eye visual acuity and CSFT at screening and baseline

Characteristic	Axitinib implant 0.45 mg (N = 172)	Aflibercept 2 mg (N = 172)
Screening (Week -8) BCVA, ETDRS letters, mean (SD)	“70.9 (11.3)”	“69.5 (10.8)”
Screening (Week -8) CSFT, μm, mean (SD)	“303.6 (72.5)”	“302.7 (78.3)”
Baseline (randomization) BCVA, ETDRS letters, mean (SD)	“80.8 (7.6)”	“79.2 (7.9)”
Baseline (randomization) CSFT, μm, mean (SD)	“219.3 (37.1)”	“226.8 (42.1)”
Change from screening to baseline, ≥10 ETDRS letter gain, n (%)	“107 (62.9)”	“114 (67.1)”
Change from screening to baseline, ≥84 ETDRS letters (~20/20), n (%)	“63 (37.1)”	“56 (32.9)”

Study eye ocular characteristics at baseline

Characteristic	Axitinib implant 0.45 mg (N = 172)	Aflibercept 2 mg (N = 172)
BCVA >71 letters (~ 20/40), stratification category, n (%)	“145 (85.3)”	“136 (79.1)”
Presence of any fluid (IRF and/or SRF), n (%)	“63 (36.6)”	“72 (41.9)”
Presence of IRF, n (%)	“34 (19.8)”	“36 (20.9)”
Presence of SRF, n (%)	“33 (19.2)”	“48 (27.9)”
Presence of hemorrhage, n (%)	“69 (40.6)”	“60 (34.9)”
Phakic, n (%)	“74 (43.5)”	“78 (45.3)”

Baseline macular atrophy

Measure	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)
Any macular atrophy at baseline	“8.2%”	“7.6%”
Macular atrophy in the central 1 mm at baseline	“1.2%”	“1.2%”

Comparison of baseline visual acuity with other nAMD registration trials

“SOL-1 mean BCVA: 81 letters (~20/25) mean CSFT: 219 μM” (opens the source at this quote in a new tab)
“nAMD Trials mean BCVA: 52 to 62 letters (~20/100 to 20/60)” (opens the source at this quote in a new tab)

Summary: Week 36 and Week 52 efficacy

The primary endpoint was met: at Week 36, 74.1% of participants in the axitinib implant arm (n=170) and 55.8% in the aflibercept 2 mg arm (n=172) maintained vision (model-based risk difference 17.5%, 95% CI 7.7 to 27.4; p=0.0006; observed difference 18.3%). At Week 52, the corresponding proportions were 65.9% and 44.2% (risk difference 21.1%; p<0.0001). The first three of five hierarchically tested key secondary endpoints were met; the fourth and fifth, mean BCVA change from baseline at Weeks 36 and 52, were not reported as met, and no mean BCVA change from baseline values were identified for the full analysis set. Rescue-free rates were 80.6%, 74.7%, and 68.8% at Weeks 24, 36, and 52 with the implant versus 72.1%, 56.4%, and 47.7% with aflibercept. The company describes the rescue-free and CSFT within 30 μm analyses as pre-specified exploratory endpoints in its topline announcement, while congress slides label the same analyses post hoc. Most additional analyses (CSFT time-to-event, screening BCVA quartiles, rescue-free subgroup, treatment burden) are post hoc with descriptive or nominal p-values.

Primary endpoint and Week 52 key secondary endpoint: maintenance of vision

Measure	Week 36 (primary endpoint)	Week 52 (key secondary endpoint)
Axitinib implant 0.45 mg (n = 170), proportion maintaining vision	“74.1%”	“65.9%”
Aflibercept 2 mg (n = 172), proportion maintaining vision	“55.8%”	“44.2%”
Risk difference vs. aflibercept 2 mg	“17.5%”	“21.1%”
95% CI	“(7.7, 27.4)”	“(10.8, 31.4)”
P value	“P = 0.0006”	“P < 0.0001”
Observed difference vs. aflibercept 2 mg	“aflibercept 2 mg 18.3%”	“aflibercept 2 mg 21.7%”

Primary endpoint and Week 52 key secondary endpoint: annual report narrative

“The proportion of subjects who maintained visual acuity, defined as a loss of fewer than 15 ETDRS letters from baseline, at Week 36 was 74.1% in the AXPAXLI arm compared to 55.8% in the aflibercept 2 mg arm, with a risk difference of 17.5% and a p-value of 0.0006 per the pre-specified statistical model, and with an observed difference of 18.3%.” (opens the source at this quote in a new tab)
“The proportion of subjects who maintained vision at Week 52 was 65.9% in the AXPAXLI arm compared to 44.2% in the aflibercept 2 mg arm, with a risk difference of 21.1%, and a p-value of <0.0001 per the pre-specified statistical model compared to aflibercept 2 mg subjects, and with an observed difference of 21.7%.” (opens the source at this quote in a new tab)

Sensitivity analyses of the primary endpoint

“Multiple sensitivity analyses for the primary endpoint were also statistically significant and confirm that the data are robust.” (opens the source at this quote in a new tab)

Key secondary endpoints 1 to 3

Key secondary endpoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)	Risk difference vs. aflibercept	P value
Maintained vision with ≤1 rescue injection at Week 52	“72.4%”	“54.1%”	“17.7% (95% CI, 7.7, 27.8)”	“P = 0.0007”
Maintained vision at Week 52	“65.9%”	“44.2%”	“21.1% (95% CI, 10.8, 31.4)”	“P < 0.0001”
Maintained vision with ≤1 rescue injection at Week 36	“81.2%”	“66.9%”	“13.8% (95% CI, 4.6, 22.9)”	“P = 0.0036”

Key secondary endpoints 4 and 5: BCVA change from baseline

“Strong overall efficacy profile with unmatched durability: Achieved statistical significance in the first three of five key secondary endpoints tested in hierarchical order. In addition, six other pre-specified secondary endpoints measuring clinically significant functional and anatomic outcomes were met with statistical significance.” (opens the source at this quote in a new tab)

Secondary endpoint: proportion with CSFT of 350 μm or less

Timepoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)	Risk difference vs. aflibercept	Nominal p-value
Week 36	“68.8%”	“52.9%”	“15.0% (95% CI, 4.9, 25.1)”	“P = 0.0041*”
Week 52	“64.7%”	“43.6%”	“20.4% (95% CI, 10.1, 30.7)”	“P = 0.0001*”

Secondary endpoint: proportion losing 10 or more ETDRS letters

Timepoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)	Risk difference vs. aflibercept	Nominal p-value
Week 36	“34.1%”	“50.6%”	“-15.9% (95% CI-26.3, -5.6)”	“P = 0.0029*”
Week 52	“47.6%”	“59.3%”	“-10.9% (-21.4, -0.5)”	“P = 0.0423*”

Rescue-free rates: congress presentation, labeled post hoc

Timepoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)	Descriptive p-value
Week 24	“80.6%”	“72.1%”	“P = 0.0856*”
Week 36	“74.7%”	“56.4%”	“P = 0.0006*”
Week 52	“68.8%”	“47.7%”	“P = 0.0001*”

“Post-hoc analysis; Full analysis set; *Descriptive p-values” (opens the source at this quote in a new tab)

Rescue-free rates: quarterly report, with observed differences

“The rescue-free rates in the AXPAXLI arm were 80.6%, 74.7%, and 68.8% at Weeks 24, 36, and 52, respectively, compared to 72.1%, 56.4%, and 47.7% in the aflibercept 2 mg arm at the same time periods. The observed differences were 8.5%, 18.3%, and 21.1% in favor of the AXPAXLI arm at Weeks 24, 36, and 52, respectively.” (opens the source at this quote in a new tab)

Rescue-free rates: rounded values in a later announcement

“Of note, 81% of the AXPAXLI subjects were rescue-free at Week 24.” (opens the source at this quote in a new tab)

Secondary endpoint: time to first rescue treatment

“P = 0.0005*” (opens the source at this quote in a new tab)
“Rescue-free subjects include those who did not require rescue injections as specified by the protocol” (opens the source at this quote in a new tab)

“AXPAXLI Week 52 rescue rate reflects ~6-month advantage over aflibercept” (opens the source at this quote in a new tab)

Rescue-free rate at Week 24 applying SOL-R rescue criteria

“In a prespecified exploratory analysis applying the SOL-R protocol rescue criteria to the SOL-1 results, AXPAXLI demonstrated a 77.1% rescue-free rate at Week 24.” (opens the source at this quote in a new tab)
“The protocol rescue criteria in SOL-R of >5 ETDRS letter loss in BCVA plus a ≥75 μm increase in CSFT are designed to track more closely with real-world clinical practice as compared to the rescue criteria used in SOL-1.” (opens the source at this quote in a new tab)

Rescue-free rate at Week 52 applying SOL-R rescue criteria and estimated injection burden, post hoc

“The proportion of SOL-1 patients who would have remained rescue-free under the SOL-R rescue criteria of >5 ETDRS letter loss and ≥75 µm CSFT increase from baseline was 66.5% at Week 52. Applying the observed mean rescue treatment rates in SOL-1 to the estimated 33.5% of subjects requiring rescue under the SOL-R criteria corresponded to an average of 0.95 aflibercept (2 mg) rescues per subject for all subjects in the AXPAXLI arm through Week 52 after a single AXPAXLI injection at baseline. The total estimated mean injection burden with AXPAXLI represents a 72% reduction counting from the first screening visit at Week -8 excluding loading doses and a 56% reduction when loading doses are included, as compared to a projected on-label dosing regimen of aflibercept (2 mg) with no rescues.” (opens the source at this quote in a new tab)

Mean number of expected injections per subject, Week -8 to Week 52	Axitinib implant	Aflibercept 2 mg (projected)	Injection burden reduction
Excluding loading doses	“1.95”	“7.00”	“72”
Including loading doses	“3.95”	“9.00”	“56”

CSFT maintained within 30 μm of baseline: topline announcement, labeled pre-specified exploratory

“Week 36: 55.9% of subjects treated with AXPAXLI maintained CSFT within 30 μm from baseline versus 37.8% of subjects in the aflibercept (2 mg) arm, representing a risk difference of 17.1% in favor of AXPAXLI (nominal p=0.0013).” (opens the source at this quote in a new tab)
“Week 52: 44.1% of subjects treated with AXPAXLI maintained CSFT within 30 μm from baseline versus 34.9% of subjects in the aflibercept (2 mg) arm, representing a risk difference of 8.4% in favor of AXPAXLI (nominal p=0.1094).” (opens the source at this quote in a new tab)

CSFT increase of 30 μm or less from baseline: congress presentation, labeled post hoc

Timepoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)	Risk difference vs. aflibercept	Descriptive p-value
Week 24	“51.8%”	“40.1%”	“11.0% (95% CI, 0.6, 21.5)”	“P = 0.0403*”
Week 36	“55.9%”	“37.8%”	“17.1% (95% CI, 6.8, 27.4)”	“P = 0.0013*”
Week 52	“44.1%”	“34.9%”	“8.4% (95% CI, -1.8, 18.7)”	“P = 0.1094*”

“Full analysis set. Post hoc analysis; *Descriptive p-value” (opens the source at this quote in a new tab)

Time to CSFT increase from Week 8, post hoc: announcement and congress presentation

“The median time to ≥30 uM Central Subfield Thickness (CSFT) increase from Week 8 was 39 weeks in the AXPAXLI group and 16 weeks in the aflibercept (2 mg) group, a 23-week difference. An estimated hazard ratio of 0.7 indicates that, at any time from Week 8 to Week 52, subjects in the treatment group experienced a 30% lower risk of the event (descriptive p=0.0028) compared with the control group.” (opens the source at this quote in a new tab)
“The median time to ≥75 uM CSFT increase from Week 8 was 46 weeks in the AXPAXLI group and 24 weeks in the aflibercept (2 mg) group, a 22-week difference. An estimated hazard ratio of 0.5 indicates that, at any time from Week 8 to Week 52, subjects in the treatment group experienced a 50% lower risk of the event (descriptive p<0.0001) compared with the control group.” (opens the source at this quote in a new tab)

Time to CSFT increase of 30 μm or more from Week 8: investor presentation reporting a different p-value

“~6-month difference in time to a 30 μm CSFT gain in favor of AXPAXLI suggests exceptional disease control” (opens the source at this quote in a new tab)
“P < 0.0001*” (opens the source at this quote in a new tab)

Mean BCVA and CSFT change from screening through Week 36, post hoc

Measure	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)
BCVA change from screening at Week 24, ETDRS letters	“+6.5”	“+4.9”
BCVA change from screening at Week 36, ETDRS letters	“+6.6”	“+5.4”
CSFT change from screening at Week 24, μm	“-43.0”	“-32.6”
CSFT change from screening at Week 36, μm	“-59.0”	“-31.7”

Mean BCVA and CSFT at Week 36, post hoc

Measure	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)
Mean BCVA at baseline, ETDRS letters	“80.8”	“79.2”
Mean BCVA at Week 36, ETDRS letters	“78.0”	“76.6”
Mean CSFT at baseline, μm	“219.3”	“226.8”
Mean CSFT at Week 36, μm	“238.3”	“258.0”

Mean change in total intraretinal and subretinal fluid volume from baseline: values as labeled in each presentation

Timepoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)
Week 24	“+31.1”	“+49.5”
Week 36	“+30.6”	“+54.0”

Timepoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)
Week 24	“32 nL”	“54 nL”
Week 36	“31 nL”	“59 nL”

Timepoint	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)
Week 36	“31 nL”	“59 nL”

Maintenance of vision at Week 36 by baseline fluid status

Subgroup	Axitinib implant	Aflibercept 2 mg	Risk difference (95% CI)
Overall	“74.1%”	“55.8%”	“17.5 (7.7, 27.4)”
IRF/SRF absent	“80.4%”	“56.0%”	“23.5 (11.1, 35.9)”
IRF/SRF present	“63.5%”	“55.6%”	“9.1 (-7.1, 25.3)”
IRF absent	“77.2%”	“57.4%”	“18.3 (7.4, 29.2)”
IRF present	“61.8%”	“50.0%”	“12.4 (-11.1, 36.0)”
SRF absent	“76.6%”	“56.5%”	“19.4 (8.2, 30.7)”
SRF present	“63.6%”	“54.2%”	“9.8 (-11.1, 30.8)”

BCVA by screening BCVA quartile, post hoc

“For example, AXPAXLI subjects in the lowest vision quartile group at screening had the greatest visual gains with +11.8 ETDRS letters compared to +8.5 letters in the aflibercept (2 mg) arm at Week 52. The mean vision at screening in this arm is similar to baseline BCVA in prior wet AMD studies. In comparison, subjects in the best vision quartile at screening had essentially no change in vision at Week 52 (-0.5 vs +1.1 letters; AXPAXLI vs aflibercept) as they started with almost 20/20 vision.” (opens the source at this quote in a new tab)

Quartile	Mean screening BCVA, axitinib implant	Mean screening BCVA, aflibercept 2 mg
Quartile 1	“55.5”	“56.8”
Quartile 2	“67.2”	“66.3”
Quartile 3	“75.7”	“75.7”
Quartile 4	“83.6”	“82.7”

BCVA change in rescue-free participants, post hoc

“Observed difference for change in BCVA from baseline at Week 24 in the rescue-free subjects was -1.9 ETDRS letters in the AXPAXLI arm (+7.5 letters from screening) vs -2.6 letters in the aflibercept arm (+6.0 letters from screening).” (opens the source at this quote in a new tab)
“At Week 36, 75% of AXPAXLI subjects remained rescue-free and lost <1 additional letter from Week 24 (+6.6 letters from screening).” (opens the source at this quote in a new tab)

Observed BCVA change from baseline in rescue-free participants, ETDRS letters	Axitinib implant (n=127) and aflibercept 2 mg (n=97)
Week 24	“24w -1.9 -2.6”
Week 36	“36w -2.8 -2.9”

Persistence of vision maintenance from Month 9 to Month 12, post hoc

“Of subjects that maintained vision at Month 9, ~90% maintained vision at Month 12” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Summary: safety through Week 52

Through Week 52, ocular adverse events in the study eye occurred in 90 of 170 participants (52.9%) receiving the axitinib implant and 58 of 172 (33.7%) receiving aflibercept 2 mg; treatment-related ocular adverse events occurred in 15 (8.8%) and 1 (0.6%). One ocular serious adverse event (0.6%) occurred in the implant arm (severe vision loss due to posterior subcapsular cataract) and none were treatment related. Vitreous floaters were reported in 21 participants (12.4%) with the implant and 2 (1.2%) with aflibercept. Intraocular inflammation was reported as 9 events in 7 participants (4.1%) in the implant arm, all mild or moderate and resolved. No endophthalmitis, occlusive or non-occlusive retinal vasculitis, retinal detachment, or implant migration to the anterior chamber was reported in the implant arm. No intraocular pressure data and no Year 2 (post-redosing) safety data were identified.

Overview of adverse events through Week 52

Participants with AEs through Week 52, n (%)	Axitinib implant 0.45 mg (n = 170)	Aflibercept 2 mg (n = 172)
Non-ocular: ≥1 AE	“84 (49.4)”	“73 (42.4)”
Non-ocular: ≥1 SAE	“19 (11.2)”	“21 (12.2)”
Non-ocular: ≥1 study procedure-related AE	“1 (0.6)”	“0”
AE leading to study discontinuation	“3 (1.8)”	“3 (1.7)”
AE leading to death	“2 (1.2)”	“1 (0.6)”
Ocular, study eye: ≥1 AE	“90 (52.9)”	“58 (33.7)”
Ocular, study eye: ≥1 SAE	“1 (0.6)”	“0”
Ocular, study eye: ≥1 treatment-related AE	“15 (8.8)”	“1 (0.6)”
Ocular, study eye: ≥1 study procedure-related AE	“15 (8.8)”	“7 (4.1)”
Ocular AE leading to study discontinuation	“0”	“0”

Deaths and the ocular serious adverse event

“Stroke (day 103); worsening of metastatic melanoma (day 319); lung cancer metastatic (day 503)” (opens the source at this quote in a new tab)
“Severe vision loss due to 3+ PSC cataract, 78 ETDRS letters at baseline, recovered to 70 ETDRS letters after cataract surgery” (opens the source at this quote in a new tab)

Ocular adverse events in the study eye in more than 2% of participants

Adverse event, n (%)	Axitinib implant 0.45 mg (n = 170)	Aflibercept 2 mg (n = 172)
Vitreous floaters	“21 (12.4)”	“2 (1.2)”
Cataract	“12 (7.1)”	“5 (2.9)”
Conjunctival hemorrhage	“11 (6.5)”	“5 (2.9)”
Retinal hemorrhage	“10 (5.9)”	“17 (9.9)”
Dry eye	“7 (4.1)”	“2 (1.2)”
Vitreous detachment	“7 (4.1)”	“3 (1.7)”
Punctate keratitis	“6 (3.5)”	“0”
Vitreous opacities	“6 (3.5)”	“0”
Eye pain	“5 (2.9)”	“1 (0.6)”
Anterior chamber opacity	“4 (2.4)”	“0”
Posterior capsule opacification	“4 (2.4)”	“6 (3.5)”

Endophthalmitis, retinal vasculitis, retinal detachment, and implant migration

“As of the Week 52 database lock on February 5, 2026, AXPAXLI was generally well-tolerated in SOL-1 with no observed treatment-related ocular or systemic serious adverse events (SAEs). There were no events of endophthalmitis, occlusive or non-occlusive retinal vasculitis, retinal detachment, or implant migration to the anterior chamber observed in the AXPAXLI arm.” (opens the source at this quote in a new tab)

“There were no cases of endophthalmitis, occlusive or non-occlusive retinal vasculitis, confirmed by wide-field fluorescein angiography in uveitis cases (Reading Center graded)” (opens the source at this quote in a new tab)

Intraocular inflammation

“Nine events observed in 7 subjects in the OTX-TKI arm” (opens the source at this quote in a new tab)
“8 events treated with topical corticosteroids and resolved” (opens the source at this quote in a new tab)
“1 event (vitreous cells), mild in severity, resolved without treatment” (opens the source at this quote in a new tab)

Participant	MedDRA term	Eye	Severity	Medication
1	“Iritis”	“Study eye”	“Mild”	“Topical corticosteroids”
1	“Iritis”	“Study eye”	“Moderate”	“Topical corticosteroids”
2	“Iridocyclitis”	“Study eye”	“Mild”	“Topical corticosteroids”
3	“AC inflammation”	“Study eye”	“Moderate”	“Topical corticosteroids”
4	“Vitreal cells”	“Study eye”	“Mild”	“None”
5	“Iritis”	“Study eye”	“Mild”	“Topical corticosteroids”
6	“Eye inflammation”	“Study eye”	“Moderate”	“Topical corticosteroids”
7	“Iritis”	“Study eye”	“Mild”	“Topical corticosteroids”
7	“Uveitis”	“Study Eye”	“Moderate”	“Topical corticosteroids”
7	“Uveitis”	“Non-study eye”	“Mild”	“None”

Vitreous floaters: onset and effect on vision

Measure	Axitinib implant 0.45 mg (n = 23 events)	Aflibercept 2 mg (n = 2)
Time to onset, days, mean (SD)	“187.9 (64.0)”	“164.5 (164.8)”
Time to onset, days, median	“207.0”	“164.5”
BCVA change from prior visit before onset, ETDRS letters, mean (SD)	“-0.4 (5.0)”	“-5.5 (6.4)”

“23 events in the study eye, 21 subjects; No case observed to be associated with cataract formation” (opens the source at this quote in a new tab)
“OTK-TKI: Mean change from baseline (SD) in BCVA, -3.3 (8.2) ETDRS letters; median change from baseline, -1.0 ETDRS letters” (opens the source at this quote in a new tab)

“In all AXPAXLI subjects who had a vitreous floater AE, drug particles are no longer visible (mean time of 20 weeks)” (opens the source at this quote in a new tab)

Incidence of macular atrophy at Week 52

Measure	Axitinib implant 0.45 mg (n=170)	Aflibercept 2 mg (n=172)
Any macular atrophy at Week 52	“9.4%”	“10.3%”
Any macular atrophy, percent change from baseline	“OTX-TKI 0.45mg: 1.2%”	“Aflibercept 2 mg: 2.7%”
Macular atrophy in the central 1 mm at Week 52	“1.9%”	“1.8%”
Macular atrophy in the central 1 mm, percent change from baseline	“OTX-TKI 0.45mg: 0.7%”	“Aflibercept 2 mg: 0.6%”

Intraocular pressure

No evidence found.

Year 2 safety after redosing

“Masked safety data being monitored and DSMC recommends trial continuation” (opens the source at this quote in a new tab)

“At the standard 120-day safety update following the submission of our NDA, we plan to submit Year 2 safety data from the SOL-1 trial to the FDA to support the potential inclusion of repeat dosing on a label for AXPAXLI, if approved.” (opens the source at this quote in a new tab)

Summary

SOL-1 compared a single axitinib implant with a single aflibercept 2 mg injection rather than with aflibercept at its labeled every-8-week maintenance schedule, so the superiority result reflects durability after one dose of each agent, not comparative effectiveness against labeled anti-VEGF regimens; the treatment burden reduction versus on-label aflibercept is a post hoc projection that the company describes as illustrative. Enrollment was limited to treatment-naive eyes that responded to two aflibercept loading doses, and mean baseline BCVA was 80.8 and 79.2 ETDRS letters (approximately 20/25), compared with 52 to 62 letters in other nAMD registration trials; results may not apply to eyes with poorer vision, incomplete loading response, or prior treatment. Race was 97.7% and 98.8% White in the two arms. The primary endpoint is a responder definition (loss of fewer than 15 letters) under which aflibercept-treated participants were eligible for rescue; key secondary endpoints for mean BCVA change from baseline at Weeks 36 and 52 were not among the endpoints reported as met, and mean BCVA change values from baseline for the full analysis set were not identified. Several analyses highlighted by the company (rescue-free rates, CSFT within 30 μm, time to CSFT increase, quartile and rescue-free subgroups) are post hoc or exploratory with nominal p-values, and sources disagree on whether the rescue-free and CSFT analyses were pre-specified, on the p-value for time to a 30 μm CSFT increase (0.0028 versus less than 0.0001), and on the aflibercept retinal fluid volume change at Week 36 (54.0 versus 59 nL). All results available as of September 2026 are company press releases, SEC filings, and company-hosted congress slides; no peer-reviewed publication or registry results were identified, and the registry record was last updated in April 2025. Safety data cover 170 implant-treated participants through Week 52 after a single dose; data after redosing at Weeks 52 and 76, intraocular pressure data, and long-term safety are not yet reported, and vitreous floaters (12.4%) and intraocular inflammation (7 participants) were more frequent with the implant.

Registered study summary

“Study to Evaluate the Efficacy and Safety of Intravitreal OTX-TKI (Axitinib Implant) in Subjects with Neovascular Age- Related Macular Degeneration” (opens the source at this quote in a new tab)

Company-stated objective: non-inferiority of dosing every 24 weeks

“We are also conducting the SOL-R trial, a repeat-dosing Phase 3 clinical trial to evaluate the non-inferiority of AXPAXLI 450 μg dosed every 24 weeks for the treatment of wet AMD compared to aflibercept 2 mg dosed on-label every eight weeks.” (opens the source at this quote in a new tab)

Original role as the second registrational trial

“In a Type C written response, the FDA agreed that the SOL-R repeat dosing wet AMD study is appropriate as an adequate and well-controlled study in support of a potential New Drug Application (NDA) and product label. The FDA also noted that the use of one superiority study and one non-inferiority study is generally acceptable as the basis of an eventual NDA in wet AMD.” (opens the source at this quote in a new tab)

Revised role after the May 2026 FDA Type C meeting

“To provide safety information for a minimum of 300 subjects in the aggregate with at least one year of treatment with AXPAXLI in accordance with FDA guidance and to supplement the 170 subjects who received AXPAXLI in the SOL-1 trial, we plan to conduct an interim safety analysis of the SOL-R trial during the fourth quarter of 2026 assessing all subjects who have completed the Week 52 time point at the time of analysis. SOL-R efficacy data is not part of our planned NDA submission.” (opens the source at this quote in a new tab)

“Because SOL-R efficacy is no longer part of the planned NDA submission or review, Ocular intends to leverage the trial to best serve its long-term strategic objectives for AXPAXLI.” (opens the source at this quote in a new tab)

Summary: registry sites compared with company-reported countries

The ClinicalTrials.gov record (last updated 2025-06-17) lists 97 locations: 84 in the United States, 10 in Argentina, 2 in Australia, and 1 in Puerto Rico. It lists no sites in India, whereas company filings and releases from 2025 and 2026 describe sites in the United States, Argentina, India, and Australia, and a November 2025 release describes approximately 100 sites. The registry study start date (2024-11-27) is later than the company-reported initiation (June 2024) and first enrollment (July 2024); the registry start date coincides with the month in which direct enrollment opened (November 2024), according to a June 2025 presentation.

Registry dates

Milestone	Registry record
Study start (actual)	“2024-11-27”
Primary completion (estimated)	“2027-01-08”
Study completion (estimated)	“2027-01-08”
Last update posted	“2025-06-17”

Registry location count

“This study has 97 locations” (opens the source at this quote in a new tab)

Company-reported initiation and first enrollment

“In June 2024, we initiated the SOL-R trial, a repeat-dosing registrational Phase 3 clinical trial for the treatment of wet AMD.” (opens the source at this quote in a new tab)
“The first subject was enrolled in the SOL-R trial in July 2024.” (opens the source at this quote in a new tab)

Enrollment periods

“Initially enrolled SOL-1 randomization failures” (opens the source at this quote in a new tab)
“Opened direct enrollment in Nov 2024” (opens the source at this quote in a new tab)
“Closed enrollment end of May 2025 with loading and randomization ongoing” (opens the source at this quote in a new tab)

Company-reported countries and number of sites

“The SOL-R trial includes sites located in the U.S., Argentina, India, and Australia.” (opens the source at this quote in a new tab)

“Subjects for SOL-R are enrolled across approximately 100 sites in the U.S., Argentina, India, and Australia.” (opens the source at this quote in a new tab)

Earlier description of site regions: January 2025

“311 subjects enrolled across various stages of loading and randomization in the U.S. and South America as of January 10, 2024.” (opens the source at this quote in a new tab)

Registered design

“A Phase 3, Multicenter, Double-Masked, Randomized, Parallel Group Study to Evaluate the Efficacy and Safety of Intravitreal OTX-TKI (Axitinib Implant) in Subjects With Neovascular Age- Related Macular Degeneration” (opens the source at this quote in a new tab)

Three-arm randomized design with a 2:2:1 ratio

“The SOL-R trial is designed as a multi-center, double-masked, randomized (2:2:1), three-arm trial requiring subjects that were either treatment naïve or have been diagnosed with wet AMD in the study eye within about four months prior to screening.” (opens the source at this quote in a new tab)

Six-month screening and loading lead-in before randomization

“Over the six month screening and lead-in period prior to Baseline (Day 1) randomization, enrolled subjects were given three screening doses of any anti-VEGF therapy, excluding brolucizumab-dbll, and two monthly loading doses of aflibercept 2 mg prior to Day 1, and monitored to exclude subjects demonstrating early persistent fluid or significant retinal fluid fluctuations.” (opens the source at this quote in a new tab)

Aflibercept 8 mg arm for masking instead of sham injections

“A third arm evaluating 8 mg aflibercept dosed Q6M is incorporated in the SOL-R study to ensure adequate masking, following the FDA’s recommendation that sham injections do not provide complete masking and therefore may elicit potential bias.” (opens the source at this quote in a new tab)

Rescue criteria: loss of more than 5 letters combined with CSFT increase

“The clinical trial protocol requires that, during the trial, subjects in any arm meeting pre-specified rescue criteria will receive a supplemental dose of aflibercept 2 mg. The pre-specified rescue criteria include a loss of more than 5 ETDRS letters in BCVA from best recorded prior visit (baseline or later) due to wet AMD, combined with an increase of 75 microns or more in CSFT from prior lowest measurement (baseline or later) due to wet AMD.” (opens the source at this quote in a new tab)

“The pre-specified rescue criteria include a >5-letter loss in visual acuity plus a ≥75 μm increase in CSFT.” (opens the source at this quote in a new tab)

Rescue criteria: May 2025 description with a 10-letter threshold

“The pre-specified rescue criteria include loss of ≥ 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters of BCVA from baseline or a combination of worsening anatomical measures and BCVA loss.” (opens the source at this quote in a new tab)

Redosing schedule: 2024 description with a single redose at Week 24

“In the first arm, subjects are randomized to receive a single dose of AXPAXLI at Day 1 and are re-dosed at Week 24. In the second arm, subjects receive aflibercept (2 mg) on-label every 8 weeks. In a third arm, subjects receive a single dose of aflibercept (8 mg) at Day 1 and are re-dosed at Week 24, aligned to the AXPAXLI treatment arm for adequate masking.” (opens the source at this quote in a new tab)

Redosing schedule: current description with redosing at Weeks 24, 48, and 72

“Subjects in the first arm of the SOL-R trial received a single dose of AXPAXLI 450 μg at Day 1 and are re-dosed with AXPAXLI 450 μg at Weeks 24, 48, and 72.” (opens the source at this quote in a new tab)

Protocol amendment in 2026: masking extended to Week 96

“We have no plans to enroll additional subjects in SOL-R and are amending the trial protocol to extend sponsor masking through Week 96 to evaluate the new secondary endpoints described above.” (opens the source at this quote in a new tab)

Interim safety analysis and alpha penalty

“All data other than safety data for the interim analysis population will remain masked following the interim analysis, and SOL-R will incur a 0.0001 alpha penalty in connection with its primary statistical analysis as a result of conducting the interim analysis.” (opens the source at this quote in a new tab)

FDA written responses on registrational adequacy

“In a written Type C response received in August 2024, and a subsequent written response received in December 2024, the FDA agreed that the SOL-R repeat dosing wet AMD trial, with a primary endpoint at Week 56, should be appropriate as an adequate and well-controlled trial in support of a potential NDA and product label for AXPAXLI for the treatment of wet AMD.” (opens the source at this quote in a new tab)

Registered inclusion criteria

“Treatment naïve juxtafoveal and/or SFNV secondary to Neovascular Age- Related Macular Degeneration (nAMD) with leakage involving the fovea in the study eye prior to Screening, or have a diagnosis of Neovascular Age- Related Macular Degeneration (nAMD) in study eye within 3 months prior to screening and received up to 2 monthly injections of 2 mg aflibercept with last injection approximately 4 weeks prior to Screening” (opens the source at this quote in a new tab)
“Have provided written consent” (opens the source at this quote in a new tab)

Registered exclusion criteria

“Monocular subject or Best Corrected Visual Acuity (BCVA) score of <20 ETDRS letters or 20/400 in fellow eye at Screening” (opens the source at this quote in a new tab)
“Have evidence of a scar, fibrosis, or atrophy of >50% of the total lesion in the study eye.” (opens the source at this quote in a new tab)

Company-described diagnosis window and visual acuity threshold

“To qualify for screening in the SOL-R trial, a subject’s study eye must have had a BCVA of at least 34 ETDRS letters (approximately 20/200 Snellen equivalent vision).” (opens the source at this quote in a new tab)

Diagnosis window: 2024 description of three months

“The trial is intended to randomize approximately 825 subjects who are treatment naïve or diagnosed with wet AMD in the study eye within three months prior to enrollment.” (opens the source at this quote in a new tab)

Retinal thickness stability criteria before randomization

“Subjects maintaining a CSFT of no greater than 350 microns at Weeks -12 and -8, and not experiencing a CSFT increase of greater than 35 microns at Week -8 from their lowest CSFT at any prior visit, received these loading doses at Weeks -8 and -4 prior to randomization on Day 1.” (opens the source at this quote in a new tab)

Enrollment of SOL-1 loading and randomization failures

“Patients enrolled in SOL-R are initially expected to include patients that constitute loading or randomization failures from the SOL-1 study.” (opens the source at this quote in a new tab)

Registered interventions

Arm	Registered intervention description
OTX-TKI Re-dose	“Intravitreal Injection of OTX-TKI”
Aflibercept 2mg on label	“Intravitreal Injection of 2mg of aflibercept”
Aflibercept 8mg high dose	“Intravitreal Injection of 8mg of aflibercept”

Randomized treatment regimens

“Subjects in the first arm of the SOL-R trial received a single dose of AXPAXLI 450 μg at Day 1 and are re-dosed with AXPAXLI 450 μg at Weeks 24, 48, and 72. Subjects in the second arm received aflibercept 2 mg on Day 1 and per label every eight weeks thereafter. Subjects in the third arm received a single dose of aflibercept 8 mg at Day 1 and are re-dosed at Weeks 24, 48, and 72. Subjects will be followed for safety until Week 96. Trial subjects and designated trial personnel will remain masked through the end of Week 96.” (opens the source at this quote in a new tab)

Formulation used in phase 3 trials

“We are currently conducting the SOL-1, SOL-R and HELIOS-3 trials, and we plan to conduct the SOL-X trial and, if needed, the HELIOS-2 trial with a 450 µg axitinib dose of AXPAXLI, or AXPAXLI 450 µg, which is a different formulation than we used in either of the two Phase 1 trials of AXPAXLI that we have completed for the treatment of wet AMD.” (opens the source at this quote in a new tab)

Supplemental aflibercept after randomization

“Subjects in any arm that meet pre-specified rescue criteria will receive a supplemental dose of aflibercept (2 mg).” (opens the source at this quote in a new tab)

Primary endpoint: company definition at Week 56

“The primary endpoint of the SOL-R trial is to demonstrate non-inferiority in mean BCVA change from baseline between the AXPAXLI and on-label aflibercept 2 mg arms at Week 56. The third arm (aflibercept 8 mg) of the SOL-R trial is not part of the non-inferiority analysis at Week 56. Based on FDA guidance, the non-inferiority margin for the lower bound for the trial has been established at -4.5 letters of mean BCVA.” (opens the source at this quote in a new tab)

Primary endpoint: registry definition at Week 48

Field	Registry record
Primary outcome measure	“Best Corrected Visual Acuity (BCVA)”
Description	“Mean change in Best Corrected Visual Acuity (BCVA) from baseline at Week 48”
Time frame	“Week 48”

Primary endpoint: earlier descriptions at one year and Week 48

“The primary endpoint is non-inferiority in mean best corrected visual acuity (BCVA) change from baseline between the AXPAXLI and on-label aflibercept (2 mg) arms at one year.” (opens the source at this quote in a new tab)

“Demonstrate that AXPAXLI is non-inferior to fixed-dose aflibercept 2 mg with respect to mean change in BCVA at Week 48 from baseline in wAMD patients” (opens the source at this quote in a new tab)

Non-inferiority margin based on FDA guidance

“Compare to labeled dosing of Aflibercept 2 mg or Ranibizumab 0.5 mg (-4.5 letter margin)1” (opens the source at this quote in a new tab)
“Primary analysis: AXPAXLI dosed Q24W versus Aflibercept 2mg Q8W” (opens the source at this quote in a new tab)

Company rationale for the Week 56 timepoint

“A singular Week 56 primary endpoint in SOL-R is potentially favorable as subjects will have received their most recent aflibercept or AXPAXLI injection eight weeks prior, at Week 48.” (opens the source at this quote in a new tab)

Company rationale for screening out early persistent fluid

“Screening to exclude subjects with early persistent fluid may be critical for trial success” (opens the source at this quote in a new tab)

Interpretation of rescue injections in non-inferiority trials

“FDA generally does not consider a single rescue as a treatment failure1” (opens the source at this quote in a new tab)
“Rescues in close proximity (<3 months) to the primary endpoint will fall under greater regulatory scrutiny1” (opens the source at this quote in a new tab)

Key secondary endpoint added in 2026: superiority to aflibercept 8 mg at Week 96

“We are amending the trial protocol to add a new key secondary endpoint to evaluate the superiority of AXPAXLI to aflibercept (8 mg) at Week 96.” (opens the source at this quote in a new tab)
“This new key secondary endpoint will be evaluated at Week 96 to align as closely as possible with the aflibercept (8 mg) Year 2 approved dosing interval, which was recently expanded to up to every five months after one year of treatment.” (opens the source at this quote in a new tab)

Secondary endpoints added in 2026: fibrosis and atrophy at Week 96

“To further assess differentiation from aflibercept (2 mg), dosed every eight weeks in the SOL-R trial, we also intend to evaluate the prevention of fibrosis and atrophy through secondary endpoints at Week 96 with the goal of expanding a potential AXPAXLI label in the future.” (opens the source at this quote in a new tab)

Registered secondary outcome measures

No evidence found.

Registry estimated enrollment

Field	Registry record
Enrollment (estimated)	“825”

Planned randomization: approximately 825 subjects (2024)

“Company plans to initiate SOL-R AXPAXLI repeat dosing study (Phase 3, wet AMD) to evaluate repeat dosing of AXPAXLI (450µg) at six months (Q6M) compared to aflibercept (2mg) dosed every eight weeks (Q8W) and a comparator arm dosed Q6M in 825 wet AMD patients.” (opens the source at this quote in a new tab)

Planned randomization: at least 555 subjects (2025)

“Based on current and projected screening, loading, and randomization failure rates observed in SOL-R to date, Ocular believes it has enrolled enough subjects to ensure the Company’s target randomization of at least 555 subjects in SOL-R.” (opens the source at this quote in a new tab)

“Ocular will continue to allow randomization of previously enrolled subjects currently in the loading phase of the trial to maintain its commitment to both patients and investigators, with topline data remaining on track for the first half of 2027.” (opens the source at this quote in a new tab)

Statistical power

“The trial is 90% powered to detect a non-inferiority margin of -4.5 letters of mean BCVA when compared to aflibercept (2 mg) dosed every 8 weeks.” (opens the source at this quote in a new tab)

Randomized participants: 631 (February and June 2026)

“We have completed randomization of the SOL-R trial with 631 subjects randomized.” (opens the source at this quote in a new tab)

“In December 2025, the trial completed the randomization of 631 subjects.” (opens the source at this quote in a new tab)

Randomized participants: 640 (August 2026)

“We have now completed randomization of the SOL-R trial with a total of 640 subjects randomized.” (opens the source at this quote in a new tab)

“In December 2025, the trial completed the randomization of 640 subjects.” (opens the source at this quote in a new tab)

Planned interim safety analysis population

“SOL-R Interim 52-week safety (n >130 patients)” (opens the source at this quote in a new tab)
“SOL-1 52-week safety (n=170 at 52 weeks) plus” (opens the source at this quote in a new tab)

Primary non-inferiority comparison excludes the aflibercept 8 mg arm

“The third arm (aflibercept 8 mg) of the SOL-R trial is not part of the non-inferiority analysis at Week 56.” (opens the source at this quote in a new tab)

Interim safety analysis set

“Ocular plans to conduct an interim safety analysis of patients completing one year in SOL-R during the fourth quarter of 2026 to reach an aggregate of greater than 300 patients with at least one year of treatment across SOL-1 and SOL-R. Because of the interim analysis, SOL-R will incur a 0.0001 alpha penalty during its statistical analysis.” (opens the source at this quote in a new tab)

Efficacy analysis population and handling of rescue injections

No evidence found.

Retention

“Subject retention in the SOL-R trial remains high.” (opens the source at this quote in a new tab)

Discontinuations and reasons

No evidence found.

Topline timing: first half of 2027 (November 2025)

“Ocular will continue to allow randomization of previously enrolled subjects currently in the loading phase of the trial to maintain its commitment to both patients and investigators, with topline data remaining on track for the first half of 2027.” (opens the source at this quote in a new tab)

Topline timing: first quarter of 2027 (February 2026)

“We expect topline data from the SOL-R trial to be available in the first quarter of 2027, an acceleration from our previous guidance of the first half of 2027.” (opens the source at this quote in a new tab)

Topline timing: first quarter of 2028 (June and August 2026)

“Topline data for the SOL-R trial are expected to be available in the first quarter of 2028.” (opens the source at this quote in a new tab)

“This includes maintaining masking of SOL-R to subjects, investigators, and the Company until Week 96 to evaluate new secondary endpoints, with topline data now expected in first quarter of 2028.” (opens the source at this quote in a new tab)

Primary and secondary efficacy results

No evidence found.

Exploratory SOL-1 analysis applying SOL-R rescue criteria: Week 24

“In a prespecified exploratory analysis applying the SOL-R protocol rescue criteria to the SOL-1 results, AXPAXLI demonstrated a 77.1% rescue-free rate at Week 24. Week 24 was selected as the timepoint for this analysis to align with the re-dosing interval being used in the SOL-R trial.” (opens the source at this quote in a new tab)

Post hoc SOL-1 analysis applying SOL-R rescue criteria: Week 52 and treatment burden

“The proportion of SOL-1 patients who would have remained rescue-free under the SOL-R rescue criteria of >5 ETDRS letter loss and ≥75 µm CSFT increase from baseline was 66.5% at Week 52.” (opens the source at this quote in a new tab)
“The total estimated mean injection burden with AXPAXLI represents a 72% reduction counting from the first screening visit at Week -8 excluding loading doses and a 56% reduction when loading doses are included, as compared to a projected on-label dosing regimen of aflibercept (2 mg) with no rescues.” (opens the source at this quote in a new tab)

Planned interim safety analysis in the fourth quarter of 2026

“Ocular remains on track to conduct the interim SOL-R safety analysis and submit the AXPAXLI NDA in the fourth quarter of 2026.” (opens the source at this quote in a new tab)

Adverse events

No evidence found.

Summary

SOL-R has reported no efficacy or safety results as of 2026-09-17; topline data are expected in the first quarter of 2028, and only interim Week 52 safety data are planned for the NDA submission in the fourth quarter of 2026. Company sources report the randomized sample as 631 participants (February and June 2026) and 640 participants (August 2026), both described as completed in December 2025, while the registry still lists an estimated 825 participants. The primary endpoint timepoint is Week 56 in company sources and Week 48 in the registry, which was last updated 2025-06-17, and a 2024 congress presentation. Company descriptions of the rescue criteria changed between May 2025 (loss of at least 10 letters from baseline, or anatomic worsening combined with vision loss) and November 2025 onward (loss of more than 5 letters combined with a CSFT increase of at least 75 µm). The six-month lead-in excluded participants with early persistent fluid or CSFT fluctuation, so the randomized population is enriched for anti-VEGF-responsive disease and may not represent all patients with newly diagnosed neovascular age-related macular degeneration. Supplemental aflibercept is permitted in all arms, so outcomes in the axitinib implant arm will reflect combined exposure in rescued participants. The June 2026 amendment added a key secondary superiority comparison with aflibercept 8 mg and fibrosis and atrophy endpoints after enrollment was complete, and the interim safety analysis carries a 0.0001 alpha penalty.

Registered official title

“A Phase 3b, Multicenter, Open-Label, Extension Study to Evaluate Long-Term Safety of Intravitreal OTX-TKI (Axitinib Implant) in Participants With Neovascular Age-Related Macular Degeneration Who Successfully Completed 2-Year OTX-TKI-2023-AMD-301 or OTX-TKI-2023-AMD-303 Study” (opens the source at this quote in a new tab)

Company-stated primary objectives

“The primary objectives of SOL-X are to evaluate the long-term safety of AXPAXLI; to explore long-term visual outcomes, including visual acuity and the incidence and/or progression of fibrosis and macular atrophy; and to evaluate the impact of delayed initiation of AXPAXLI in patients who initially were randomized to receive aflibercept in either SOL-1 or SOL-R.” (opens the source at this quote in a new tab)

Registry dates and status

Milestone	Registry record
Study start (actual)	“2026-04-27”
Primary completion (estimated)	“2030-08-01”
Study completion (estimated)	“2030-08-01”
Last verified	“2026-06”

Registry sites

“This study has 8 locations” (opens the source at this quote in a new tab)

Site
“California Retina Consultants (CRC)”
“Retina Group of New England”
“Retina Group of Florida - Fort Lauderdale”
“Cumberland Valley Retina Associates”
“Mid Atlantic Retina Specialists”
“Palmetto Retina Center”
“Austin Retina Associates”

Company-reported first enrollment

“In April 2026, the first patient was enrolled in the SOL-X trial, a multi-center, open-label, long-term safety extension clinical trial to evaluate subjects who have completed their two-year safety follow-up visits in either the SOL-1 or SOL-R trial for an additional three years.” (opens the source at this quote in a new tab)

Registered design

Field	Registry record
Allocation	“N/A”
Interventional model	“Single Group Assignment”
Masking	“None (Open Label)”

Company-described design: 36-month open-label extension

“The SOL-X trial (NCT07516132) is a multi-center, 36-month open-label extension trial designed to evaluate the long-term safety, efficacy, and disease modifying potential of AXPAXLI in wet AMD for subjects who have successfully completed their two-year safety follow-up visits in either the SOL-1 or SOL-R trials.” (opens the source at this quote in a new tab)

Visit schedule

“Subjects are assessed at Week 4, Week 12, and then every 12 weeks thereafter. Additional visits can be conducted with supplemental anti-VEGF injection administered based on investigator discretion.” (opens the source at this quote in a new tab)

Registered inclusion criteria

“Participants with a diagnosis of nAMD in the study eye who successfully completed Study OTX-TKI-2023-AMD-301 through Week 104 or Study OTX-TKI-2023-AMD-303 through Week 96” (opens the source at this quote in a new tab)
“Have adequate ocular media and adequate pupillary dilation in the study eye to permit good quality fundus imaging” (opens the source at this quote in a new tab)
“Are able and willing to comply with all study requirements and visits” (opens the source at this quote in a new tab)
“Have provided written informed consent” (opens the source at this quote in a new tab)

Registered exclusion criteria

“Have significant intraocular or periocular infection (bacterial, viral, or fungal) in the study eye within 3 months prior to Day 1” (opens the source at this quote in a new tab)
“History of intraocular inflammation in the study eye” (opens the source at this quote in a new tab)
“Have evidence of a rhegmatogenous retinal detachment or visually significant/severe epiretinal membrane, macular hole, tear of the retinal pigment epithelium in the macula, or other macular” (opens the source at this quote in a new tab)
“Presence of an intercurrent illness or condition that in the opinion of the Investigator, may place the participant at an unacceptable risk, preventing the participant from completing the study or confound the interpretation of study results” (opens the source at this quote in a new tab)

Age

Field	Registry record
Ages eligible for study	“50 Years and older”

Dosing every 24 weeks for all participants

“According to the trial design, all subjects will be given AXPAXLI every 24 weeks, starting at Day 1 (after completion of the Week 104 visit in SOL-1, or Week 96 visit in SOL-R), and again at Weeks 24, 48, 72, 96, and 120.” (opens the source at this quote in a new tab)

“Subjects enrolled in the SOL-X trial will receive AXPAXLI 450 μg every 24 weeks and are to be evaluated at Week 4, Week 12, and every 12 weeks thereafter.” (opens the source at this quote in a new tab)

Registered intervention

“Intravitreal Injection of OTX-TKI” (opens the source at this quote in a new tab)

Registered primary outcome measures

“Incidence and severity of treatment-emergent adverse events (TEAEs) from Baseline (Day 1) through Week 144” (opens the source at this quote in a new tab)
“Proportion of participants with severe vision loss (defined as ≥ 30 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss) from Baseline (Day 1) through Week 144” (opens the source at this quote in a new tab)

Company hypothesis for long-term outcomes

“Ocular believes sustained VEGF suppression with AXPAXLI may reduce the incidence of fibrosis and atrophy in wet AMD, thereby improving long-term outcomes.” (opens the source at this quote in a new tab)

Rationale for delayed-initiation comparison

“SOL-X outcomes may further expand AXPAXLI’s potential by highlighting the need to start AXPAXLI treatment early or risk worse long-term visual outcomes due to potential fibrosis and atrophy that may be seen with pulsatile treatments.” (opens the source at this quote in a new tab)

Secondary outcome measures and definitions of fibrosis and atrophy

No evidence found.

Registry estimated enrollment

Field	Registry record
Enrollment (estimated)	“850”

Company-reported enrollment status

“SOL-X (wet AMD) enrollment continues to accelerate, with the vast majority of trial investigators and eligible patients opting to participate in the open-label extension study.” (opens the source at this quote in a new tab)

Summary

SOL-X is a single-group, open-label extension with no concurrent control and no reported results; its primary outcomes (treatment-emergent adverse events and loss of at least 30 letters through Week 144) are estimated to complete on 2030-08-01. Enrollment is limited to participants who completed 2 years of SOL-1 or SOL-R, which selects for participants who tolerated and remained in the parent trials. Evaluation of delayed initiation compares participants originally randomized to aflibercept with those originally randomized to the axitinib implant, but in SOL-X both groups receive the implant every 24 weeks without masking, and supplemental anti-VEGF injections are permitted at investigator discretion. The registry lists an estimated 850 participants at 8 United States sites, and no definitions of fibrosis or macular atrophy endpoints were identified.

Registered study summary

“Evaluate the safety, tolerability, and efficacy of OTX-TKI for intravitreal use in subjects with Neovascular Age-Related Macular Degeneration” (opens the source at this quote in a new tab)

Company-stated objectives

“In this trial, we evaluated how long we are able to maintain subjects who have been previously treated with anti-VEGF therapy without the need for retreatment.” (opens the source at this quote in a new tab)
“The trial was designed to assess the safety, durability and tolerability of AXPAXLI as well as to assess preliminary biological activity in subjects by measuring anatomical and functional changes.” (opens the source at this quote in a new tab)

Registry dates

Milestone	Registry record
Study start (actual)	“2021-07-28”
Primary completion (actual)	“2023-02-06”
Study completion (actual)	“2023-12-18”
Last update posted	“2024-01-26”

Registry sites

Site location
“Bakersfield, California, United States, 93309”
“Oxnard, California, United States, 93036”
“Altamonte Springs, Florida, United States, 32701”
“St. Petersburg, Florida, United States, 33711”
“Reno, Nevada, United States, 89502”
“The Woodlands, Texas, United States, 77384”

Number of sites and participants

“The clinical trial enrolled a total of 21 subjects at six clinical sites in the United States, who were randomized 3:1 to an arm receiving a single OTX-TKI implant, with a 2 mg aflibercept injection four weeks after implant injection, and an arm receiving aflibercept injections every 8 weeks.” (opens the source at this quote in a new tab)

Interim and final data cutoff dates

Analysis	Data cutoff
7-month interim analysis	“Interim review: data cut off August 24, 2022”

Analysis	Data cutoff
10-month interim analysis	“Interim review: data cut off December 12, 2022”

Analysis	Data cutoff
12-month analysis	“Data cut off April 14, 2023”

Registered design

“A Prospective Multicenter, Double-Masked, Randomized, Parallel-Group, Study to Evaluate the Safety, Tolerability, and Efficacy of OTX-TKI (Axitinib Implant) for Intravitreal Use in Subjects With Neovascular Age-Related Macular Degeneration (nAMD)” (opens the source at this quote in a new tab)

Field	Registry record
Allocation	“Randomized”
Interventional model	“Parallel Assignment”
Interventional model description	“3:1”
Masking	“Triple (ParticipantCare ProviderInvestigator)”

Company-described design and regulatory pathway

“We have conducted a prospective, multi-center, randomized, controlled Phase 1 clinical trial in the United States to evaluate a single 600 µg dose of AXPAXLI with an anti-VEGF injection in comparison with a 2 mg dose of aflibercept. This trial was initiated under an exploratory investigational new drug, or eIND, application, and subsequently transitioned to a traditional investigational new drug, or IND, application.” (opens the source at this quote in a new tab)

Sham injections to maintain masking

“Sham injection was given at Week 0 in the Aflibercept Arm and at Weeks 12, 20, 28, 36 and 44 in the OTX-TKI Arm (not shown).” (opens the source at this quote in a new tab)

Rescue anti-VEGF injection criteria

“Loss of ≥10 letters from best previous BCVA with current BCVA worse than baseline, or” (opens the source at this quote in a new tab)
“Evidence of ≥75μm CSFT increase from previous best value and ≥5 letters loss from best previous BCVA, or” (opens the source at this quote in a new tab)
“New macular hemorrhage” (opens the source at this quote in a new tab)

Follow-up beyond Week 52

“OTX-TKI subjects are followed past Week 52” (opens the source at this quote in a new tab)

Registered inclusion criteria

“Have a diagnosis, within 3 years of screening, of previously treated subfoveal neovascularization (SFNV) secondary to nAMD with leakage involving the fovea, previously treated with documented evidence of an initially favorable clinical response to anti-VEGF therapy (i.e. aflibercept, ranibizumab, brolucizumab, or bevacizumab).” (opens the source at this quote in a new tab)
“The macular appearance on OCT is considered to be free of excess intraretinal and/or subretinal fluid as judged by the investigator.” (opens the source at this quote in a new tab)
“Must have received at least 3 anti-VEGF injections in the past year.” (opens the source at this quote in a new tab)
“Have received the most recent anti-VEGF injection within the past 1-4 weeks prior to screening visit.” (opens the source at this quote in a new tab)
“BCVA ETDRS score between 24 and 83 letters (~20/25 to ~20/320 Snellen equivalent)” (opens the source at this quote in a new tab)

Registered exclusion criteria

“Have evidence of a scar, fibrosis or atrophy of >50% of the total lesion in the study eye” (opens the source at this quote in a new tab)
“Have presence of a disease other than choroidal neovascular membrane (CNVM) due to AMD in the study eye that could affect vision or safety assessments” (opens the source at this quote in a new tab)
“Have monocular vision (fellow eye Snellen BCVA is 20/200 or worse” (opens the source at this quote in a new tab)

Age

Field	Registry record
Ages eligible for study	“50 Years and older”

Population compared with the Australian phase 1 trial

“The population we studied in this U.S.-based clinical trial was different than the population we studied in our Phase 1 clinical trial of AXPAXLI in Australia.” (opens the source at this quote in a new tab)

Axitinib implant 600 µg with aflibercept at Week 4 compared with aflibercept every 8 weeks

“The U.S.-based Phase 1 clinical trial is a prospective, multi-center, randomized, controlled study in subjects previously treated with anti-VEGF therapy that is evaluating a 600 μg dose of OTX-TKI in a single implant, with a 2 mg aflibercept injection four weeks after the implant, compared to 2 mg aflibercept injections administered every 8 weeks.” (opens the source at this quote in a new tab)

Registered interventions

Arm	Registered intervention description
OTX-TKI	“OTX-TKI is one dose so subsequent visits will be sham to maintain the mask”
Aflibercept	“Aflibercept administered every 8 weeks”

Implant characteristics and administration

“Single implant” (opens the source at this quote in a new tab)
“Administered by a 25G needle” (opens the source at this quote in a new tab)
“Target release for 9-12 months” (opens the source at this quote in a new tab)
“Completely bioresorbable” (opens the source at this quote in a new tab)

First-generation formulation differs from the phase 3 formulation

“We are currently conducting the SOL-1, SOL-R and HELIOS-3 trials, and we plan to conduct the SOL-X trial and, if needed, the HELIOS-2 trial with a 450 µg axitinib dose of AXPAXLI, or AXPAXLI 450 µg, which is a different formulation than we used in either of the two Phase 1 trials of AXPAXLI that we have completed for the treatment of wet AMD. This optimized configuration provides for an increased daily release of the drug and improved synchronization of axitinib drug release with hydrogel bioresorption.” (opens the source at this quote in a new tab)

Registered primary outcome measure

Field	Registry record
Outcome measure	“Safety and Tolerability”
Description	“Incidence and severity of treatment emergent adverse events”
Time frame	“Through study completion, an average of 1 year”

Registered secondary outcome measures

Outcome measure	Registered description
BCVA changes	“BCVA Changes from Baseline”
Central subfield thickness changes	“Central subfield thickness changes from baseline”
Rescue therapy	“Proportion of subjects receiving rescue therapy”
Absence of fluid	“Proportion of subjects with absence of foveal fluid”
Number of injections	“Number of injections from baseline”

Measures of biological activity

“The trial is designed to assess the safety, durability and tolerability of OTX-TKI, and to assess biological activity in subjects by measuring best corrected visual acuity (BCVA) and central subfield thickness (CSFT) of the retina.” (opens the source at this quote in a new tab)

Definition of reduction in treatment burden

“Overall, a 92% reduction in treatment burden (average percent decrease in injections over the period compared to a standard monthly injection regimen) was observed in AXPAXLI treated subjects for up to 10 months.” (opens the source at this quote in a new tab)

“Reduction in treatment burden calculation includes all rescue injections” (opens the source at this quote in a new tab)

Registry enrollment

Field	Registry record
Enrollment (actual)	“21”

Participants by arm and analysis

“The trial enrolled a total of 21 subjects at six clinical sites, comprising two arms consisting of subjects previously treated with, and who were responsive to, standard of care anti-VEGF therapy: a 16-subject arm receiving AXPAXLI in combination with a single anti-VEGF injection at month one and a five-subject arm receiving on-label aflibercept at eight-week intervals.” (opens the source at this quote in a new tab)
“Since this subject was not treated according to protocol, the subject was excluded from the analysis of biological activity, which comprised 15 out of the 16 subjects in the AXPAXLI arm and all five subjects in the aflibercept arm, but the subject was included in the safety analysis which comprised all 16 subjects in the AXPAXLI arm and all five subjects in the aflibercept arm.” (opens the source at this quote in a new tab)

Participants analyzed after censoring rescued participants

“Sample size for OTX-TKI (censoring rescued subjects): n=15 at Baseline and Weeks 4 and 12; n=14 at Week 8 (missed visit) and Weeks 16 and 20; n=12 at Week 24 and n=11 at Weeks 28, 32, 36 and 40; n=10 at Week 44; n=9 at Weeks 48 and 52” (opens the source at this quote in a new tab)

Exclusion of one participant from the efficacy analysis

“There was one subject randomized to the AXPAXLI arm who was inadvertently given aflibercept instead of sham injections at the subject’s month three and month five visits.” (opens the source at this quote in a new tab)

Per protocol analysis and rescue-free rate calculation

“Data cut off April 14, 2023; per protocol analysis” (opens the source at this quote in a new tab)
“Rescue-free rate calculations: If subjects received rescue anti-VEGF therapy at a study visit, those were reflected to count at the following study visit in the graph above” (opens the source at this quote in a new tab)
“Percentages presented in the graph above represent rescue-free rates up to each study visit, except for the 33% at Week 52 which includes rescue injections given at the Week 52 study visit” (opens the source at this quote in a new tab)

Statistical testing

No evidence found.

No dropouts through the 12-month data cutoff

“There were no retinal detachment, retinal vasculitis, or implant migration into the anterior chamber adverse events observed in the OTX-TKI arm, and no subjects had dropped out of either arm as of the data cutoff.” (opens the source at this quote in a new tab)

Trial completion

“All enrolled subjects have completed this Phase 1 clinical trial.” (opens the source at this quote in a new tab)

Missed visits

“n=14 in OTX-TKI arm at Weeks 8, 28, 40 and 48 due to missed visits” (opens the source at this quote in a new tab)

Safety population, data cutoff April 14, 2023

Characteristic	Axitinib implant 600 µg (N=16)	Aflibercept 2 mg every 8 weeks (N=5)
Mean (SD) age, years	“76 (8)”	“84 (8)”
Male, n (%)	“8 (50)”	“3 (60)”
Female, n (%)	“8 (50)”	“2 (40)”
Mean (SD) months since wet AMD diagnosis	“18 (12)”	“18 (12)”
Mean (SD) number of anti-VEGF injections within 12 months prior to baseline (annualized)	“8 (3)”	“8 (4)”
Mean (SD) BCVA, ETDRS letters	“70.9 (17.7)”	“73.8 (9.0)”
Mean (SD) CSFT, µm	“273.8 (43.0)”	“240.6 (29.6)”

Efficacy population baseline BCVA and CSFT

“Mean baseline CSFT” (opens the source at this quote in a new tab)
“OTX-TKI: 269.2 (40.3) μm” (opens the source at this quote in a new tab)
“Aflibercept Q8W: 240.6 (29.6) μm” (opens the source at this quote in a new tab)
“Mean baseline BCVA” (opens the source at this quote in a new tab)
“OTX-TKI: 73.7 (14.4) letters” (opens the source at this quote in a new tab)
“Aflibercept Q8W: 73.8 (9.0) letters” (opens the source at this quote in a new tab)

Week 52 mean change in BCVA and CSFT

Outcome, mean (SD) change from baseline to Week 52	Axitinib implant 600 µg (n=15)	Axitinib implant 600 µg, censoring rescued participants	Aflibercept 2 mg every 8 weeks (n=5)
BCVA, letters	“OTX-TKI: -1.0 (6.0) letters”	“OTX-TKI: +0.6 (2.6) letters”	“Aflibercept 2mg Q8W: +2.0 (7.2)”
CSFT, µm	“OTX-TKI: +20.2 (41.6) μm”	“OTX-TKI: +17.2 (47.6) μm”	“Aflibercept 2mg Q8W: -2.2 (8.5)”

Rescue-free participants in the axitinib implant arm up to each visit (n=15)

Visit	Rescue-free, %	Rescue-free, n/N
Week 8	“100%”	“15/15”
Week 12	“100%”	“15/15”
Week 16	“93%”	“14/15”
Week 20	“93%”	“14/15”
Week 24	“80%”	“12/15”
Week 28	“73%”	“11/15”
Week 32	“73%”	“11/15”
Week 36	“73%”	“11/15”
Week 40	“73%”	“11/15”
Week 44	“67%”	“10/15”
Week 48	“67%”	“10/15”
Week 52	“60%”	“9/15”

Rescue-free rate including rescue injections given at the Week 52 visit

“33% inclusive of Week 52” (opens the source at this quote in a new tab)
“Percentages presented in the graph above represent rescue-free rates up to each study visit, except for the 33% at Week 52, which includes rescue injections given at the Week 52 study visit.” (opens the source at this quote in a new tab)

Month 12 rescue and treatment burden reduction

“60% of OTX-TKI subjects were rescue-free up to Month 12. At the Month 12 visit, an additional four of the subjects were rescued. Overall, an 89% reduction in treatment burden was observed in OTX-TKI treated subjects at 12 months.” (opens the source at this quote in a new tab)
“Approximately 73% of patients either required no or only one supplemental anti-VEGF injection through Month 12, which is clinically meaningful and highlights the possibility of OTX-TKI being widely adopted in the management of wet AMD.” (opens the source at this quote in a new tab)

No rescue injections meeting protocol criteria before 6 months

“100% Rescue Free Per Protocol up to 6 months1” (opens the source at this quote in a new tab)

Injections compared with the year before baseline and with aflibercept

“There were fewer injections over 52 weeks in subjects with AXPAXLI compared with the annualized number of anti-VEGF injections in 52 weeks prior to baseline. Furthermore, there were fewer injections over 52 weeks received in subjects from AXPAXLI treatment compared to those received in aflibercept 2 mg treatment arm.” (opens the source at this quote in a new tab)

Month 10 interim analysis

Outcome, mean (SD) change from baseline to Month 10	Axitinib implant 600 µg	Axitinib implant 600 µg, censoring rescued participants	Aflibercept 2 mg every 8 weeks
BCVA, letters	“OTX-TKI: -0.3 (5.1) letters”	“OTX-TKI: -0.1 (5.3) letters”	“Aflibercept Q8W: -0.8 (2.8) letters”
CSFT, µm	“OTX-TKI: -1.3 (23.7) μm”	“OTX-TKI: -2.1 (26.9) μm”	“Aflibercept Q8W: -4.5 (4.4) μm”

“Treatment Reduction” (opens the source at this quote in a new tab)
“Up to 10 Months: 92%” (opens the source at this quote in a new tab)

“92% reduction in anti-VEGF treatment burden in OTX-TKI patients up to 10 months” (opens the source at this quote in a new tab)

Rescues up to Month 10 initiated at investigator discretion

“Four subjects were rescued in the AXPAXLI arm up to Month 10. One subject, the subject who experienced endophthalmitis, was rescued twice. None of these rescues met the pre-established rescue criteria set forth in the clinical trial protocol and were instead initiated at investigator discretion. One additional subject, who met the established rescue criteria at such subject’s Month 10 visit, was rescued at the end of Month 10.” (opens the source at this quote in a new tab)

Month 7 interim analysis

“Mean change in CSFT from baseline to Month 7:” (opens the source at this quote in a new tab)
“OTX-TKI: +9.2 (38.6) μm” (opens the source at this quote in a new tab)
“Aflibercept: +0.4 (9.1) μm” (opens the source at this quote in a new tab)
“Mean change in BCVA from baseline to Month 7:” (opens the source at this quote in a new tab)
“OTX-TKI: -1.3 (5.2) letters” (opens the source at this quote in a new tab)
“Aflibercept: -1.0 (5.3) letters” (opens the source at this quote in a new tab)
“80% of subjects were rescue-free up to 6 months and 73% of subjects were rescue-free up to 7 months” (opens the source at this quote in a new tab)

Hydrogel bioresorption timing: about 9 months (10-month analysis)

“Interim data suggests OTX-TKI 0.6mg hydrogel implant bioresorbs at an average of ~9 months” (opens the source at this quote in a new tab)

Hydrogel bioresorption timing: about 8 to 9 months (12-month analysis)

“We are encouraged by the 12-month data as the performance of the OTX-TKI drug product continued to demonstrate that the implant bioresorbs at an average of about eight to nine months with axitinib remaining longer in the eye, potentially providing a window to re-dose patients before disease reactivation starts” (opens the source at this quote in a new tab)

Variability in CSFT over 52 weeks

CSFT standard deviation quartile	Brolucizumab phase 3 trials HAWK and HARRIER (N=1752), Week 12 to Week 96	Axitinib implant (N=15), baseline to Week 52
Q1	“<8”	“<9”
Q2	“8-18”	“9-17”
Q3	“18-39”	“17-33”
Q4	“>39”	“>33”

Adverse events in the study eye at 12 months (data cutoff April 14, 2023)

Event, n (%)	Axitinib implant 600 µg (N=16)	Aflibercept 2 mg every 8 weeks (N=5)
Elevated IOP	“2 (12.5)”	“1 (20.0)”
Retinal detachment	“0”	“0”
Retinal vasculitis	“0”	“0”
Implant migration into the anterior chamber	“0”	“N/A”
Acute endophthalmitis	“1 (6.25)”	“0”
Ocular AEs	“16 (100.0)”	“3 (60.0)”
Mild	“14 (87.5)”	“2 (40.0)”
Moderate	“2 (12.5)”	“1 (20.0)”
Severe	“0”	“0”
SAEs	“1 (6.25)”	“0”

Serious adverse event percentage reported as 12.5% (June 2023 presentation)

“Serious AEs 1 (12.5)* 0” (opens the source at this quote in a new tab)

Endophthalmitis after protocol-mandated aflibercept injection

“aModerate and serious ocular AE in OTX-TKI arm was acute endophthalmitis 6 days after mandated aflibercept injection at Month 1.” (opens the source at this quote in a new tab)
“Injection procedure related, unrelated to study drug” (opens the source at this quote in a new tab)
“Resolved after IVT antibiotic injection, with vision returning to baseline” (opens the source at this quote in a new tab)

Moderate events other than endophthalmitis

“Acute endophthalmitis SAE (moderate and resolved) and worsening of cataract (moderate) in OTX-TKI arm” (opens the source at this quote in a new tab)
“Elevated IOP in aflibercept arm (moderate and resolved)” (opens the source at this quote in a new tab)

Elevated intraocular pressure: none in the axitinib implant arm at the 10-month cutoff

“There were no instances of elevated intraocular pressure, or IOP, retinal detachment, retinal vasculitis, or hydrogel implant migration into the anterior chamber observed in the AXPAXLI arm, and no subjects had dropped out of either arm as of the data cutoff.” (opens the source at this quote in a new tab)

“Elevated IOP 0 1” (opens the source at this quote in a new tab)
“1Interim review: data cut off December 12, 2022: includes n=4 subjects in the OTX-TKI arm past Month 12” (opens the source at this quote in a new tab)

Drug-related serious adverse events

“As of the data cutoff of April 14, 2023, there were no drug-related ocular or systemic serious adverse events (SAEs) observed in the OTX-TKI arm.” (opens the source at this quote in a new tab)

Systemic pharmacokinetics

No evidence found.

Summary

OTX-TKI-2020-101 randomized 21 participants (16 axitinib implant, 5 aflibercept), and efficacy analyses included 15 implant participants after one participant received aflibercept instead of sham injections at Months 3 and 5; no statistical comparisons, peer-reviewed publication, or registry results were identified. All implant participants received protocol-mandated aflibercept at Month 1, so outcomes reflect combination exposure rather than implant monotherapy, and the population was limited to previously treated, anti-VEGF-responsive eyes without excess fluid. The trial used a first-generation 600 µg implant, whereas phase 3 trials use a different 450 µg formulation. Sources disagree on elevated IOP in the implant arm: none at the December 12, 2022 cutoff (10-K and 10-month presentation) and 2 of 16 participants (12.5%) at the April 14, 2023 cutoff; the serious adverse event percentage for the single endophthalmitis event is reported as 12.5% in the June 2023 presentation and 6.25% in the October 2024 presentation. Reported bioresorption time was about 9 months at the 10-month analysis and about 8 to 9 months at the 12-month analysis. No systemic pharmacokinetic data were reported for this trial.

Independent review notes a waning implant effect near week 52 and protocol aflibercept exposure

“By week 48, 67% of AXPAXLI-treated patients remained rescue-free, but this declined to 33% by week 52, suggesting a waning therapeutic effect near the end of the implant’s duration of action.” (opens the source at this quote in a new tab)
“In the OTX-TKI arm, patients received 0.6 mg OTX-TKI at week zero followed by aflibercept 2 mg at week 4. Patients then received sham injections every 8 weeks through week 52.” (opens the source at this quote in a new tab)

Registered study summary

“To evaluate the safety, tolerability and efficacy of OTX-TKI for intravitreal use, in subjects who have neovascular age-related macular degeneration (AMD).” (opens the source at this quote in a new tab)

Research question and objectives

“Research Question: Does axitinib (tyrosine kinase inhibitor) have biological activity in wet AMD subjects with retinal fluid when administered intravitreally?” (opens the source at this quote in a new tab)

“This Phase 1 clinical trial was designed to evaluate the safety, durability and tolerability of AXPAXLI.” (opens the source at this quote in a new tab)
“In this trial, we evaluated whether AXPAXLI can reduce existing fluid levels.” (opens the source at this quote in a new tab)

Registry dates

Milestone	Registry record
Study start (actual)	“2019-02-18”
Primary completion (actual)	“2024-01-10”
Study completion (actual)	“2024-01-10”
Last update posted	“2024-07-10”

Regulatory submission in Australia

“Our Phase 1 clinical trial of AXPAXLI in Australia was submitted to the Therapeutic Goods Administration, Australia’s regulatory authority for therapeutic goods, in July 2018 and was being conducted at multiple sites in Australia.” (opens the source at this quote in a new tab)

Number of sites: six in the registry

“This study has 6 locations” (opens the source at this quote in a new tab)

Number of sites: five in the 2021 presentation

“5 sites in Australia” (opens the source at this quote in a new tab)

Interim data cutoff dates

Presentation	Data cutoff
ARVO 2021	“Data cut on April 12th, 2021”

Presentation	Data cutoff
AAO 2021	“Data cut off October 15, 2021”

Presentation	Data cutoff
Angiogenesis, Exudation, and Degeneration 2022	“Data cut off January 11, 2022”

Presentation	Data cutoff
AAO 2022	“Data cut off August 5, 2022”

Registered design

“A Phase 1 Open-Label, Dose Escalation Study of OTX-TKI for Intravitreal Use in Subjects With Neovascular Age-Related Macular Degeneration (AMD)” (opens the source at this quote in a new tab)

Field	Registry record
Allocation	“Randomized”
Interventional model	“Sequential Assignment”
Masking	“None (Open Label)”

Company-described design

“We have conducted an open-label, multi-center, proof-of-concept, dose-escalation Phase 1 clinical trial of AXPAXLI for the treatment of patients with wet AMD.” (opens the source at this quote in a new tab)

Dose cohorts, data and safety monitoring committee review, and follow-up

“Cohort 2; 400 μg” (opens the source at this quote in a new tab)
“(2 x 200μg implants); N=7” (opens the source at this quote in a new tab)
“Cohort 1; 200 μg” (opens the source at this quote in a new tab)
“(1 x 200μg implant); N=6” (opens the source at this quote in a new tab)
“Cohort 3a; 600 μg” (opens the source at this quote in a new tab)
“(3 x 200μg implants); N=6” (opens the source at this quote in a new tab)
“Cohort 3b; 400 μg” (opens the source at this quote in a new tab)
“(2 x 200μg implants) + anti-VEGF; N=4” (opens the source at this quote in a new tab)
“Cohort 4a*; 600 μg single implant; N=1” (opens the source at this quote in a new tab)
“Cohort 4b*; 600 μg single implant + anti-VEGF ; N=5” (opens the source at this quote in a new tab)

“Monthly Follow-up to Month 17” (opens the source at this quote in a new tab)

Rescue criteria

“If needed, any subject in any treatment arm may receive rescue therapy (i.e., anti-VEGF) at the investigator’s discretion regardless of meeting rescue criteria” (opens the source at this quote in a new tab)
“The following criteria were used to identify subjects who will likely require rescue therapy: 1) loss of ≥15 letters from best previous BCVA due to AMD, with current BCVA not better than baseline; or 2) loss of ≥10 letters on 2 consecutive visits from best previous BCVA due to AMD, with current BCVA score not better than baseline; or 3) evidence of worsening disease activity manifest by >75 microns CSFT from previous best value” (opens the source at this quote in a new tab)

Registered inclusion criteria

“Are at least 50 years of age” (opens the source at this quote in a new tab)
“Are eligible for standard therapy” (opens the source at this quote in a new tab)
“Have active primary CNVM secondary to AMD, either newly diagnosed or previously treated with documented response to anti-VEGF therapy in the study eye [primary subfoveal CNV secondary to AMD including juxtafoveal lesions that affect the fovea] documented by FA and SD-OCT” (opens the source at this quote in a new tab)

Registered exclusion criteria

“Have previous laser photocoagulation to the center of the fovea in the study eye” (opens the source at this quote in a new tab)
“Have participated in any study involving an investigational drug either in the U.S. or outside the U.S. within the past 30 days” (opens the source at this quote in a new tab)
“Have a presence of a disease other than CNVM due to AMD in the study eye that could affect vision or safety assessments” (opens the source at this quote in a new tab)

Pre-existing retinal fluid required

“Presence of retinal fluid” (opens the source at this quote in a new tab)

“The Phase 1 clinical trial was comprised of four cohorts consisting of subjects with wet AMD and pre-existing intraretinal and/or subretinal fluid” (opens the source at this quote in a new tab)

Dose cohorts

“The Phase 1 clinical trial was comprised of four cohorts consisting of subjects with wet AMD and pre-existing intraretinal and/or subretinal fluid: a lower dose cohort of 200 µg with six subjects; a higher dose cohort of 400 µg with seven subjects; a third cohort with two parallel arms, one arm of four subjects receiving a concomitant anti-VEGF injection with 400 µg of AXPAXLI and the other arm of six subjects receiving a 600 µg of AXPAXLI with no anti-VEGF injection; and a fourth cohort with two parallel arms, one arm of one subject receiving a 600 µg single dose of AXPAXLI and the other arm of five subjects receiving a 600 µg single dose of AXPAXLI with anti-VEGF injection.” (opens the source at this quote in a new tab)

Implant configuration

“Cohorts 1-3 used one to three 0.2 mg (200 μg) implants to achieve different dose levels (0.2, 0.4 and 0.6 mg)” (opens the source at this quote in a new tab)

“OTX-TKI is a dried polyethylene glycol-based hydrogel fiber containing dispersed microcrystals of a small molecule tyrosine kinase inhibitor (TKI).” (opens the source at this quote in a new tab)

Registered anti-VEGF agents for combination cohorts

Field	Registry record
Anti-VEGF description	“Standard of care therapy used to block vascular endothelial growth factor”
Other names	“aflibercept”
Other names	“bevacizumab”
Other names	“ranibizumab”

Formulation compared with phase 3 trials

“We conducted the two Phase 1 trials of AXPAXLI for the treatment of wet AMD with different formulations of axitinib.” (opens the source at this quote in a new tab)

Registered primary outcome measure

Field	Registry record
Outcome measure	“Incidence of treatment emergent adverse events for each subject”
Description	“All adverse events from screening through end of study will be captured”
Time frame	“9 months”

Registered secondary outcome measure: maximum tolerated dose

“A Central Reading Center will evaluate multiple imaging modalities to confirm evidence of biological activity for subjects that have been treated with the OTX-TKI injection. If all subjects tolerate lower dosages, additional subjects will be treated at higher dosages. All data will be evaluated by the DSMC who, in concert with the Medical Monitor, will determine the Maximally Tolerated Dose.” (opens the source at this quote in a new tab)

Biological activity measures

“Biological activity: mean change in central subfield thickness measured by SD-OCT, BCVA, and clinically-significant leakage on FA and/or OCT-A” (opens the source at this quote in a new tab)

“In the Phase 1 clinical trial of AXPAXLI conducted in Australia, we evaluated biological activity by measuring CSFT, using spectral domain optical coherence tomography, or OCT, and following visual acuity over time as measured by BCVA.” (opens the source at this quote in a new tab)

Registry enrollment

Field	Registry record
Enrollment (actual)	“29”

Participants dosed

“29 subjects dosed with OTX-TKI” (opens the source at this quote in a new tab)

Participants in the published interim analyses (cohorts 1 to 3)

“Cohorts 1-3 Subjects” (opens the source at this quote in a new tab)
“(Pooled; N=23)” (opens the source at this quote in a new tab)

Participants remaining in follow-up by cohort (January 2022)

“Cohort 1: n=6 until Month 9; Cohort 2: n=7 until Month 12, n=6 for Month 14, n=5 for Month 16 and 17” (opens the source at this quote in a new tab)
“Cohort 3a: n=6 until Month 11, n=5 for Month 12, n=2 for Month 14, n=1 for Month 16 and 17; Cohort 3b: n=4 until Month 7.5; n=3 for Month 9, n=2 for Month 11 to 14; n=1 for Month 16” (opens the source at this quote in a new tab)

Interim, unmonitored data

“NOTE: Interim review, unmonitored data; Data cut off August 5, 2022” (opens the source at this quote in a new tab)

Rescue counting rule

“If subjects received rescue anti-VEGF therapy at a study visit, they were counted as rescued at the following study visit in the table above.” (opens the source at this quote in a new tab)

Analysis of cohort 4 and final analysis

No evidence found.

Trial completion

“All subjects have completed this Phase 1 clinical trial.” (opens the source at this quote in a new tab)

Discontinuations and reasons

No evidence found.

Cohorts 1 to 3, data cutoff January 11, 2022

Characteristic	Cohort 1, 200 µg (n=6)	Cohort 2, 400 µg (n=7)	Cohort 3a, 600 µg (n=6)	Cohort 3b, 400 µg plus anti-VEGF (n=4)	All participants (n=23)
Age, years, mean (SD)	“75.8 (3.7)”	“74.7 (5.4)”	“77.3 (5.4)”	“78.3 (8.1)”	“76.2 (5.3)”
Male, n (%)	“5 (83.3%)”	“4 (57.1%)”	“5 (83.3%)”	“3 (75.0%)”	“17 (73.9%)”
Female, n (%)	“1 (16.7%)”	“3 (42.9%)”	“1 (16.7%)”	“1 (25.0%)”	“6 (26.1%)”
BCVA, ETDRS letters (Snellen equivalent), mean ± SEM	“48 (20/110) ± 12.0”	“62 (20/63) ± 8.5”	“46 (20/125) ± 6.4”	“47 (20/125) ± 11.8”	“51 (20/100) ± 4.7”
CSFT, µm, mean ± SEM	“680 ± 159”	“450 ± 29”	“521 ± 68”	“435 ± 58”	“526 ± 49”

Treatment history by subgroup

“Baseline CSFT and BCVA ± SEM for treatment naïve subjects was 571 ± 88.7 μm and 46 ± 5.6 letters, respectively. Baseline CSFT and BCVA ± SEM for previously treated subjects was 485 ± 47.6 μm and 57 ± 7.4 letters, respectively.” (opens the source at this quote in a new tab)

“Number of treatment-naïve subjects in each cohort. Cohort 1 (n=2), Cohort 2 (n=2), Cohort 3a (n=5), and Cohort 3b (n=2)” (opens the source at this quote in a new tab)

Month 6 change in CSFT and BCVA (data cutoff August 5, 2022)

Population	Baseline CSFT	Change in CSFT at Month 6	Baseline BCVA	Change in BCVA at Month 6
All participants (n=23)	“526 ± 49 μm”	“-101.3 ± 32.0 μm”	“51 ± 5 letters”	“+1.1 ± 2.0 letters”
Treatment-naive participants (n=11)	“571 ± 89 μm”	“-143.2 ± 45.6 μm”	“46 ± 6 letters”	“+2.6 ± 3.6 letters”

Participants without rescue anti-VEGF injections by cohort (data cutoff January 11, 2022)

Cohort	Month 1	Month 3	Month 6	Month 7.5	Month 9	Month 12
Cohort 1 (200 µg)	“100% (6/6)”	“67% (4/6)”	“50% (3/6)”	“50% (3/6)”	“50% (3/6)”	“NA”
Cohort 2 (400 µg)	“86% (6/7)”	“71% (5/7)”	“57% (4/7)”	“43% (3/7)”	“43% (3/7)”	“29% (2/7)”
Cohort 3a (600 µg)	“100% (6/6)”	“83% (5/6)”	“83% (5/6)”	“50% (3/6)”	“17% (1/6)”	“20% (1/5)*”
Cohort 3b (400 µg plus anti-VEGF)	“100% (4/4)”	“100% (4/4)”	“50% (2/4)”	“50% (2/4)”	“33% (1/3)*”	“0% (0/2)*”
All cohorts (pooled)	“96% (22/23)”	“78% (18/23)”	“61% (14/23)”	“48% (11/23)”	“36% (8/22)*”	“21% (3/14)*”

Earlier rescue-free rates in cohort 3a at Month 6: 66.6% (October 2021)

“Cohort 3a” (opens the source at this quote in a new tab)
“(600 μg)* 83.3 (5/6) 83.3 (5/6) 66.6 (4/6) 66.6 (4/6) 40 (2/5)* 100 (1/1)* 100 (1/1)* TBD” (opens the source at this quote in a new tab)
“OVER 50% OF SUBJECTS DID NOT RECEIVE ANTI-VEGF THERAPY OUT TO 6 MONTHS” (opens the source at this quote in a new tab)

Rescue-free rates at 6 months by cohort (August 2022)

“Cohort 1 50% of subjects rescue-free up to 6 months” (opens the source at this quote in a new tab)
“Cohort 2 57% of subjects rescue-free up to 6 months” (opens the source at this quote in a new tab)
“Cohort 3a 83% of subjects rescue-free up to 6 months” (opens the source at this quote in a new tab)
“Cohort 3b 50% of subjects rescue-free up to 6 months” (opens the source at this quote in a new tab)
“Over ~60% of all subjects did not receive anti-VEGF rescue injections for 6 months” (opens the source at this quote in a new tab)

Median time to first rescue

“After treatment with OTX-TKI, median time to first rescue with anti-VEGF was 7 months” (opens the source at this quote in a new tab)

Duration of activity and early fluid reduction

“Some subjects showed a decrease in intraretinal or subretinal fluid by two months in cohorts 2 (400 µg) and 3a (600 µg). In cohort 3b (400 µg dose plus anti-VEGF induction injection of aflibercept), two subjects showed a decrease in intraretinal or subretinal fluid as early as a week after treatment. We observed extended duration of activity of six months or more for over 60% of subjects across all cohorts and for over 80% of subjects in cohort 3a, in which we administered a 600 μg dose.” (opens the source at this quote in a new tab)

“Approximately 50% of all subjects showed durability of 7.5 months or longer” (opens the source at this quote in a new tab)

Implant biodegradation and movement

“In addition, the AXPAXLI doses in cohort 1 (200 µg single dose) were observed to have biodegraded in all subjects within nine to 10.5 months of injection. It has also been observed in the trial that the hydrogels were able to be adequately monitored and that there was limited to no movement of the hydrogel and no migration into the anterior chamber has occurred.” (opens the source at this quote in a new tab)

Results for cohort 4 (600 µg single implant with or without anti-VEGF)

No evidence found.

Adverse events in the study eye by cohort (data cutoff August 5, 2022)

Event, n	Cohort 1, 200 µg (n=6)	Cohort 2, 400 µg (n=7)	Cohort 3a, 600 µg (n=6)	Cohort 3b, 400 µg plus anti-VEGF (n=4)	Total (n=23)
Vitreous floaters	“0”	“1”	“0”	“2”	“3”
Endophthalmitis	“0”	“0”	“0”	“0”	“0”
Retinal detachment	“0”	“0”	“0”	“0”	“0”
Implant migration into anterior chamber	“0”	“0”	“0”	“0”	“0”
Elevated IOP	“0”	“0”	“0”	“0”	“0”
Ocular inflammation	“0”	“0”	“0”	“1”	“1”
Subconjunctival hemorrhage	“1”	“3”	“5”	“4”	“13”
Eye pain	“0”	“2”	“2”	“0”	“4”
Worsening cataract	“0”	“1”	“2”	“1”	“4”
Pigmented keratic precipitates	“3”	“0”	“0”	“0”	“3”
Dry eye	“1”	“0”	“1”	“1”	“3”

Ocular adverse events by maximum severity (data cutoff August 5, 2022)

“Ocular AEs 4 7 6 3 20” (opens the source at this quote in a new tab)
“Mild 4 4 3 2 13” (opens the source at this quote in a new tab)
“Moderate 0 3 2 1 6” (opens the source at this quote in a new tab)
“Severe 0 0 1a 0 1a” (opens the source at this quote in a new tab)
“Serious AEs 0 0 0 0 0” (opens the source at this quote in a new tab)
“a Severe ocular AE in Cohort 3a was worsening of cataract” (opens the source at this quote in a new tab)

Adverse event counts and serious non-ocular events (data cutoff October 15, 2021)

“Adverse Events (AEs) 14 27 31 13 85” (opens the source at this quote in a new tab)
“Suspected Relationship to Study Product 1 2 3 3 9” (opens the source at this quote in a new tab)
“Suspected Relationship to Injection Procedure 1 5 10 4 20” (opens the source at this quote in a new tab)
“Ocular AEs (Study Eye) 6 15 20 9 50” (opens the source at this quote in a new tab)
“Serious Ocular AEs 0 0 0 0 0” (opens the source at this quote in a new tab)
“Serious Non-ocular AEs† 1 0 1 0 2” (opens the source at this quote in a new tab)
“† Serious non-ocular AEs: atrial fibrillation (Cohort 1) and ureterovesical stone (Cohort 3a)” (opens the source at this quote in a new tab)
“‡ Severe AE: ureterovesical stone” (opens the source at this quote in a new tab)

Uveitis and implant affecting vision (data cutoff October 15, 2021)

“No IOP elevations were reported” (opens the source at this quote in a new tab)
“Uveitis was reported in one subject (Cohort 3b) which resolved with treatment” (opens the source at this quote in a new tab)
“OTX-TKI implant affecting vision 0 1 3 0 4” (opens the source at this quote in a new tab)

Vitreous floaters count in January 2022

“Vitreous floaters 0 1 0 1 2” (opens the source at this quote in a new tab)

Drug-related serious adverse events over 9 months

“In the clinical trial, intravitreal injections of AXPAXLI at 200 μg, 400 μg, and 600 μg, with and without concurrent administration of anti-VEGF, were generally well tolerated. There were no drug-related serious treatment-emergent adverse events reported in any of the AXPAXLI dose cohorts over the 9-month study period.” (opens the source at this quote in a new tab)

Systemic pharmacokinetics: plasma axitinib below the limit of quantification

“Plasma concentrations of axitinib were below the limit of quantification of assay (BLQ) <0.1 ng/ml at all sampled timepoints in all subjects in Cohorts 1, 2, 3a and 3b” (opens the source at this quote in a new tab)

“Plasma levels of the active drug, axitinib, were below the limit of quantification at all doses, indicating that systemic exposure to intravitreal delivery of axitinib by AXPAXLI up to 600 μg was negligible.” (opens the source at this quote in a new tab)

Summary

CLN-0046 was an open-label, uncontrolled, dose-escalation trial; efficacy and safety were presented only as interim, unmonitored analyses of cohorts 1 to 3 (23 of 29 participants), and no results for cohort 4 (6 participants), no final analysis, no peer-reviewed publication, and no registry results were identified. Cohort sizes were 4 to 7 participants, cohorts mixed treatment-naive and previously treated eyes, and rescue anti-VEGF injections could be given at investigator discretion without meeting rescue criteria. The trial used first-generation implants (one to three 200 µg implants in cohorts 1 to 3), which differ from the 450 µg formulation used in phase 3 trials. Reported values changed across data cutoffs: the Month 6 rescue-free rate in cohort 3a was 66.6% (4 of 6) in October 2021 and 83% (5 of 6) in January 2022; the severe adverse event was attributed to a ureterovesical stone in October 2021 and to worsening cataract in the study eye in a 2023 presentation; vitreous floaters totaled 2 in January 2022 and 3 in August 2022. The registry lists 6 sites, whereas a 2021 presentation lists 5. Plasma axitinib was below the limit of quantification (less than 0.1 ng/mL) in cohorts 1 to 3.