APEX Study Phase 1b Results on KSI-101 for Macular Edema

Bispecific trap-antibody inhibiting interleukin-6 and vascular endothelial growth factor (KSI-101): Week 24 Results From the Phase 1b APEX Study in Patients with Macular Edema Secondary to Inflammation (MESI) Dolly Chang 1 ; Allen Hu 2 ; Charles Wykoff 3 ; David Almeida 4 ; Melina Cavichini Cordeiro 1 , Scott Fitzpatrick 1 ; Victor Perlroth 1 ; J. Pablo Velazquez-Martin 1 1 Kodiak Sciences, Palo Alto, United States; 2 Cumberland Valley Retina Consultants, Hagerstown, US; 3 Blanton Eye Institute, Houston, US; 4 Erie Retina Research, Erie, US, 5 Retina Consultants Medical Group, Sacramento, US. Relevant Financial Disclosures: Funding: K23EY032990, R21EY034543, R01EY037916. Consultant: Kowa, Oculis, ANI Pharmaceuticals, AstraZeneca, AbbVie, Alfasigma, Kodiak Sciences, Genentech Edmund Tsui, MD Associate Professor of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles (UCLA), USA On behalf of the APEX Study Group

KSI-101 is a first-in-class, high-strength intravitreal biologic designed to target IL-6 mediated inflammation and VEGF-mediated vascular permeability simultaneously 2 KSI-101: high formulation strength (100 mg/mL)

Common Pathophysiology What is macular edema secondary to inflammation (MESI)? Blood Retinal Barrier Disruption Angiogenesis Inflammation 3 MESI is a heterogenous group of diseases that clinically present with macular edema and visual impairment, which are caused by a common pathophysiology: inflammation and blood retinal barrier disruption Macular edema with visual impairment Common Clinical Presentation Unifying Therapy? KSI-101

MESI comprises a heterogenous group of diseases with a common, readily identifiable clinical presentation: macular edema with visual impairment Anterior Intermediate Posterior Panuveitis Location of Inflammation Specific Etiology Idiopathic Juvenile Idiopathic Arthritis Focal Chorioretinal inflammation Punctate Inner Choroidopathy Post-Operative Macular Edema Irrespective of the anatomical location of the inflammation or the specific etiology, the clinical presentation is the same: macular edema 4

APEX study in the U.S.: multiple dose study of KSI-101 in patients with MESI Subjects with MESI (n=41) 5 Key inclusion criteria • Macular edema secondary to inflammation (MESI) • Diagnosis of active or inactive non-infectious intraocular inflammation, acute or chronic • Active leakage as evidenced by fluorescein angiogram • OCT CST of ≥320 microns • BCVA score ≤75 and ≥25 (20/32 to 20/320 Snellen equivalent) KSI-101 2.5 mg (n=13) KSI-101 5 mg (n=14) KSI-101 10 mg (n=14) All KSI-101 (N=41) Age, years, mean (SD) 74.2 (11.6) 67.4 (8.1) 67.5 (18.8) 69.6 (13.7) Female, n (%) 8 (61.5) 7 (50.0) 8 (57.1) 23 (56.1) Race, White, n (%) 11 (84.6) 11 (78.6) 14 (100) 36 (87.8) MESI disease duration, months , mean (SD) 12.2 (21.0) 1.7 (1.2) 15.8 (37.2) 11.1 (26.5) Inflammation anatomical location, n (%) Anterior 0 2 (14.3) 0 2 (4.9) Intermediate 1 (7.7) 0 2 (14.3) 3 (7.3) Posterior 10 (76.9) 6 (42.9) 10 (71.4) 26 (63.4) Panuveitis 2 (15.4) 6 (42.9) 2 (14.3) 10 (24.4) Patients with active inflammation, n (%) 3 (23.1) 11 (78.6) 5 (35.7) 19 (46.3) Unilateral MESI, n (%) 9 (69.2) 6 (42.9) 5 (35.7) 20 (48.8) BCVA, ETDRS Letters , mean (SD) 62.7 (7.4) 65.6 (7.9) 62.1 (8.4) 63.5 (7.9) Snellen equivalent ~20/50 ~20/50 ~20/63 ~20/50 OCT CST, μm , mean (SD) (Site reported ) 461.7 (137.7) 487.0 (124.1) 528.6 (157.3) 493.2 (139.7) OCT CST, μm , mean (SD) (Reading Center Data ) 451.3 (143.3) 488.7 (121.8) 517.7 (159.7) 486.8 (141.5) Lens Status, pseudophakic, n (%) 9 (69.2) 13 (92.9) 11 (78.6) 33 (80.5) Baseline Characteristics Study Design: Open-label Phase 1b in MESI Final results from the APEX Study in MESI. End of Study Weeks 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg KSI-101 intravitreal injection

60 65 70 75 80 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg 0 5 10 15 20 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg 2.5 mg 13 13 13 13 13 13 13 12 5 mg 13 13 13 13 13 13 13 13 10 mg 13 13 13 13 13 12 12 12 The top two dose levels achieve meaningful vision gains of >10 letters by Week 4 and continue to improve over time, achieving a 20/25 Snellen visual acuity 6 Mean ETDRS Letters Mean Change in BCVA over time Sample Size Observed BCVA over time Dose Level 2.5 mg 13 13 13 13 13 13 13 12 5 mg 13 13 13 13 13 13 13 13 10 mg 13 13 13 13 13 12 12 12 Sample Size Dose Level Mean ETDRS Letters +10.9 +13.4 +14.4 Weeks Weeks Final results of the APEX study in MESI. Includes patients in the per protocol set that completed the Week 4 visit and met all the eligibility criteria. Excludes one patient in the 5 mg dose that discontinued treatment before Week 4, and one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion). One patient in the 10 mg dose level discontinued after Week 12 due to recurrent uveitis flare-up Mean Change

More than half of patients achieved a ≥15 letter gain, with additional benefit observed in the top dose levels Proportion of ≥15 letter gainers Patients, % 38 62 54 51 0 20 40 60 80 100 2.5 mg (n=13) 5 mg (n=13) 10 mg (n=13) All patients (n=39) 7 Final results of the APEX study in MESI. Includes patients in the per protocol set that completed the Week 4 visit and met all the eligibility criteria. Excludes one patient in the 5 mg dose that discontinued treatment before Week 4, and one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion).

200 300 400 500 600 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg Final results of the APEX study in MESI. Includes patients in the per protocol set that completed the Week 4 visit and met all the eligibility criteria. Excludes one patient in the 5 mg dose that discontinued treatment before Week 4, and one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion). One patient in the 10 mg dose level discontinued after Week 12 due to recurrent uveitis flare-up. Meaningful anatomical improvements are rapidly achieved, with OCT CST levels <325 μm observed in the top two dose levels as early as Week 1, further deepening over time Mean CST (μm) Observed OCT CST over time Reading Center Data Dose Level Dryness (CST 250-325) 2.5 mg 13 12 13 13 13 13 13 12 5 mg 13 13 13 13 13 13 13 13 10 mg 13 13 13 13 13 12 12 12 Sample Size Mean Change -214 -226 -116 Weeks 8 Rapid improvement demonstrated within 1 week 1

8 77 85 96 96 96 92 80 0 20 40 60 80 100 0 1 4 8 12 16 20 24 Pooled 5 mg and 10 mg Patients, % Weeks 54 69 92 92 100 100 100 100 0 20 40 60 80 100 0 1 4 8 12 16 20 24 Patients, % Weeks Proportion of patients in the 5 and 10 mg (pooled) dose level achieving absence of IRF ≥90% of patients in the top two dose levels achieved absence of both intraretinal and subretinal fluid. A recurrence in IRF was observed in some patients 8 to 12 weeks after the last study treatment 26 26 26 26 26 25 25 25 Pooled 5 mg and 10 mg 26 26 26 26 26 25 25 25 Sample size Sample size Proportion of patients in the 5 and 10 mg (pooled) dose level achieving absence of SRF 9 Final results of the APEX study in MESI. Includes patients in the per protocol set that completed the Week 4 visit and met all the eligibility criteria. Excludes one patient in the 5 mg dose that discontinued treatment before Week 4, and one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion). One patient in the 10 mg dose level discontinued after Week 12 due to recurrent uveitis flare-up.

KSI-101 has been well-tolerated KSI-101 2.5 mg (n=13) KSI-101 5 mg (n=14) KSI-101 10 mg (n=14) All KSI-101 (N=41) Summary of AEs in the Study eye, n (%) Subjects with ≥1 AEs 2 (15.4) 3 (21.4) 2 (14.3) 7 (17.1) Treatment-related AEs 1 (7.7) a 1 (7.1) b 0 2 (4.9) Serious AEs 0 0 0 0 Treatment-related serious AEs 0 0 0 0 Severe AEs 0 0 0 0 AEs leading to study discontinuation 0 1 (7.1) b 0 1 (2.4) Selected AEs in the Study Eye, n (%) Intraocular inflammation (recurrent uveitis flare-up) 1 (7.7) a 1 (7.1) b 0 2 (4.9) Occlusive retinal vasculitis 0 0 0 0 Cataract 0 0 0 0 Elevated IOP 0 0 0 0 Eye Pain 1 (7.7) a 0 0 1 (2.4) Vitreous hemorrhage 1 (7.7) a 0 0 1 (2.4) Final results from the APEX Study in MESI. AE, Adverse event; IOP, intraocular pressure. Events are investigator reported. Adverse events are treatment-emergent events with start date ≥first study drug date and ≤last study drug date + 28 days. a Same patient. Vitreous hemorrhage secondary to aqueous humor sampling at the Day 1 visit (pre-dose). The patient had 3+ AC cells and flare and 2+ vitreous haze prior to the Day 1 KSI-101 dose. The patient safely received all 4 doses of KSI-101 and is +26 letters in BCVA at their last visit and no intraocular inflammation. b Same patient. Uveitis flare-up consistent with underlying disease. 10

Single-dose KSI-101 demonstrates rapid, meaningful responses in MESI, independent of inflammation location or macular edema etiology Location of Inflammation Specific Macular Edema Etiology Idiopathic Juvenile Idiopathic Arthritis Focal Chorioretinal inflammation Punctate Inner Choroidopathy Post-Operative Macular Edema Day 1 Anterior Intermediate Posterior Panuveitis Day 1 Week 4 Effect of a single dose of KSI-101 Week 4 11

KSI-101 achieves dryness and normalizes the retinal architecture in the majority of patients 1 2 3 4 5 6 7 8 9 10 12 11 13 KSI-101 2.5 mg 14 15 16 17 18 19 20 21 22 24 23 25 26 KSI-101 5 mg 27 28 29 30 31 32 33 34 35 36 37 38 39 KSI-101 10 mg Week 12 visit shown above. Subject ET at W12. No data available for W16 or W24 Subject Day 1 Week 16 Week 24 12 weeks since last injection Post-loading Subject Day 1 Week 16 Week 24 12 weeks since last injection Post-loading Subject Day 1 Week 16 Week 24 12 weeks since last injection Post-loading Reactivation at W20 Received rescue therapy (W24 data censored) 12

Clinical results of KSI-101 in MESI from tertiary uveitis centers in Asia

Multiple dose clinical PK/PD cohort in Asian patients with MESI End of Study Subjects with MESI (n=13) Weeks 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg 14 KSI-101 intravitreal injection Key inclusion criteria • Macular edema secondary to inflammation (MESI) • Diagnosis of active or inactive non-infectious intraocular inflammation, acute or chronic • Active leakage as evidenced by fluorescein angiogram • OCT CST of ≥320 microns • BCVA score ≤75 and ≥25 (20/32 to 20/320 Snellen equivalent) Baseline Characteristics • Pharmacokinetics, tolerability and clinical activity of KSI-101 was evaluated in a clinical cohort of Asian patients at tertiary uveitis centers in Taiwan Study Design: Open-label Phase 1b in MESI APEX U.S. Asia KSI-101 2.5 mg (n=13) KSI-101 5 mg (n=14) KSI-101 10 mg (n=14) KSI-101 pooled (N=13) Age, years, mean (SD) 74.2 (11.6) 67.4 (8.1) 67.5 (18.8) 49.9 ( 22.6) Female, n (%) 8 (61.5) 7 (50.0) 8 (57.1) 11 (84.6) Race, Asian, n (%) 0 1 (7.1%) 0 13 (100) Race, White, n (%) 11 (84.6) 11 (78.6) 14 (100) 0 MESI disease duration, months , mean (SD) 12.2 (21.0) 1.7 (1.2) 15.8 (37.2) 2.3 ( 1.9) Inflammation anatomical location, n (%) Anterior 0 2 (14.3) 0 1 (7.7) Intermediate 1 (7.7) 0 2 (14.3) 2 (15.4) Posterior 10 (76.9) 6 (42.9) 10 (71.4) 6 (46.2) Panuveitis 2 (15.4) 6 (42.9) 2 (14.3) 5 (38.5) Patients with active inflammation, n (%) 3 (23.1) 11 (78.6) 5 (35.7) 12 (92.3) Unilateral MESI, n (%) 9 (69.2) 6 (42.9) 5 (35.7) 4 (30.8) BCVA, ETDRS Letters , mean (SD) 62.7 (7.4) 65.6 (7.9) 62.1 (8.4) 58.5 (14.1) Snellen equivalent ~20/50 ~20/50 ~20/63 ~20/63 OCT CST, μm , mean (SD) (Site reported) 461.7 (137.7) 487.0 (124.1) 528.6 (157.3) 429.8 (76.3) Lens Status, pseudophakic, n (%) 9 (69.2) 13 (92.9) 11 (78.6) 7 (53.8)

Meaningful vision gains of >10 letters were observed after a single injection in the Asian cohort, with continued improvement through 24 weeks 15 Final results of the APEX study in MESI. Includes patients in the per protocol set that completed the Week 4 visit and met all the eligibility criteria. US: Excludes one patient in the 5 mg dose that discontinued treatment before Week 4, and one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion). One patient in the 10 mg dose level discontinued after Week 12 due to recurrent uveitis flare-up. Asian cohort: excludes one patient with a significant epiretinal membrane at baseline (exclusion criterion). One patient discontinued after Week 12 due to a spinal fracture. 0 5 10 15 20 0 4 8 12 16 20 24 Mean ETDRS letters Weeks U.S. 2.5 mg U.S. 5 mg U.S. 10 mg Asia Pooled 2.5 mg 13 13 13 13 13 13 13 12 5 mg 13 13 13 13 13 13 13 13 10 mg 13 13 13 13 13 12 12 12 Pooled 12 12 12 12 12 11 11 11 U.S. Asia Mean Change in BCVA Sample Size

More than half of patients achieved a ≥15 letter gain, consistent with the findings from the APEX study in the U.S. 16 Proportion of ≥15 letter gainers Patients , % 38 62 54 58 0 20 40 60 80 100 U.S. 2.5 mg (n=13) U.S. 5 mg (n=13) U.S. 10 mg (n=13) Asia Pooled (n=12) U.S. Asian Cohort Final results of the APEX study in MESI. Includes patients in the per protocol set that completed the Week 4 visit and met all the eligibility criteria. US: Excludes one patient in the 5 mg dose that discontinued treatment before Week 4, and one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion). Asian cohort: excludes one patient with a significant epiretinal membrane at baseline (exclusion criterion).

U.S. Asia KSI-101 consistently achieved dryness (CST 250 - 325 μm) after a single injection, with sustained dryness observed during follow-up 17 200 300 400 500 600 0 4 8 12 16 20 24 Mean CST (μm) Weeks U.S. 2.5 mg U.S. 5 mg U.S. 10 mg Asia Pooled 2.5 mg 13 12 13 13 13 13 13 12 5 mg 13 13 13 13 13 13 13 13 10 mg 13 13 13 13 13 12 12 12 Pooled 12 12 12 12 12 11 11 11 Dryness (CST 250 – 325) Final results of the APEX study in MESI. Includes patients in the per protocol set that completed the Week 4 visit and met all the eligibility criteria. US: Excludes one patient in the 5 mg dose that discontinued treatment before Week 4, and one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion). One patient in the 10 mg dose level discontinued after Week 12 due to recurrent uveitis flare-up. Asian cohort: excludes one patient with a significant epiretinal membrane at baseline (exclusion criterion). One patient discontinued after Week 12 due to a spinal fracture. Results are site reported CST values. Observed OCT CST Sample Size Rapid improvement demonstrated within 1 week 1

KSI-101 has been well-tolerated 18 Asia KSI-101 pooled (N=13) Summary of AEs in the Study eye, n (%) Subjects with ≥1 AEs 3 (23.1) Treatment-related AEs 0 Serious AEs 0 Treatment-related serious AEs 0 Severe AEs 0 AEs leading to study discontinuation 0 Selected AEs in the Study Eye, n (%) Intraocular inflammation 0 Occlusive retinal vasculitis 0 Cataract 0 Dry Eye 1 (7.7) Ocular discomfort 1 (7.7) Posterior capsule opacification 1 (7.7) AE, Adverse event. Events are investigator reported. Adverse events are treatment-emergent events with start date ≥first study drug date and ≤last study drug date + 28 days. KSI-101 was safe and well tolerated. No cases of retinal vasculitis or occlusive retinal vasculitis were observed.

Based on positive APEX data, the 5 mg and 10 mg dose levels have advanced into the Phase 3 PEAK and PINNACLE studies in MESI • KSI-101 in MESI patients consistently showed robust anatomic and visual responses in the Apex study conducted in the U.S. and in the clinical cohort from tertiary uveitis centers in Asia ‒ Over half of patients achieved at least a ≥15 letter gain ‒ Dryness was achieved after a single injection with sustained dryness observed during follow-up ‒ Consistent responses were observed irrespective of different underlying etiologies • PEAK and PINNACLE Phase 3 studies in MESI are actively enrolling 19 PEAK: NCT06990399. PINNACLE: NCT06996080 Key inclusion criteria • Macular edema secondary to inflammation • Diagnosis of active or inactive non-infectious intraocular inflammation, acute or chronic • Active leakage as evidenced by fluorescein angiogram • OCT CST of ≥320 microns • BCVA score ≤78 and ≥25 (~20/25 to 20/320 Snellen) Mean change in BCVA from Day 1 to the average of Week 20 and Week 24