The Retina Society 58th Annual Scientific Meeting

Bispecific trap-antibody inhibiting interleukin-6 and vascular endothelial growth factor (KSI-101): first-time results from the Phase 1b APEX Study in patients with macular edema secondary to inflammation (MESI) Dolly Chang 1 ; Allen Hu 2 ; David Almeida 3 ; Scott Fitzpatrick 1 ; Victor Perlroth 1 ; J. Pablo Velazquez-Martin 1 1 Kodiak Sciences, Palo Alto, United States, 2 Cumberland Valley Retina Consultants, Hagerstown, United States, 3 Erie Retina Research, Erie, United States Relevant Financial Disclosures: Research with and Consultant for Kodiak Dr. Chang, Dr. Fitzpatrick, Dr. Perlroth and Dr. Velazquez-Martin are employees of Kodiak Sciences Charles C. Wykoff, M.D., Ph.D. Deputy Chair of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital Director of Research, Retina Consultants of Texas; Retina Consultants of America on behalf of the APEX Study Group

Dysregulation of the immune system causes a series of insults to the blood-ocular barrier, leading to breakdown of the barrier and release of inflammatory mediators Inflammatory insults (e.g., autoimmune diseases) can disrupt the blood-retinal barrier Yang et al. Int. J. Mol. Sci. 2023, 24: 4676. Metcalfe et al. Front. Immunol. 2020, 11: 1424. Shaik et al. Biomolecules. 2020, 10: 1673. Valle et al. Exp Eye Res. 2019, 178: 27. Mesquida et al. Trans Vis Sci Tech. 2019, 8: 32. Blood-retinal barrier breakdown allows immune cells and blood plasma into the retina, causing inflammation, leakage and macular edema IL-6 and VEGF are co-induced: IL-6 sustains inflammation and upregulates VEGF, which promotes vascular leak and neovascularization. Together, IL-6 and VEGF compound damage to the blood-retinal barrier 1 2 3 Blood-retinal barrier breakdown Normal

CME: cystoid macular edema 1. Adapted from Valentincic et al. Molecular Vision 2011; 17: 2003-2010. 2. Adapted from Fine et al. Am J Ophthal. 2001; 132: 794-796. Aqueous humor IL-6 levels in patients with intermediate uveitis 1 VEGF levels in aqueous humor of uveitis patients with macular edema vs without macular edema 2 2 • IL-6 levels are elevated in patients with ocular inflammation and further elevated in patients with inflammatory macular edema • Persistent inflammation triggers VEGF upregulation. VEGF levels are found to be elevated in eyes with inflammatory macular edema VEGF IL-6 Both IL-6 and VEGF are implicated in the pathogenesis of inflammatory macular edema

KSI-101 is a first-in-class, high-strength intravitreal biologic designed to target IL-6 mediated inflammation and VEGF-mediated vascular permeability simultaneously VEGF IL-6 IL-6 KSI-101: high formulation strength (100 mg/mL) 3

0 20 40 60 0 50 100 150 Hours % Resistance No Exposure VEGF + IL-6/R VEGF + IL-6/R + anti-VEGF VEGF + IL-6/R + KSI-101 VEGF + IL-6/R + anti-IL-6 Bispecific KSI-101 restores barrier resistance from pre-existing insult greater than anti-IL-6 or anti-VEGF monotherapies alone Exposure Start (Exogenous VEGF and IL-6) Treatment High barrier resistance Intact tight junctions KSI-101 restores barrier integrity to no exposure levels Anti-VEGF and anti-IL- 6 monotherapy only partially restore barrier function No Exposure VEGF + IL-6/R + KSI-101 VEGF + IL-6/R + anti-VEGF VEGF + IL-6/R + anti-IL-6 VEGF + IL-6/R HUVEC cells were treated as indicated after growth to establish barrier 4 VEGF + IL6 disrupt the barrier integrity synergistically Preclinical model of endothelial cells simulating the blood-retinal barrier

What is macular edema secondary to inflammation (MESI)? Macular Edema with visual impairment Blood Retinal Barrier Disruption VEGF IL-6 IL-6 KSI-101 Common Clinical Presentation Common Pathophysiology Potential common therapy Angiogenesis Inflammation 5 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

Anterior Intermediate Posterior Panuveitis Location of inflammation MESI comprises a heterogenous group of diseases with a common, readily identifiable clinical presentation: macular edema with visual impairment 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 6

Phase 1b APEX study: multiple dose study of KSI-101 in patients with MESI End of Study Subjects with MESI (n=41) Weeks 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg 7 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) Enrollment complete 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 (20.1) 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) 10 (71.4) 5 (35.7) 18 (43.9) Unilateral MESI, n (%) 9 (69.2) 6 (42.9) 5 (35.7) 20 (48.8) BCVA, ETDRS Letters , mean (SD) 62.7 (7.4) 65.5 (7.8) 62.1 (8.4) 63.5 (7.8) Snellen equivalent ~20/50 ~20/50 ~20/63 ~20/50 OCT CST, μm , mean (SD) 461.7 (137.7) 487.0 (124.1) 528.6 (157.3) 493.2 (139.7) Lens Status, pseudophakic, n (%) 9 (69.2) 13 (92.9) 11 (78.6) 33 (80.5) Baseline Characteristics Study Design: Ongoing, Open-label Phase 1b in MESI The APEX study is ongoing. Final results may be different due to data cleaning.

60 65 70 75 80 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg APEX KSI-101 in MESI – Meaningful vision gains are rapidly achieved as early as Week 4 and ≥half of patients in the top two dose levels achieved a ≥15 letter gain 8 The APEX study is ongoing. Final results may be different due to data cleaning. Includes patients in the per protocol set that completed the Week 12 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). Mean ETDRS Letters Observed BCVA over time Sample Size Weeks 2.5 mg 13 13 13 13 13 5 mg 13 13 13 13 13 10 mg 13 13 13 13 13 Proportion of ≥15 letter gainers Patients, % +10.7 +12.1 +8.8 31 62 54 49 0 20 40 60 80 100 2.5 mg (n=13) 5 mg (n=13) 10 mg (n=13) All patients (n=39) Mean Change Dose Level Preliminary analysis: all patients have completed Week 12

200 300 400 500 600 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg 8 74 79 92 100 0 20 40 60 80 100 0 1 4 8 12 16 20 24 38 38 33 25 21 N values Pooled KSI-101 Patients, % Weeks 55 68 91 92 100 0 20 40 60 80 100 0 1 4 8 12 16 20 24 Patients, % Weeks Proportion of patients achieving absence of IRF b Proportion of patients achieving absence of SRF b The APEX study is ongoing. Final results may be different due to additional data collection or data cleaning. a Includes patients in the per protocol set that completed the Week 12 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). b Includes patients in the per protocol set that meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion). Includes all data available by the 14-Jul-25 reporting date. 9 38 38 33 25 21 N values Pooled KSI-101 APEX KSI-101 in MESI – A single dose of KSI-101 results in the majority of patients achieving dryness. Over 90% of patients achieve dryness by Week 8 Mean CST (μm) Observed OCT CST over time a Weeks 2.5 mg 13 13 13 13 13 5 mg 13 13 13 13 13 10 mg 13 13 13 13 13 Dryness (CST <325) -216 -240 -165 Sample Size Mean Change Dose Level

APEX KSI-101 in MESI – KSI-101 was 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) The APEX study is ongoing. Final results may be different due to additional data collection or data cleaning. 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

Location of inflammation Anterior Intermediate Posterior Panuveitis Day 1 Week 4 Effect of a single dose of KSI-101 After a single dose of KSI-101, heterogenous MESI diseases show rapid and meaningful responses to the simultaneous IL-6 and VEGF inhibition, irrespective of the location of the inflammation or the specific macular edema diagnosis Specific Macular Edema Etiology Idiopathic Juvenile Idiopathic Arthritis Focal Chorioretinal inflammation Punctate Inner Choroidopathy Post-Operative Macular Edema Day 1 Week 4 Effect of a single dose of KSI-101 11

55 60 65 70 75 80 85 90 200 300 400 500 600 0 4 8 12 16 20 24 APEX KSI-101 in DME – Meaningful visual and anatomical gains were achieved with KSI-101, with additional benefits with continued dosing. KSI-101 was well-tolerated N values All KSI-101 12 12 12 11 11 11 11 11 Mean OCT CST (microns) Mean Change in BCVA and OCT CST in DME All KSI-101 dose levels combined End of Study Subjects with DME (n=12) Weeks 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg KSI-101 intravitreal injection Study Design: Ongoing, Open-label Phase 1b in treatment-naïve DME All KSI-101 (N=12) Summary of AEs in the Study eye, n (%) Subjects with ≥1 AEs 1 (8.3) Treatment-related AEs 0 Serious AEs 0 Treatment-related serious AEs 0 Severe AEs 0 AEs leading to study discontinuation 0 AEs in the Study Eye, n (%) Intraocular inflammation 0 Occlusive retinal vasculitis 0 Cataract 0 Cataract traumatic* 1 (8.3) The APEX study is ongoing. Final results may be different due to additional data collection or data cleaning. 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. * Anterior traumatic cataract due to aqueous humor routine sample Safety Weeks Letters: +12.0 Dryness (CST <325) Microns: -157 Mean BCVA (letters) 12

Conclusions : KSI-101 demonstrated meaningful visual and anatomical improvements in patients with MESI in the APEX Study • MESI: group of diseases with a shared pathophysiology — inflammation & BRB disruption • Treatment with KSI-101 in MESI patients in APEX, 12-week analyses: ‒ Robust anatomic and visual responses to date ‒ Half of patients achieved a ≥15 letter gain. ‒ >90% resolution of both IRF & SRF by Week 8 ‒ Consistent response with different underlying etiologies • Two Phase 3 trials of KSI-101 in MESI actively enrolling PEAK Moderate to severe edema with moderate to severe vision impairment Mild edema with any vision impairment Moderate to severe edema with good vision PINNACLE PEAK: NCT06990399. PINNACLE: NCT06996080 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 ≤78 and ≥25 (~20/25 to 20/320 Snellen) VEGF IL-6 IL-6 KSI-101 PEAK and PINNACLE are actively enrolling 13