Slides
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INVESTOR R&D DAY
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WELCOME & INTRODUCTIONS 2
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3 Forward-Looking Statements These slides contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding: the progress and anticipated benefits of our ABC platform; the prospects and anticipated milestones of the candidates in our pipeline, including tarcocimab, KSl-501, and KSl-101; the timing and success of our planned Biologics License Application ("BLA") package; the timing of anticipated topline data readouts; the potential to provide sustainable revenue streams starting from 2027; the net sales potential of our clinical portfolio; and the addressable population of KSI-101. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "could," "expect," "plan," "believe," "intend," "pursue," and other similar expressions among others. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. The risks and uncertainties include, but are not limited to: the risk that cessation or delay of any of the on-going clinical studies and our development of tarcocimab, KSl-501 or KSl-101 may occur; the risk that ongoing clinical trial results may not provide the evidence, insights, or benefits as anticipated; the risk that safety, efficacy, and durability data observed in our product candidates in current or prior studies may not continue or persist; the risk that the results of the tarcocimab Phase 3 studies may not be sufficient to support a single BLA submission for DR, RVO and wet AMD; the risk that a BLA may not be accepted by, or receive approval from, the FDA or foreign regulatory agencies when expected, or at all; future potential regulatory milestones of tarcocimab, KSl-501 or KSl-101, including those related to current and planned clinical studies, may be insufficient to support regulatory submissions or approval; the risk that a new formulation of tarcocimab, KSl-501 or other ABC Platform derived molecules may not provide the benefits expected; our research and development efforts and our ability to advance our product candidates into later stages of development may fail; the risk that KSl-501 may not inhibit VEGF and IL-6 or have an impact on the treatment of patients as expected; any one or more of our product candidates may not be successfully developed, approved or commercialized; our manufacturing facilities may not operate as expected; adverse conditions in the general domestic and global economic markets, which may significantly impact our business and operations, including our clinical trial sites, as well as the business or operations of our manufacturers, contract research organizations or other third parties with whom we conduct business; as well as the other risks identified in our filings with the Securities and Exchange Commission. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10- Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and Kodiak undertakes no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. Kodiak®, Kodiak Sciences®, ABC , ABC Platform , and the Kodiak logo are registered trademarks or trademarks of Kodiak Sciences Inc. in various global jurisdictions.
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5 Today’s Attendees Victor Perlroth, MD Chairman and CEO Pablo Velazquez-Martin, MD Chief Medical Officer Dolly S. Chang, MD, PhD Chief Scientific Officer John Borgeson Chief Financial Officer Presenters from Kodiak Management Industry Experts Charles Wykoff, MD, PhD • Director of Research, Retina Consultants of Texas • Chairman of Research, Retina Consultants of America • Professor of Clinical Ophthalmology and Deputy Chair of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital Sumit Sharma, MD • Enterprise Vice Chair, Integrated Surgical Institute • Medical Director, Information Technology – Ophthalmology • Vitreoretinal Surgery and Uveitis/Ocular Inflammatory Diseases, Cole Eye Institute, Cleveland Clinic 5
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6 Guest Speakers and Industry Experts Charles Wykoff, MD, PhD Director of Research, Retina Consultants of Texas Chairman of Research, Retina Consultants of America Professor of Clinical Ophthalmology and Deputy Chair of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital • Medical and surgical retina specialist and an active clinical investigator for exudative and atrophic retinal diseases • Major themes in his research are a translational focus, utilizing novel biomarkers and accelerating drug and device development • 350+ publications and serves on multiple scientific and medical advisory boards, safety monitoring committees, and global steering committees for endeavors spanning the innovative process from early to late-stage developments • A member of the NEI Audacious Goals Steering Committee and has been awarded multiple Achievement, Honor and Senior Honor Awards • His guiding philosophy is to build and strengthen innovative, ethical teams focused on developing new approaches to improving outcomes for blinding diseases. 6
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7 Guest Speakers and Industry Experts • Vitreoretinal Surgeon and Uveitis Specialist at Cole Eye Institute, Cleveland Clinic with a special interest in clinical trials and advanced imaging analysis • Keen interest in designing new imaging based quantitative outcome metrics for both clinical practice and clinical trials in AMD, DME, RVO and uveitis • Actively involved in clinical trials serving as the principal or co-investigator of over 80 clinical trials in all phases of development • 100+ peer reviewed publications including as the first author of multiple clinical trials • Serves as the Enterprise Vice Chair for Clinical Outcomes, Safety, Quality and Patient Experience for the Integrated Surgical Institute, including 7 surgical departments at Cleveland Clinic with oversight over all Cleveland Clinic locations in Ohio, Florida, London and Abu Dhabi Sumit Sharma, MD Enterprise Vice Chair, Integrated Surgical Institute Medical Director, Information Technology – Ophthalmology Vitreoretinal Surgery and Uveitis/Ocular Inflammatory Diseases, Cole Eye Institute, Cleveland Clinic 7
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Welcome, Safe Harbor, Agenda John Borgeson, Chief Financial Officer Victor Perlroth, M.D., Chief Executive Officer Key Messages, What to Expect Today Victor Perlroth, MD Chief Executive Officer Tarcocimab and KSI-501: Retinal Vascular Diseases Charles Wykoff, MD, PhD KSI-101: Macular Edema Secondary to Inflammation Summary, Q&A, Closing Kodiak Management Team and Industry Leaders Sumit Sharma, MD Commercial opportunity Victor Perlroth, MD Chief Executive Officer What is MESI? What causes MESI? What is the unmet need? How can this unmet need be addressed? Phase 1b APEX Study – DME and MESI cohorts How does KSI-101 fit into the emerging treatment landscape? PEAK and PINNACLE: KSI-101 pivotal program Charles Wykoff, MD, PhD A patient’s MESI journey Dolly S. Chang, MD, PhD Chief Scientific Officer 8
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9 Victor Perlroth, MD Chairman and CEO Key Messages & What to Expect
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• Strong 12-week data from Phase 1b APEX • PEAK and PINNACLE – already enrolling • Commercial opportunity of 150,000+ initial addressable patients with headroom • Science-based “heavyweights”? • Tarcocimab: targeting BLA mid-2026 in wet AMD, RVO and diabetic retinopathy • KSI-501: bispecific ABC® may be even better! • KSI-102, KSI-103: bispecifics for inflammation • Duets for glaucoma and geographic atrophy • VETi: AI headsets for commercial leadership • URSUS: commercial manufacturing A potent reason to believe in Kodiak 2 options in the $15+ billion anti-VEGF market Accelerating our technology and product leadership in retina KSI-101 Tarcocimab & KSI-501 Pipeline, Digital Health, Manufacturing Wholly Owned Kodiak Investor R&D Day July 2025 – Key Messages 10 . AMD: age-related macular degeneration; RVO: retinal vein occlusion; ABC: antibody biopolymer conjugate
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3 late-stage assets, in 4 Phase 3 studies, with topline data expected across 2026 Mainstay biologic with science of immediacy and durability, on track for BLA filing in 2026 in 3 indications of wet AMD, DR and RVO Tarcocimab Anti-VEGF ABC® Mainstay biologic with potential for additional efficacy beyond anti-VEGF monotherapies while maintaining immediacy and signature durability of ABC platform KSI-501 Anti-IL-6, VEGF trap bispecific ABC® High-strength, dual inhibition of IL-6 and VEGF, for safe and potent control of macular edema secondary to inflammation (MESI) KSI-101 High-strength anti-IL-6, VEGF trap bispecific protein . ABC: antibody biopolymer conjugate; DR: diabetic retinopathy; RVO: retinal vein occlusion; AMD: age-related macular degeneration Quadrant of core unmet need Quadrant of core unmet need Greenfield market opportunity For patients with retinal vascular diseases For patients with MESI 11
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MOA Indication Phase 3 Study Complete Q1 ‘26 Q2 ‘26 Q3 ‘26 Q4 ‘26 1Q ’27 2Q ’27 3Q ‘27 Tarcocimab Anti-VEGF Antibody Biopolymer Conjugate (ABC) RVO BEACON BLA* DR GLOW1 Wet AMD DAYLIGHT DR GLOW2 Wet AMD DAYBREAK KSI-501 Anti-IL-6, VEGF Trap ABC Wet AMD DAYBREAK Wet AMD 2nd Pivotal KSI-101 Anti-IL-6, VEGF Trap Protein MESI PEAK PINNACLE Kodiak is a precommercial retina biotech with a portfolio of three Phase 3 assets, with BLA facing data expected across 2026, and a series of BLA filings possible in 2026 and then 2027 ABC: antibody biopolymer conjugate; DR: diabetic retinopathy; AMD: age-related macular edema; RVO: retinal vein occlusion; MESI: macular edema secondary to inflammation; BLA: biologics license application; GLOW2: NCT06270836. DAYBREAK: NCT06556368 * Based on expected timeline of clinical data = BLA-facing topline data readouts (expected) BLA* BLA* 12
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Kodiak’s pipeline has the potential to provide sustainable revenue streams starting from 2027, with built-in life cycle management, risk diversification and continuing technology and product leadership in retina Net sales (USD) 2027 2028 2029 2030 2031 2032 Tarcocimab KSI-501 KSI-101 Net Sales Potential of Kodiak Clinical Portfolio (Illustrative) Tarcocimab launch in DR, wet AMD and RVO Potential launch of KSI-501 Potential launch of KSI-101 in MESI With potential for strong immediacy and best durability Mainstay Biologic With potential for best efficacy AND strong immediacy and best durability “Next gen” product to fast follow tarcocimab Mainstay Biologic Greenfield market Safe, potent, local biologic in a greenfield market segment of high unmet needKodiak’s assets are proprietary and wholly-owned. We have the flexibility in our commercialization decisions to support adoption of our products in the marketplace. 13
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14 Tarcocimab & KSI-501 Charles Wykoff MD, PhD
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The Retinal Vascular Diseases and the Anti-VEGF Market: Tarcocimab & KSI-501 15
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There remains valuable open space in the retinal vascular diseases market, despite the availability of approved biologics and clinical trials of new exploratory technologies Efficacy Durability Gen 1.0 • Eylea • Lucentis • Biosimilars Gen 1.5 • Eylea HD • Vabysmo Implants Gene Therapies Approved mainstay biologics that provide: High Immediacy High Immediacy + Incremental Durability Exploratory technology-products in clinical trials designed for: High Durability High Immediacy + High Durability At the same time and in the same product A biologic that provides: 16
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The Gen 1.0 biologics that provide immediacy and the Gen 1.5 biologics that provide immediacy and incremental durability are meaningful for patients and physicians Gen 1.0 Good efficacy, limited durability Gen 1.5 Immediacy Incremental durability Q4W Q8W Q12W Q16W Wet AMD DME DR RVO Wet AMD DME DR RVO Wet AMD DME RVO Wet AMD DME DR Dosing regimen per label for approved intravitreal biologics RVO Q8W dosing pending FDA approval Q20W Q24W $1.2B in 2024 $8.2B in 2024 $4.4B in 2024 $1.2B in 2024 This sustained commercial success is a testament to: • The power of the intravitreal biologic as the mainstay of therapy • The unmet need that remains for patients 17
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Despite their commercial success, real-world data in wet AMD show that most patients are falling short of the durability promise of the Gen 1.5 labels 181. Adapted from Durga Borkar, et al. Poster presented at ARVO 2025. Poster #3108. Treatment-Naïve Eyes (n=389a) Previously Treated Eyes (n=6364a) Faricimab injections observed after the first 6 months of treatment through Year 2 in the FARENTINA study2 Year 2: ~4.5 Year 2: ~6 Most patients are on a Q8W- Q12W schedule in the real world in Year 2 a Only eyes with ≥ 1 injection after index and prior to censoring were included. In Year 2, patients received 4.5 injections which is an average dosing interval of every 11.5 weeks In Year 2, patients received 6.0 injections which is an average dosing interval of every 8 weeks
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Technologies being explored in clinical trials, including implants and gene therapies, are engineering for high durability but are lacking immediacy Maintenance agents to be used in subset of patients but always relying on mainstay biologics to (re)establish disease control • Engineering for durability • Long-term safety unknown Implants • Engineering for durability • Onerous monitoring and inflammation control • Long-term safety unknown Gene Therapies Implants and gene therapies are being tested on top of mainstay biologics, which are given during the loading phase and then as needed during the maintenance phase. 19
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Therefore, the open space remains. A biologic that provides high immediacy and high durability at the same time and in the same therapy has the potential to be a heavy weight in this important $15+ billion marketplace Mainstay intravitreal biologic monotherapies for all patients Gen 1.0 • Eylea • Lucentis • Biosimilars Gen 1.5 • Eylea HD • Vabysmo Onerous monitoring and inflammation control. Long-term safety unknown Maintenance agents to be used in subset of patients but always relying on mainstay biologics to (re)establish disease control Implants Gene Therapies Efficacy Durability High Immediacy + High Durability At the same time and in the same product A biologic that provides: 20
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Kodiak’s ABC® Platform Science in Retina 21
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The ABC® Platform supports Kodiak’s SCIENCE OF IMMEDIACY and DURABILITY Designed-in Extended Tissue Residence Time A proprietary phosphorylcholine- based polymer is conjugated to an antibody to increase molecular size which extends ocular half-life High in-Vitro Potency Extended Ocular Half-Life in Animals Extended Ocular Half- Life in Humans Powerful Immediacy via Unconjugated Antibody Both unconjugated protein and conjugated protein demonstrate high binding affinity and potency in vitro 3x the ocular t½ of approved intravitreal biologics when measured in rabbits following an intravitreal injection 3x the ocular t½ of faricimab when measured from aqueous humor in patients following an intravitreal injection The unconjugated protein delivers a strong “pulse” of anti-VEGF inhibition during the loading phase, or to recapture control of the disease in patients whose disease has reactivated Extended Clinical Durability via Conjugated Antibody The conjugated protein maintains the signature durability as seen in Kodiak’s pivotal studies to date 22
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Tarcocimab and KSI-501 bring the best of both worlds – with a science of high immediacy and high durability at the same time in a single biologic Molecular Size (kDa) 149 kDa 210 kDa 950 kDa 1000 kDa 149 kDa Immediacy is achieved with lower molecular weight intravitreal biologics Durability increases as molecular weight increases for intravitreal biologics 23
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Tarcocimab and KSI-501 bring the best of both worlds – with a science of high immediacy and high durability at the same time in a single biologic Molecular Size (kDa) Tarcocimab KSI-501 + 1 mg unconjugated protein for immediacy 4 mg high molecular weight ABC® for durability + 1.5 mg unconjugated protein for immediacy 3.5 mg high molecular weight ABC® for durability 24
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Tarcocimab has a mean ocular half-life in humans of 20 days, which is 3-fold longer than faricimab Human Ocular Half-Life (Days) 10-90th percentiles 8.3 (10th percentile) 31.8 (90th percentile) 19.8 days (Mean) 5.2 (10th percentile) 11.2 (90th percentile) 7.5 days (Mean) t½ <5 days t½ >11 days Faricimab Tarcocimab Percent of Patients Each dot represents the ocular half-life from one individual patient. Blue dots are tarcocimab from the Phase 1b study of tarcocimab in patients with wet AMD, DME and RVO. Gray dots are faricimab from Genentech, Inc. PK and ER of faricimab, Report # 1105763 0% 81% 10% 10% 0 20 40 60 80 100 FARICIMAB TARCOCIMAB 25
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Tarcocimab demonstrated consistent 20-day ocular half-life across wet AMD, DME and RVO patients All Wet AMD DME RVO 0 10 20 30 40 50 n=47 n=23 DME n=8 n=16 Tarcocimab Human Ocular Half-Life by Indication RVO n=16 wAMD n=23 All n=47 Height of the box represents the mean; error bars represent standard deviation. Aqueous Humor t 1/2 (days) 26
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From 4 to 10 days From 7 to 18 days From 12 to 28 days Modeling suggests tarcocimab may provide a similar immediacy of efficacy while meaningfully extending dosing intervals for all patient types 1 10 100 1000 10000 0 30 60 Ocular Drug Quantity Time (days) Patient with Short Ocular T1/2 0 30 60 90 120 150 Time (days) Patient with Average Ocular T1/2 0 30 60 90 120 150 180 210 240 Time (days) Patient with Long Ocular T 1/2 Faricimab Tarcocimab Conjugated ProteinTarcocimab Unconjugated Protein Tarcocimab extends dosing interval from 3-4 weeks to 6-8 weeks Tarcocimab extends dosing interval from 8 weeks to 3+ months Tarcocimab extends dosing interval from 12 weeks to 6+ months Faricimab & Tarcocimab free protein t1/2 = 7 days Tarcocimab conjugate t1/2 =18 days Tarcocimab conjugate t1/2 =10 days Faricimab & Tarcocimab free protein t1/2 = 4 days TARCOCIMAB Extended T1/2 FARICIMAB VABYSMO (faricimab solution for injection) Prescribing Information. South SanFrancisco, USA: Genentech, Inc. PK and ER of Faricimab, Report # 1105763 10-90th percentiles Faricimab & Tarcocimab free protein t1/2 = 12 days Tarcocimab conjugate t1/2 =28 days Human Ocular Half-Life (Days) 27
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ABC® Enabled Mainstay Biologics • Strong Immediacy • Industry-leading Durability • Better Efficacy • Strong Immediacy • Industry-leading Durability Tarcocimab KSI-501 28
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Kodiak’s ongoing and planned clinical studies have a high probability of success to support a tarcocimab BLA in 2026 and a potential KSI-501 BLA in 2027 while supporting complementary and potentially differentiated commercial profiles Indication Phase 3 Study Primary Endpoint 6-Month Durability Results / Progress Tarcocimab RVO BEACON • Doubled treatment interval (Q8W) at PE (month 6) and ~50% of tarcocimab treated patients on 6-month dosing at Year 1 DR GLOW1 • 100% of patients on 6-month dosing at Year 1 Wet AMD DAYLIGHT Not Applicable • Monthly study of tarcocimab demonstrated favorable safety and non-inferior efficacy at Year 1 DR GLOW2 Superiority • Topline data on track for 1Q 2026 • Design mirrors successful GLOW1 study Wet AMD DAYBREAK Non- Inferiority • Expecting to close screening end of August • Topline data expected mid 2026 KSI-501 Wet AMD DAYBREAK Non- Inferiority Not Applicable • Expecting to close screening end of August • Topline data expected mid 2026 Wet AMD 2nd Pivotal TBD TBD • In planning • Exploring start in 4Q 2025 / 1Q 2026 • Targeting BLA mid-2027 CompletedOngoingOngoingPlanned 29
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Tarcocimab and KSI-501 in wet AMD: DAYBREAK study explores in a definitive manner immediacy through the loading phase and real-world durability and, in the case of KSI-501, the potential for better efficacy DAYBREAK study design: a registrational study for both tarcocimab and KSI-501 DAYBREAK uses an AI-based tool to precisely measure fluid in the eye so that treatment is optimized for each patient • In high need patients, treats until dry, enables monthly dosing and detects disease reactivations earlier. • In long durability patients, allows patients without active disease to safely to 6-month dosing. Quadrant of core unmet need We are expecting to close screenings for DAYBREAK by the end of August 30
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Tarcocimab in DR: the GLOW2 study in DR features a similar study design as the successful GLOW1 study, with the benefit of an additional 3rd initiating dose DRSS: diabetic retinopathy severity score; GLOW 1 study NCT05066230; GLOW2 study NCT06270836 Proportion of patients developing any sight- threatening complication from Baseline to Week 48 Key Secondary Endpoint ~90% risk reduction for developing a pre- specified sight- threatening complication with tarcocimab Primary Endpoint Tarcocimab demonstrated superiority in ≥2- step and ≥3-step improvement in DRSS Proportion of patients with ≥2-Step improvement in DRSS from Baseline to Week 48 GLOW1 study resultsGLOW2 study design Primary Endpoint Initiating doses 31
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Tarcocimab in DR: the GLOW1 study shows that tarcocimab opens the door to earlier treatment with only 2 doses a year – a transformative potential for millions of patients DR U.S. Prevalence 8,000,000 < 1% are currently treated due to treatment burden with existing anti- VEGF therapies 32 Microhemorrhages visible on the retina even if no visual symptoms are present yet Image from a patient in the Phase 3 GLOW1 study in diabetic retinopathy Baseline Image from same patient after treatment with tarcocimab Week 48 Tarcocimab has the potential to improve outcomes for millions of patients with only 2 doses a year* * after 3 initiating doses.
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Tarcocimab is uniquely poised to address the core unmet need in RVO with high efficacy and best-in-class durability Quadrant of core unmet need RVO: retinal vein occlusion; BRVO: branched retinal vein occlusion; 1. Durability interval calculated based on patients that received no injections (46%) or 1 injection (29%) over the second 6 months of Year 1. 2. RVO market size from imarc: RVO Market Size, Epidemilogy, In-Market drug sales, pipeline therapies, and Regional Outlook 0% 10% 20% 30% 40% 50% 1 2 3 4 5 6 7 8 9 10 11 Tarcocimab BRVO Tarcocimab All RVO Aflibercept BRVO Aflibercept All RVO Number of injections through Year 1 Proportion of subjects Tarcocimab 78% received ≤ 5 doses Aflibercept 93% received ≥ 6 doses Tarcocimab Number of doses in the second 6 months of Year 1 0-1 doses 75% 2 doses 18% 4-6 doses 2% 3 doses 5% 6-month durability 75% 1 Gen 1.5 agents have failed to address the key unmet need for high efficacy with better durability in RVO. With built-in durability, tarcocimab delivered 6-month durability in 75% of RVO patients in BEACON and is uniquely poised to address key unmet needs for RVO patients RVO market size: ~$3B 33
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Revisiting the core unmet need: based on a science of high immediacy and high durability, tarcocimab and KSI-501 are poised to fill the ‘golden quadrant’ Mainstay intravitreal biologic monotherapies for all patients Gen 1.0 • Eylea • Lucentis • Biosimilars Gen 1.5 • Eylea HD • Vabysmo Gen 2.0 – Kodiak Intravitreal Biologic KSI-501Tarcocimab Onerous monitoring and inflammation control. Long-term safety unknown Maintenance agents to be used in subset of patients, but always relying on mainstay biologics to (re)establish disease control Implants Gene Therapies Similar immediacy to Gen 1.0 therapies and longest durability for all patients Potential for additional efficacy beyond anti-VEGF monotherapies, while maintaining immediacy and signature durability of ABC® platform Efficacy Durability Quadrant of core unmet need Durability Efficacy 34
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35 KSI-101 Macular Edema Secondary to Inflammation (MESI)
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36 Macular Edema Secondary to Inflammation What is MESI?Sumit Sharma MD
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Macular edema, the common clinical presentation of a wide spectrum of diseases, can be caused by inflammation and/or by VEGF over-expression Inflammation driven VEGF driven Uveitis Systemic or Autoimmune Disease Inflammatory CNV Post Surgical Diabetic Macular Edema Retinal Vein Occlusion Neovascular AMD Myopic CNV AMD: age-related macular degeneration; CNV: choroidal neovascularization Macular Edema Spectrum of Diseases Macular edema secondary to inflammation Retinal vascular and degenerative diseases 37
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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 38 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
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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 39
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Macular edema is the leading cause of vision loss among patients with ocular inflammation Normal Retina on OCT Macular edema on OCT Fluid that leaked into the retina causing macular edema 1. Br J Ophthalmol. 2004;88(9):1159-1162. 2. Tomkins-Netzer O, et al. Ophthalmology. 2021 May;128(5):719-728. 40 • Noninfectious MESI represents a set of serious ocular inflammatory conditions that cause significant vision loss. • Ocular inflammation is the 4 th leading cause of vision loss among working aged adults in the developed world 1 • Approximately 1/3 of patients with ocular inflammation develop macular edema in the U.S.2 • Symptoms at diagnosis typically include distorted central vision, vitreous floaters, reduced visual acuity, and decreased color and contrast sensitivity • MESI leads to photoreceptor damage and can result in permanent loss of visual acuity
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41 Macular Edema Secondary to Inflammation What causes MESI?Sumit Sharma MD
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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 disease) can trigger intraocular immune responses and disrupt the blood-retinal barrier Blood-retinal barrier breakdown allows immune cells and plasma into the retina, causing leakage and macular edema 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. IL-6 and VEGF are co-induced: VEGF promotes vascular leak and neovascularization, while IL-6 sustains inflammation and upregulates VEGF 1 2 3 42
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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 uveitis1 VEGF levels in aqueous humor of uveitis patients with macular edema vs without macular edema2 43 • 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 VEGFIL-6 Both IL-6 and VEGF levels are elevated in patients who have ocular inflammation and macular edema
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0 10 20 30 40 50 0 50 100 150 Treatments Time (hrs) % Resistance Normal / Untreated VEGF IL-6/R VEGF + IL-6/R ↑ Treatment IL-6 and VEGF each disrupt the blood-retinal barrier independently. When combined, they cause an even greater loss of barrier integrity • Ocular inflammation damages tight junctions between endothelial cells, compromising the integrity of the blood retina barrier. This increases vascular permeability • The integrity of the blood-retinal barrier can be measured by barrier resistance • Exposure to both IL-6/R and VEGF additively induces greater loss in barrier function, as measured by decreased barrier resistance, than either IL-6 of VEGF alone, in human umbilical vein endothelial cells (HUVEC) Combination of IL-6/R + VEGF induces greater loss of barrier resistance and function than either VEGF or IL-6 aloneExposure start No exposure HUVEC cells were treated as indicated after growth to establish barrier 44 High barrier resistance from intact tight junctions Assessing vascular endothelial barrier integrity using electrical resistance measurements
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45 Macular Edema Secondary to Inflammation What is the unmet need? Sumit Sharma MD
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Corticosteroids are used most often for MESI, but carry significant safety risks and efficacy can be limited Most frequently prescribed medications in patients with macular edema due to noninfectious uveitis, across any line of therapy1 • Steroids were the most common medication class and remain the standard of care1 • XIPERE® (suprachoroidal triamcinolone acetonide) is the only approved local ocular treatment in the U.S. • Approximately 30-40% of patients do not fully respond to intraocular steroids 2,3 • Intraocular steroids are avoided in the pediatric population and used with caution in adults due to high risk of permanent glaucoma damage and cataract formation 1. Eichenbaum, D. et al. ARVO 2025 Poster Presentation 643. 2. Teper SJ. Journal of Clinical Medicine. 2021; 10(18):4133. 3. Tomkins-Netzer O et al. Ophthalmology. 2015. 122:2351 -2359. 46 73.3% Steroids
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My clinical experience: while topical steroids are the first line of therapy for MESI, only a third of patients achieve the treatment goal without the negative side effects 47 Sumit Sharma, MD ~1/3 Good responders Response to topical steroid treatment (diflupredprednate, Durezol) as first line of treatment in MESI patients ~1/3 Non responders and/or refractory ~1/3 Increased intraocular pressure ~2/3 of MESI patients require additional or alternative therapies after initial topical Durezol MESI patients
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Adverse effects from today’s treatments for MESI often require multiple surgical interventions, but surgeries are complicated in MESI patients and require complete control of inflammation before, during and after each procedure Visual damage from glaucoma is irreversible and can lead to legal blindness Cataract repair in MESI patients is complex and can be contraindicated, leading to permanent vision loss RETISERT® (fluocinolone acetonide intravitreal implant) label: • 60% of patients will require chronic IOP lowering medications to control intraocular pressure • 37% will require filtering procedures to control intraocular pressure • Within an average post- implantation period of approximately 2 years, nearly all phakic eyes are expected to develop cataracts and require cataract surgery RETISERT® (fluocinolone acetonide intravitreal implant) Prescribing Information. • Concerns about permanent IOP elevation limit steroid use and dose • Supplemental topical drops to control elevated IOP are often insufficient, requiring invasive glaucoma surgeries • Once the optic nerve is damaged due to glaucoma (high eye pressure), the visual loss is irreversible • Even with good inflammation control, surgeries can trigger intractable inflammation, often leaving the eyes with no intraocular lens implant and/or suboptimal results ((synechiae/scarring) 48
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Patient journey: steroids induced glaucoma with recurrent MESI over the course of approximately 2 years Failed treatments • Weekly adalimumab • Methotrexate • Cellcept • Azathioprine • Oral steroids • Difluprednate eyedrops Worsening macular edema with taper of difluprednate eyedrops Patient presented in August 2023 with a 12- year history of panuveitis of both eyes and multiple failed treatments Referred to a rheumatologist Referred to a glaucoma specialist Surgery #1: A combined cataract surgery and glaucoma surgery (OMNI canaloplasty) of the right eye in Jan 2024 IOP continue to rise despite surgery 1 Referred to a glaucoma specialist Surgery #2: Glaucoma tube shunt surgery of the right eye in May 2025 IOP now stable 2 Patient presented to uveitis specialist 3 4 Trial of bromfenac drops with initial improvement then worsening of macular edema IOP stable and macular edema now resolved after fluocinolone intravitreal injections Will evaluate further need for IMT next visit Developed worsening of chorioretinal lesions and macular edema Intraocular pressure (IOP) spikes to 40s with any steroids (topical eyedrops and intravitreal) For alternate immunomodulatory therapy (IMT) Attempted authorization for tocilizumab but insurance denied twice. Unable to get authorization for infliximab either Minimum macular edema initially Place back on difluprednate drops QID with spike of IOP to 38 49
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There is a core unmet need in MESI for a potent, high-strength, locally administered and safe therapy Safety Efficacy Illustrative IVT anti-VEGF monotherapy Systemic immuno- suppressants Steroids Core unmet need open High Fewer complications 50 • Targets both IL-6 and VEGF disease drivers • Potentially disease modifying • High strength • Potent • Minimally invasive • Better safety
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MERIT Study – Ozurdex (dexamethasone implant, Abbvie) does not resolve the edema in almost half of MESI patients at any point, and the treatment effect wanes by Week 12 51 Acharya NR, et al. Intravitreal Therapy for Uveitic Macular Edema-Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results. Ophthalmology. 2023 Sep;130(9):914-923. Even at the maximum drying effect of Ozurdex, which is observed at Week 8, the visual acuity gains are modest, and also wane by Week 12 -5 0 5 10 15 0 4 8 12 Dexamethasone implant Dexamethasone implant Letters Proportion of eyes with normalization of OCT CST Mean change in BCVA Patients, %
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MERIT Study –anti-VEGF monotherapy can provide a meaningful fluid response in a subset of MESI patients 52 Acharya NR, et al. Intravitreal Therapy for Uveitic Macular Edema-Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results. Ophthalmology. 2023 Sep;130(9):914-923. Dexamethasone implant Proportion of eyes with normalization of OCT CST Eyes, % Ranibizumab Methotrexate Dexamethasone implant Ranibizumab Methotrexate Anti-VEGF monotherapy (ranibizumab) can have a meaningful anatomical response in almost half of patients and completely resolve fluid in ~25% of patients Proportion of eyes with a meaningful OCT CST response Eyes with a ≥20% decrease in OCT CST, %
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DOVETAIL Study - intravitreal anti-IL-6 monotherapy (Roche, vamikibart) has been studied as a potential therapy for patients with inflammatory macular edema 53 Sharma, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 28 – August 1, 2023
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Vamikibart (Roche, anti-IL-6) has shown that anti-IL-6 monotherapy can provide visual and anatomical improvement in patients with inflammatory macular edema 54 Sharma, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 28 – August 1, 2023 A clear dose response is seen with IL-6 monotherapy in patients with inflammatory macular edema DOVETAIL Change from Baseline in BCVA DOVETAIL Change from Baseline in OCT CST
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55 While intravitreal IL-6 monotherapy is helpful, 50% of patients have persistent IRF1, similar to the overall failure rate of systemic adalimumab, leaving room for a more potent and/or broader spectrum biologic therapy 1. Jaffe et al. N Engl J Med. 2016. 375:932 -43. 2. Figure from Sharma, et al. A Novel Intravitreal Anti -IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 28 – August 1, 2023; Persistent intraretinal fluid (IRF) is known to cause permanent negative effects on visual function ~50% of patients have persistent IRF DOVETAIL Absence of IRF DOVETAIL Absence of SRF DOVETAIL ≥15-letter gainers at Week 12
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56 Sumit Sharma MD Macular Edema Secondary to Inflammation How can this unmet need be addressed?
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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-6IL-6 KSI-101: high formulation strength (100 mg/mL) 57
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-2 -1 0 1 2 3 0 50 100 150 Log inhibitor [nM] % Control -2 0 2 4 0 50 100 150 Log inhibitor [pM] % Control KSI-101 is a potent dual inhibitor of VEGF signaling and IL-6 classic (cis) and soluble (trans) receptor-mediated pathways KSI-101 inhibits VEGF signaling KSI-101 inhibits soluble IL-6 receptor-mediated signaling KSI-101 inhibits IL-6 classic signaling 0 1 2 3 4 5 0 200000 400000 600000 800000 Log inhibitor [pM] RLUs KSI-101 IC50 = 164 pM Aflibercept IC50 = 130 pM IC50 = 77 pM IC50 = 2.3 nM 58
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Bispecific KSI-101 improves barrier tight junctions greater than anti-IL-6 or anti-VEGF monotherapies alone Dual inhibition by KSI-101 confers superior normalization of complex tight junction-mediated barrier biology compared to either anti-VEGF or anti-IL-6 monotherapy alone Demonstrates the synergistic effect of IL-6 and VEGF dual inhibition RPE CellsVascular Cells B Anti-VEGF Anti-IL-6 KSI-101 Monotherapy Inhibition Dual inhibition No Inhibitors Exogenous VEGF and IL-6 Tight junction disruption and changes in cell morphology RPE cells: nuclei in blue, ZO1 (tight junction protein) in yellow. Red arrows indicate gaps in ZO-1 tight junction protein. Vascular cells: nuclei in purple, ZO1 (tight junction protein) in yellow, actin in green. 59Kodiak Data on File.
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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 60
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KSI-101 is poised to fulfill the core unmet need in MESI based on its potential to be a disease modifying, high-strength, locally administered and safe biologic Safety Efficacy Illustrative IVT anti-VEGF monotherapy Systemic immuno- suppressants High Less complications • Dual anti-IL-6 and anti-VEGF inhibition • Potential for disease modifying effect based on its synergistic inhibition of IL-6 and VEGF, as demonstrated in preclinical models and clinical cases • High strength formulation (100 mg/mL) and high potency provide the fire-power needed to treat “angry” inflammation and macular edema • Local (intravitreal) administration • Safety profile in line with intravitreally administered biologics (i.e., Eylea, Lucentis) Unified treatment irrespective of presumed etiology KSI-101 is designed to address the core unmet need Core unmet need open Steroids 61 • Targets both IL-6 and VEGF disease drivers • Potentially disease modifying • High strength • Potent • Minimally invasive • Better safety
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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 62
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63 Phase 1b APEX Study KSI-101 in DME and MESISumit Sharma MD
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Phase 1b APEX study: KSI-101 in patients with diabetic macular edema (DME) and macular edema secondary to inflammation (MESI) 64 • APEX is an ongoing, open label, multicenter platform study on the safety, tolerability, bioactivity, and pharmacokinetics of multiple intravitreal therapies in retinal diseases KSI-101 Multiple dose, dose-ranging study in 16 US sites Diabetic macular edema (first in human) Macular edema secondary to inflammation 41 patients treated (enrollment completed)12 patients treated (enrollment completed) Preliminary results are being presented. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. APEX 10 patients have completed the Study 1 patient has discontinued treatment - Lost to follow-up 1 patient is ongoing 10 patients have completed the Study 2 patients have discontinued treatment - 1 adverse event (uveitis flare-up consistent with underlying disease) - 1 withdrew consent 29 patients are ongoing Preliminary data presented today
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65 Diabetic Macular Edema Phase 1b APEX KSI-101 in DMESumit Sharma MD
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Phase 1b APEX study: a first in human study of KSI-101 in patients with DME End of Study Subjects with DME (n=12) Weeks 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg 66 KSI-101 injection Key inclusion criteria • Treatment-naive center-involving DME • OCT CST of ≥400 and ≤650 microns • BCVA score ≤75 and ≥25 (20/32 to 20/320 Snellen equivalent) Enrollment completed
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APEX KSI-101 in DME – Baseline Characteristics KSI-101 2.5 mg (n=4) KSI-101 5 mg (n=4) KSI-101 10 mg (n=4) All KSI-101 (N=12) Age, years, mean (SD) 54.5 (10.6) 68.3 (5.74) 56.5 (4.7) 59.8 (9.3) Female, n (%) 0 0 2 (50) 2 (16.7) Race, White, n (%) 4 (100) 4 (100) 4 (100) 12 (100) DME disease duration, months, mean (SD) 1.8 (1.6) 13.0 (22.0) 4.1 (3.1) 6.3 (12.7) BCVA, ETDRS Letters, mean (SD) 69.8 (3.3) 58.0 (13.9) 63.8 (9.9) 63.8 (10.4) Snellen equivalent ~20/40 ~20/63 ~20/50 ~20/50 OCT CST, µm, mean (SD) 442.0 (45.4) 483.0 (54.3) 485.8 (83.8) 470.3 (61.0) Lens Status, pseudophakic, n (%) 1 (25) 1 (25) 1 (25) 3 (25) 67 Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes all patients randomized. SD= standard deviation; BCVA= best corrected visual acuity; OCT= optical coherence tomograp hy; CST= central subfield thickness
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-250 -200 -150 -100 -50 0 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg -250 -200 -150 -100 -50 0 0 4 8 12 16 20 24 All KSI-101 APEX KSI-101 in DME – Meaningful anatomical gains were achieved with all KSI-101 dose levels tested 68Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes all available data by the 14 -Jul-25 cutoff date. Bioactivity was observed in all dose levels, with an apparent additional benefit obtained with the highest KSI-101 dose level (10 mg) Microns Weeks Treatment Phase Off-treatment Phase N values 2.5 mg 4 4 4 4 4 4 4 4 5 mg 4 4 4 3 3 3 3 3 10 mg 4 4 4 4 4 4 4 3 N values All KSI-101 12 12 12 11 11 11 11 10 Microns Weeks Mean Change in OCT CST by KSI-101 dose level Mean Change in OCT CST all KSI-101 dose levels combined Treatment Phase Off-treatment Phase
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0 5 10 15 20 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 All KSI-101 APEX KSI-101 in DME – Meaningful vision gains were achieved with all KSI-101 dose levels tested 69 While the 10 mg dose level seems to have an anatomical advantage, meaningful visual gains and bioactivity were observed in all dose levels Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes all available data by the 14 -Jul-25 cutoff date. ETDRS Letters Weeks Treatment Phase Off-treatment Phase N values 2.5 mg 4 4 4 4 4 4 4 4 5 mg 4 4 4 3 3 3 3 3 10 mg 4 4 4 4 4 4 4 3 N values All KSI-101 12 12 12 11 11 11 11 10 ETDRS Letters Weeks Mean Change in BCVA by KSI-101 dose level Mean Change in BCVA all KSI-101 dose levels combined Treatment Phase Off-treatment Phase
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APEX KSI-101 in DME – KSI-101 was well-tolerated KSI-101 2.5 mg (n=4) KSI-101 5 mg (n=4) KSI-101 10 mg (n=4) All KSI-101 (N=12) Summary of AEs in the Study eye, n (%) Subjects with ≥1 AEs 1 (25) 0 0 1 (8.3) Treatment-related AEs 0 0 0 0 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 0 0 0 AEs in the Study Eye, n (%) Intraocular inflammation 0 0 0 0 Occlusive retinal vasculitis 0 0 0 0 Cataract 0 0 0 0 Cataract traumatic* 1 (25.0) 0 0 1 (8.3) Elevated IOP 0 0 0 0 Eye Pain 0 0 0 0 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 70
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71 Macular Edema Secondary to Inflammation Phase 1b APEX KSI-101 in MESI Sumit Sharma MD
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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 72 KSI-101 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 completed
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APEX KSI-101 in MESI – Baseline Characteristics Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes all patients randomized. SD= standard deviation; BCVA= best corrected visual acuity; OCT= optical coherence tomograp hy; CST= central subfield thickness 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) 73
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200 300 400 500 600 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg -400 -300 -200 -100 0 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg APEX KSI-101 in MESI – Meaningful anatomical gains are rapidly achieved, with all dose levels achieving dryness OCT CST levels as early as Week 4 74 Microns Microns Mean Change in OCT CST in patients completing Week 12 Observed OCT CST over time in patients completing Week 12 2.5 mg 9 9 9 9 9 5 mg 8 8 8 8 8 10 mg 10 10 10 10 10 N values N values Weeks Weeks 2.5 mg 9 9 9 9 9 5 mg 8 8 8 8 8 10 mg 10 10 10 10 10 Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that comp leted the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) Dryness
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0 5 10 15 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg APEX KSI-101 in MESI – Meaningful visual acuity gains of more than two lines of vision have been achieved with the top two dose levels tested 75 ETDRS Letters ETDRS Letters 60 65 70 75 80 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg Mean Change in BCVA in patients completing Week 12 Observed BCVA over time in patients completing Week 12 Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that comp leted the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) 2.5 mg 9 9 9 9 9 5 mg 8 8 8 8 8 10 mg 10 10 10 10 10 N values N values Weeks Weeks 2.5 mg 9 9 9 9 9 5 mg 8 8 8 8 8 10 mg 10 10 10 10 10
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APEX KSI-101 in MESI – Half of patients have achieved a ≥15 letter gain, with an apparent additional benefit in the top two dose levels 76 Proportion of ≥15 letter gainers in patients completing Week 12 33 63 50 48 0 20 40 60 80 100 2.5 mg (n=9) 5 mg (n=8) 10 mg (n=10) All patients (n=27) Patients, % Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that comp leted the Week 12 visit by the cutoff date of 14-Jul-25 and meet all eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion)
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8 74 79 92 100 0 20 40 60 80 100 0 1 4 8 12 16 20 24 38 38 33 25 21N 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 Proportion of patients achieving absence of SRF Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only 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. 77 38 38 33 25 21N 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
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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 1 (7.7)a 2 (14.3) 2 (14.3) 5 (12.2) 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) Preliminary results. As 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 cell s and flare and 2+ vitreous haze prior to the Day 1 KSI-101 dose. The patient has safely received all 4 doses of KSI-101 and is +24 letters in BCVA at their last visit and no intraocular inflammatio n b Same patient. Uveitis flare-up consistent with underlying disease 78
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79 Macular Edema Secondary to Inflammation How does KSI-101 fit into the emerging treatment landscape? Sumit Sharma MD
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DOVETAIL vamikibart – approximately a quarter of patients exhibit a ≥15 letter gain with anti-IL-6 monotherapy 80 Sharma, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 28 – August 1, 2023 DOVETAIL vamikibart ≥15 letter gainers at Week 12
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The dual IL-6 and VEGF inhibition of KSI-101 seems to confer additional visual benefits in patients with MESI, with ~half of patients achieving a ≥15-letter improvement 81Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that comp leted the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) APEX KS1-101 ≥15 letter gainers in patients completing Week 12 33 63 50 48 0 20 40 60 80 100 2.5 mg (n=9) 5 mg (n=8) 10 mg (n=10) All patients (n=27) Patients, %
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82 DOVETAIL vamikibart – while intravitreal IL-6 monotherapy is helpful, 50% of patients have persistent IRF Sharma S, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From th e Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 28 – August 1, 2023; Persistent intraretinal fluid (IRF) is known to cause permanent negative effects on visual function DOVETAIL vamikibart Absence of IRF DOVETAIL vamikibart Absence of SRF ~50% of patients have persistent IRF
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8 74 79 92 100 0 20 40 60 80 100 0 1 4 8 12 16 20 24 38 38 33 25 21N 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 APEX KS1-101 Proportion of patients achieving absence of IRF APEX KS1-101 Proportion of patients achieving absence of SRF Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data c leaning. Includes only 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. 83 38 38 33 25 21N values Pooled KSI-101 APEX KSI-101 in MESI – the dual IL-6 and VEGF inhibition of KSI-101 seems to provide faster and better disease control, with a clear effect seen as early as Week 1
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200 250 300 350 400 450 500 550 Vamikibart KSI-101 KSI-101 rapidly dries the retina after a single injection -89 -136 -166 -4 -149 -187 4 -89 -180 -229 -183 Mean Change in OCT CST and absolute CST achieved by Week 4 OCT CST, microns Mean Change Baseline Legend DOVETAIL1 PEACHTREE2 MERIT3 APEX4 Dryness 84 0.25 mg n=12 1 mg n=12 2.5 mg n=13 2.5 mg n=9 5 mg n=8 10 mg n=10 Sham n=64 Xipere n=96 Ozurdex n=76 RBZ n=69 MTX n=76 Anti-IL-6 Anti-VEGF 1. Sharma S, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 2023. Mean values adapted from CST graph on slide 10. 2. Yeh S, et al. Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial. Ophthalmology. 2020 Jul;127(7):948-955 3. Acharya NR, et al. The MERIT Trial Results. Ophthalmology. 2023 Sep;130(9):914-923. Mean values adapted from Figure S3 (supplemental). 4. Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that completed the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) For illustrative purposes only. Not a head-to-head comparison. Differences exist between trial designs and subject characteristics, and caution should be exercised when comparing data across studies.
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200 250 300 350 400 450 500 550 Vamikibart KSI-101 Dual IL-6 and VEGF inhibition seems to provide a synergistic effect that results in additional anatomical benefits over either individual monotherapy -89 -136 -166 -4 -149 -187 4 -89 -180 -229 -183 0.25 mg n=12 1 mg n=12 2.5 mg n=13 2.5 mg n=9 5 mg n=8 10 mg n=10 Sham n=64 MTX DOVETAIL1 PEACHTREE2 MERIT3 APEX4 Mean Change in OCT CST and absolute CST achieved by Week 4 Anti-IL-6 Anti-VEGF RBZ n=69 OCT CST, microns Dryness Mean Change Baseline Legend 85 Anti-IL-6 monotherapy Steroids Anti-VEGF monotherapy Xipere n=96 Ozurdex n=76 1. Sharma S, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 2023. Mean values adapted from CST graph on slide 10. 2. Yeh S, et al. Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial. Ophthalmology. 2020 Jul;127(7):948-955 3. Acharya NR, et al. The MERIT Trial Results. Ophthalmology. 2023 Sep;130(9):914-923. Mean values adapted from Figure S3 (supplemental). 4. Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that completed the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) For illustrative purposes only. Not a head-to-head comparison. Differences exist between trial designs and subject characteristics, and caution should be exer- cised when comparing data across studies.
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KSI-101 provides continued disease control for MESI patients, as evaluated at Week 12 with the effect of 3 monthly doses 200 250 300 350 400 450 500 550 Mean Change in OCT CST and absolute CST achieved by Week 12 Vamikibart KSI-101 Dryness Mean Change Baseline Legend DOVETAIL1 PEACHTREE2 MERIT3 APEX4 -126 -189 -185 -16 -139 -174 -77 -209 -264 -199 86 -73 OCT CST, microns 0.25 mg n=12 1 mg n=12 2.5 mg n=13 2.5 mg n=9 5 mg n=8 10 mg n=10 Sham n=64 RBZ n=69 Anti-IL-6 Anti-VEGF Xipere n=96 Ozurdex n=76 RBZ n=69 MTX n=76 1. Sharma S, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 2023. Mean values adapted from CST graph on slide 10. 2. Yeh S, et al. Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial. Ophthalmology. 2020 Jul;127(7):948-955 3. Acharya NR, et al. The MERIT Trial Results. Ophthalmology. 2023 Sep;130(9):914-923. Mean values adapted from Figure S3 (supplemental). 4. Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that completed the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) For illustrative purposes only. Not a head-to-head comparison. Differences exist between trial designs and subject characteristics, and caution should be exercised when comparing data across studies.
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Dryness 200 250 300 350 400 450 500 550 Mean Change in OCT CST and absolute CST achieved by Week 12 Mean Change Baseline Legend Dual IL-6 and VEGF inhibition seems to provide a synergistic effect that results in additional anatomical benefits over either individual monotherapy DOVETAIL1 PEACHTREE2 MERIT3 APEX4 87 MTX Vamikibart KSI-101 0.25 mg n=12 1 mg n=12 2.5 mg n=13 2.5 mg n=9 5 mg n=8 10 mg n=10 Sham n=64 RBZ n=69 Anti-IL-6 Anti-VEGF Anti-IL-6 monotherapy Steroids Anti-VEGF monotherapy -126 -189 -185 -16 -139 -174 -77 -209 -264 -199 -73 OCT CST, microns Ozurdex n=76 RBZ n=69 Xipere n=96 1. Sharma S, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 2023. Mean values adapted from CST graph on slide 10. 2. Yeh S, et al. Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial. Ophthalmology. 2020 Jul;127(7):948-955 3. Acharya NR, et al. The MERIT Trial Results. Ophthalmology. 2023 Sep;130(9):914-923. Mean values adapted from Figure S3 (supplemental). 4. Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that completed the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) For illustrative purposes only. Not a head-to-head comparison. Differences exist between trial designs and subject characteristics, and caution should be exer- cised when comparing data across studies.
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88 In Summary: “Kodiak has designed a thoughtful bispecific trap- antibody-fusion protein. Early data from the Phase 1b APEX study are promising and show that –to date– the molecule appears safe and potent and to have a broad-spectrum activity in patients. I attribute this to the high strength and the dual anti-IL-6 and anti-VEGF mechanism. I see tremendous potential for KSI-101 to define a new treatment paradigm for patients with macular edema secondary to inflammation. The objective now is to reproduce this data in a pivotal program, in similar populations as the APEX study, and for the molecule to take a next step towards the commercial marketplace and the many general ophthalmology, retina and uveitis practices in need!” Sumit Sharma MD
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89 Macular Edema Secondary to Inflammation PEAK and PINNACLE KSI-101 Pivotal Program Charles Wykoff MD, PhD
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Phase 3 pivotal program in MESI – PEAK and PINNACLE Study Design Weeks D1 4 8 12 16 20 24 28 32 36 40 44 48 KSI-101 5 mg (n~50) KSI-101 10 mg (n~50) Sham (n~50) Primary endpoint KSI-101 5 mg injection Sham injection KSI-101 10 mg injection Individualized treatment (PRN) Sham PRN Fixed monthly dosing Individualized dosing PEAK and PINNACLE are actively enrolling 90 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) Individualized treatment criteria (Week 24-44) • Increase in OCT CST ≥50 µm compared to the lowest previous measurement, or • OCT CST >320 µm
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Phase 3 pivotal program in MESI – PEAK and PINNACLE Study Design Weeks D1 4 8 12 16 20 24 28 32 36 40 44 48 KSI-101 5 mg (n~50) KSI-101 10 mg (n~50) Sham (n~50) Primary endpoint KSI-101 5 mg injection Sham injection KSI-101 10 mg injection Individualized treatment (PRN) Sham PRN Fixed monthly dosing Individualized dosing PEAK and PINNACLE are actively enrolling 91 Rescue criteria • BCVA decrease ≥15 letters and CST worsening by ≥100 μm from Day 1, due to MESI. • Worsening of inflammation by ≥2 grade levels in anterior chamber cells and/or vitreous haze; or progression to grade 4. • The intraocular inflammation complications in the Study Eye did not improve and require rescue treatment to prevent irreversible loss of vision per Investigator’s judgment. Rescue Treatment allowed from Week 4 to Week 44, when warranted
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Phase 3 pivotal program in MESI – PEAK and PINNACLE Study Design PEAK PINNACLE Primary endpoint BCVA change from baseline to the average of Week 20 and 24 Key secondary endpoints Time to 15 letter gain Time to 15 letter gain Time to 15 letter loss Weeks D1 4 8 12 16 20 24 28 32 36 40 44 48 KSI-101 5 mg (n~50) KSI-101 10 mg (n~50) Sham (n~50) Primary endpoint KSI-101 5 mg injection Sham injection KSI-101 10 mg injection Individualized treatment (PRN) Sham PRN Fixed monthly dosing Individualized dosing PEAK and PINNACLE are actively enrolling 92
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Day 1 enroll in either study based on CST and BCVA Mild macular edema CST≥320 and <400 Moderate to severe macular edema CST ≥400 93 PEAK and PINNACLE – Key question: are these identical studies? PEAK Master Protocol Design A single screening process for both studies CST≥320 and BCVA 25-78 letters Mild to severe vision impairment BCVA 25-78 Moderate to severe vision impairment BCVA 25-70 Mild vision impairment BCVA 71-78 Based on the MESI patient population studied in APEX, two distinct and complementary sub-populations will be studied in PEAK and PINNACLE, allowing both studies to run concurrently in all study sites and covering a wide spectrum of MESI patients Moderate to severe edema with moderate to severe vision impairment Mild edema with any vision impairment Moderate to severe edema with good vision PINNACLE
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33 63 50 48 0 20 40 60 80 100 2.5 mg (n=9) 5 mg (n=8) 10 mg (n=10) All patients (n=27) PEAK and PINNACLE – Key question: Why are the APEX top two dose levels selected? 0 5 10 15 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg ETDRS Letters Weeks APEX Mean Change in BCVA in patients completing Week 12 The KSI-101 5 mg and 10 gm dose levels were selected to advance into PEAK and PINNACLE, based on: • Greater visual acuity gains achieved, particularly 15-letter gainers • Similar safety profile across all dose levels 2.5 mg 9 9 9 9 9 5 mg 8 8 8 8 8 10 mg 10 10 10 10 10 N values Patients, % APEX ≥15 letter gainers in patients completing Week 12 94Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that comp leted the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion)
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95 PEAK and PINNACLE – Key question: Why is mean change in BCVA the primary endpoint and not ≥15 letter gainers or losers? Evaluating mean change in BCVA as the primary endpoint maximizes the potential for both studies to be positive 0 5 10 15 0 4 8 12 16 20 24 5 mg 10 mg ETDRS Letters 5 mg 8 8 8 8 8 10 mg 10 10 10 10 10 N values APEX2 Mean Change in BCVA in patients completing Week 12 Weeks 0 5 10 15 0 4 8 12 16 20 24 Sham ETDRS Letters Cross-trial assessments should be interpreted with caution due to variouslimitations 1. Yeh S, et al. Efficacy and Safety of Suprachoroidal CLS -TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Rand omized Trial. Ophthalmology. 2020 Jul;127(7):948 -955 2. Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that comp leted the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) PEACHTREE1 Mean Change in BCVA in sham treated patients
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0 5 10 15 0 4 8 12 16 20 24 PEAK eligible 10 10 10 10 10 PINNACLE eligible 8 8 8 8 8 N values 96 PEAK and PINNACLE – Key question: Why is mean change in BCVA the primary endpoint and not ≥15 letter gainers or losers? Evaluating mean change in BCVA as the primary endpoint maximizes the potential for both studies to be positive ETDRS Letters APEX2 Mean Change in BCVA in patients that would meet criteria for PEAK or PINNACLE Week 12 completers Weeks 0 5 10 15 0 4 8 12 16 20 24 Sham ETDRS Letters PEAK eligible PINNACLE eligible Cross-trial assessments should be interpreted with caution due to variouslimitations 1. Yeh S, et al. Efficacy and Safety of Suprachoroidal CLS -TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Rand omized Trial. Ophthalmology. 2020 Jul;127(7):948 -955 2. Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that comp leted the Week 12 visit by the cutoff date of 14-Jul-25 and meet all the eligibility criteria. Excludes one patient in the 10 mg dose with a significant epiretinal membrane at baseline (exclusion criterion) PEACHTREE1 Mean Change in BCVA in sham treated patients
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PINNACLE 97 PEAK and PINNACLE – Key question: why are the key secondary endpoints different between PEAK and PINNACLE? PEAK The Key Secondary Endpoints are tailored specifically to the patient population included in their respective study Day 1 BCVA 75 CST 517 Week 4 BCVA +19 CST -234 Day 1 BCVA 67 CST 360 Week 4 BCVA +6 CST -81 Day 1 BCVA 54 CST 512 Week 4 BCVA +19 CST -234 Patient Population Treatment Objective Key Secondary Endpoint Moderate to severe edema with moderate to severe vision impairment Mild edema with any vision impairment Moderate to severe edema with good vision Macular edema resolution and vision improvement Macular edema resolution and vision maintenance Macular edema resolution and vision improvement Proportion of ≥15 letter improvement Proportion of ≥15 letter loss prevention Proportion of ≥15 letter improvement APEX Case Examples
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16 5 0 50 100 PEACHTREE (overall, n=64) PEACHTREE (US+Israel, n=40) 98 PEAK and PINNACLE – Key question: how do the APEX data educate the probability of success of PEAK and PINNACLE? The APEX data provide confidence in the probability of success of PEAK and PINNACLE, based on the predicate study PEACHTREE 80 25 0 50 100 PEAK eligible (n=10) PINNACLE eligible (n=8) APEX1 patients that would meet criteria for PEAK or PINNACLE Week 12 completers Proportion of patients (%) PEACHTREE2,3 patients treated with sham ≥15-letter gainers APEX1 patients that would meet criteria for PINNACLE Week 12 completers KSI-101 5 mg and 10 mg pooled PEACHTREE2 patients treated with sham Proportion of patients (%) 0 0 50 100 PINNACLE eligible (n=8) ≥15-letter losers Rescue medication over 24 weeks 72 0 50 100 PEACHTREE receiving rescue medication (overall, n=64) Improving vision Preventing vision loss Cross-trial assessments should be interpreted with caution due to variouslimitations 1. Preliminary results. As the APEX study is ongoing, final results may be different due to additional data collection or data cleaning. Includes only patients in the per protocol set that meet all the inclusion and exclusion 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. 2. Yeh S, et al. Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial. Ophthalmology. 2020 Jul;127(7):948-955 3. Xipere FDA Center for Drug Evaluation and Research Biologics Licensing Application Statistical Review. Application number 211950Orig1s000
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99 PEAK and PINNACLE – Key question: Why are the primary and key secondary endpoints evaluated up to Week 24 and not at Week 16? Optimizing the timing of the primary and key secondary endpoints from Week 16 to Week 24, maximizes the vision gains (mean change and categorical) 0 5 10 15 20 25 30 0 4 8 12 16 20 24 Evaluating the key secondary endpoints over time maximizes the chance of capturing the categorical change and thus, meeting the key secondary endpoint Patient treated with KSI-101 5 mg APEX Case Example Vision continues to improve over time Using a single timepoint (Week 16) to evaluate ≥15 letter gains reduces the chances of capturing the categorical change +15 +14 +25 +28 Change in BCVA at Week 16: +14 ≥15 letter gainer at Week 16: no Change in BCVA at Week 20 and 24: +26.5 ≥15 letter gainer up to Week 24: yes Preliminary results. As the APEX study is ongoing, final results may be different due to data cleaning. Change in BCVA, letters
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MESI is a heterogeneous spectrum of diseases with a common clinical presentation and a common pathophysiology. KSI-101 has the potential to become the first line common therapy for MESI Macular Edema Blood Retinal Barrier Disruption VEGF IL-6 IL-6 KSI-101 Common Clinical Presentation Common Pathophysiology Potential common therapy Angiogenesis Inflammation Normal Retina after a single injection of KSI-101 10 mg 100
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101 A Patient’s MESI Journey Dolly S. Chang, MD, PhD Chief Scientific Officer
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102 Kodiak, Ophthalmologist and Glaucoma Surgeon Dolly S. Chang, MD, PhD Chief Scientific Officer, Kodiak Sciences Inc. Ophthalmologist, Glaucoma Surgeon Adjunct Clinical Assistant Professor of Ophthalmology, Stanford University • At Kodiak, Dr. Chang oversees pipeline development and advances transformative therapies for retinal disease • Prior to Kodiak, Dr. Chang was Group Medical Director at Genentech Research and Early Clinical Development (gRED), where she steered development programs through translational and clinical stages and championed new therapeutic areas including glaucoma neuroprotection • Dr. Chang holds a position as Adjunct Clinical Assistant Professor at Stanford University’s Byers Eye Institute, continuing her clinical practice in cataract and glaucoma surgeries 102
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Patient journey #1: “a crazy amount of eye drops for macular edema and inflammation” – a physician's perspective as a patient “I had macular edema that rose and fell with each flare, and I went through what felt like a million OCTs. The only treatment was Durezol eyedrops, which kept the inflammation in check, but it came at a cost—my eye pressure spiked, and I developed glaucoma. In addition to Durezol, I was juggling three pressure-lowering drops, plus a non-steroidal and a dilating drop to prevent scarring. That became my routine that was exhausting to manage, even as a physician. I was never treated with intravitreal steroids.” Patient’s eyedrop schedule Morning Noon Afternoon Evening Difluprednate Ketorolac Cyclopentolate Brimonidine Timolol Dorzolamide 103
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36% 24% 40% 0% 20% 40% 60% 80% 100% Limited resolution and IOP risk highlight limitations of steroid eyedrops in MESI Am J Ophthalmol 2018 Jul: 191:14-22; Am J Ophthalmol. 2022 Aug:240:232-238 Good response Partial response Refractory 32% 0% 20% 40% 60% 80% 100% IOP elevation 32% of patients on Durezol drops had an IOP response that is clinically concerning In 36% of patients, topical steroids (difluprednate, Durezol) controlled the disease. In 40% of patients, the disease was refractory to steroid drops 104
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Patient journey #2: 52-year-old healthy woman with bilateral blurry vision and floaters No prior ocular history, only requires reading glasses Eye examination: • Vision OD 20/32 & OS 20/25, normal eye pressure • Mild anterior segment inflammation, vitritis • Scattered yellowish-white retinal lesions Ocular imaging: • OCT: no thickening at presentation • Fluoresceine angiography: peripheral vasculitis Physical exam Differential Diagnosis Rashes/lesions/ulcers Behcet’s, psoriasis, VKH, Lupus, herpes Joints/arthritis/spine mobility RA, ankylosing spondylitis, reactive arthritis Lymphadenopathy Sarcoidosis, infection, lymphoma Neurological deficits/headache MS, neurosarcoidosis, VKH, Behçet's, syphilis Gastrointestinal system IBD Laboratory/Systemic Imaging CBC/DC For all uveitis ESR, CRP For all uveitis HLA-A29 Birdshot ACE/Lysozyme Sarcoidosis Chest X-ray or CT Sarcoidosis RPR, VDRL, FTA-ABS Syphilis PPD TB QuantiFERON TB Chest X-ray TB Lyme antibodies Lyme This patient illustrates the diagnostic complexity of non-infectious uveitis—a broad work-up was negative except for HLA-A29+, which, with the presence of chorioretinal lesions, leading to a diagnosis of birdshot chorioretinopathy, a chronic, bilateral posterior uveitis This representative case is based on Dr. Quan Nguyen’s clinical experience, literature, and reviewed by uveitis consultants. Int Med Case Rep J. 2025 Mar30;18:445-460. J Ophthalmic Inflamm Infect 2025 Mar 13;15(1):25; Clin Ophthalmol. 2013 Dec 18;8:73-81 105
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0 100 200 300 400 500 600 7000.00 0.10 0.20 0.30 0.40 0.50 0.60 0 2 4 6 8 10 12 14 16 18 20 Treatment today is complex: MESI can persist and recur despite inflammation resolution and multiple therapies Months CST Visual Acuity 20/20 20/25 20/32 20/40 20/50 20/63 20/80 This representative case is based on Dr. Quan Nguyen’s clinical experience, literature, and reviewed by uveitis consultants. Int Med Case Rep J. 2025 Mar30;18:445-460. J Ophthalmic Inflamm Infect 2025 Mar 13;15(1):25; Clin Ophthalmol. 2013 Dec 18;8:73-81 Multiple systemic therapies to control inflammation • Initiate oral prednisone 60 mg, significant weight gain • Oral prednisone tapered, and methotrexate (MTX) added Macular edema develops despite Control of inflammation • Received 3 cycles of monthly IV methylprednisone due to MESI • Started adalimumab, discontinued due to cutaneous reaction • Switched to mycophenolate mofetil 1500mg BID Vision drops and MESI persists; introduce 1 st Ozurdex MESI temporarily responds to Ozurdex Fluid reoccurs; 2nd dose of Ozurdex Cataract developed and fluid reoccurs; 3rd dose of Ozurdex VA CST Fluid responded, but patient needed a combined glaucoma and cataract surgery MESI temporarily responds to Ozurdex Both eyes underwent a similar clinical course, only right eye is shown here 106
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When steroids help and harm: the challenge of managing glaucoma in MESI patients requiring ocular steroids 0 20 40 60 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 Intraocular Pressure Maximum glaucoma medications given but eye pressure still too high Combined glaucoma tube shunt surgery + complex cataract surgery After surgery, inflammation flared up and eye pressure was still elevated which led to irreversible vision loss from glaucoma The stronger the steroid, the stronger the side effects For example, RETISERT® (fluocinolone acetonide intravitreal implant) label: • 60% of patients will require chronic IOP lowering medications to control intraocular pressure and 37% will require filtering procedures to control intraocular pressure • Within an average post- implantation period of approximately 2 years, nearly all phakic eyes are expected to develop cataracts and require cataract surgery 107 This representative case is based on Dr. Quan Nguyen’s clinical experience, literature, and reviewed by uveitis consultants.
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Toward unified MESI management: can KSI-101 deliver potency without the glaucoma and surgical burden of steroids? • Idiopathic • Vogt-Koyanagi-Harada disease • Behcet's disease • HLA-B27 associated • Juvenile idiopathic arthritis • Multiple sclerosis • Pars planitis • Birdshot chorioretinopathy • Multifocal choroiditis • Sarcoidosis • Refractory Irvine Gass syndrome Complex Diagnosis Considerations in Steroid Selection • Glaucoma history, steroids intraocular pressure response • Phakic versus pseudophakic • Location of the primary inflammation • Unilateral versus bilateral • Prior response/fellow eye response • Inflammation active versus inactive • Chronicity of the MESI • Vision • Age Complex Treatment Decisions Treat with intravitreal biologic KSI-101 Simplified Diagnosis and Treatment Journey Diagnosis MESI with OCT Today 108 Patients are not undertreated due to side effects of steroid use Patients can achieve disease remission and/or chronic disease control
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109 KSI-101 commercial opportunityVictor Perlroth, MD Chairman and CEO
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Problem Statement: Ocular inflammation is the 4th leading cause of blindness among the working-age population in the developed world MESI, a serious complication of ocular inflammation, is the primary contributor to vision loss and blindness in this group Br Journal of Ophthalmology 1996;80:844-848, Ophthalmology. 2021 May;128(5):719-728, Orphanet J Rare Dis. 2012 Aug 29:7:57 110
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A chronic retinal condition that occurs when inflam- mation (past or present) disrupts the blood-retinal barrier triggering edema, and leading to serious risk of vision loss MESI can be triggered by a variety of underlying systemic and local autoimmune conditions and represents a prevalence of 450,000 patients in the US of which ~300,000 are trial-eligible A serious vision threatening disease The initial KSI-101 addressable population is the >150,000 MESI patients in the US who are contraindicated for intraocular steroid inject- tions, at risk of glaucoma or cataract development due to chronic steroid treatment or are refractory from chronic steroid treatment Over time, avoiding the consequences of longer- term steroid use together with SOC matched efficacy can support a first-line therapeutic of choice profile for KSI-101 >150,000 initial KSI-101 addressable MESI patients in the US KSI-101 is in development for the treatment of MESI: • Locally injected • Potent • High-dose • First-in-class anti-IL6 and VEGF trap • Bispecific protein M I Historically, physicians segment and treat patients based on presumed etiology, resulting a lengthy trial and error patient journey KSI-101 offers the promise of simplifying the MESI diagnostic and patient journey, upgrading the ophthalmologist as the primary ocular caregiver, and improving patient outcome across etiologies Differentiated potent high strength dual MOA Interviewed physicians are impressed by the KSI-101 safety and efficacy product profile, noting that it lacks the serious negative consequences of chronic steroid use, including glaucoma and cataract, but has strong efficacy across etiologies on par with current intraocular steroids E S Potential for a simplified and safer MESI patient journey I Excitement from physician interviews 111
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MESI affects ~450,000 US patients (~300,000 trial eligible), estimated by two methodologies and often reported by etiology (defined autoimmune, idiopathic, procedural, infectious and other) Total ME wAMD- ME DME RVO-ME Other Non- MESI1 MESI ~5,415 ~1,665 ~1,485 ~1,450 ~360 ~455 ~455K out of 5.4M ME patients in the U.S. may be classified under the “MESI” definition, ~298K meet KSI-101 trail inclusion U.S. MESI EPIDEMIOLOGY (2025) Thousands of patients Note: 1 Other Non-MESI includes epiretinal membrane ME and RP-associated ME; 2 Non-exhaustive list, other types include laser photocoagulation, DMEK, DSEAK-ME, IOL replacement, scleral buckling, pneumatic retinopexy; 3 Non-exhaustive list, others include birdshot choroidopathy, multiple evanescent white dot syndrome, punctate inner choroidopathy, and more; 4 Non-exhaustive list, others include bartonella sp. Tuberculosis, endophthalmitis; DME = Diabetic Macular Edema; ERM = Epiretinal Membrane; HLA = Human Leukocyte Antigen, ME = Macular Edema; MESI = Macular Edema Secondary to Inflammation; RP = Retinitis Pigmentosa; RVO = Retinal Vein Occlusion; RVO = Retinal Vein Occlusion; UME = Uveitic Macular Edema; wAMD = Wet Age-Related Degeneration Source: See appendix POST-PROCEDURAL ME2 Pars Plana Vitrectomy ~60K Glaucoma surgery ~50K Cataract surgery ~30K DEFINED AUTOIMMUNE ME3 HLA-B27 ~20K Multiple sclerosis ~10K Idiopathic Multifocal Choroiditis ~7K Serpiginous choroidopathy ~6K Vogt-Koyanagi-Harada ~4K Ankylosing spondylitis ~15K OTHER MESI Scleritis ~10K Inflammatory CNV ~6K Sarcoidosis ~7K ~145 ~180 ~80 ~20 ~30 MESI Post-Procedural (Refractory ~32K) * Idiopathic (etiology unknown)* Defined Autoimmune Related* Other MESI (inflammatory CNV ~6K) * Infectious 4 (Excluded from KSI-101 trials) * = KSI-101 PEAK and PINNACLE TRIAL INCLUSION Method 1 Method 2 Post-Procedural (Acute ~113K) Other MESI 112
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# of Patients 300K Total trial eligible patient prevalence Today, treated with topical steroids and/or oral immunosuppressants1 Contraindicated for intraocular steroids Today, treated with single intraocular steroid injection Treated with multiple intraocular steroid injections Refractory to intraocular steroids 1L (4-6 weeks) 2L (~3 months) 3L (6+ months) Note: 1 First line includes eye drops or systemic immunnosuppressants. Eyedrops prescribed by physicians includes steroidal and non-steroidal anti-inflammatory drops; IO = Intraocular; ME = Macular Edema; MESI = Macular Edema Secondary to Inflammation; Source: Bellocq et al., BMJ (2014); Birnbaum et al., JAMA Ophthalmol. (2011); Erden et al., Ocular Immunol. Inflamm. (2019); Kao et al., A.A. Ophthalmol. (2022);Expert Interviews (JUN 2025); MUST Research Group, Ophthalmol. (2019); Schallhorn et al., Am. J. Ophthalmol. (2018) KSI-101 initial addressable population is >150,000 KSI-101 initial addressable population is greater than 150,000 MESI patients in the US Example therapies: KSI-101 ADDRESSABLE POPULATION Total MESI prevalence 455K 298K 34K 153K 25K 157K 16K 70K Minus Acute post- procedural and infectious >150,000 113
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Other MESI1 * Infectious Defined Autoimmune-Related2 * Idiopathic (etiology unknown) * Post-procedural* Other ME RVO-ME DME wAMD-ME Most MESI patients are in the care of General Ophthalmologists and Retinal Specialists; complex cases are referred out to Uveitis Specialists 17% of retina specialists’ current case load is MESI today 31% 27% 27% 7% U.S. Prevalence 26% 29% 14% 5% 13% 6% General Opthalmologist 31% 31% 14% 7% 6% 5% Retinal Specialist 18% 34% 7% 5% 10% 7% 15% Uveitis Specialist Notes: 1Other causes can include RP, scleritis, neoplasms, drug-induced, and trauma-induced; 2 Non-exhaustive drivers include sarcoidosis, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, Behcet’s disease, Vogt-Koyanagi-Harada disease, and others; trauma-induced; DME = Diabetic Macular Edema, ERM = Epiretinal Membrane, ME = Macular Edema, MESI = Macular Edema Secondary to Inflammation, RP = Retinitis Pigmentosa, RVO = Retinal Vein Occlusion, wAMD = Wet Age-Related Degeneration Source: Expert Interviews (JUN 25); Review of Optometry (2024); Ho and Avery, Retina Today (2025); Tsui et al., J Acad Ophthal (2022) MESI INDICATIONS: • General ophthalmologists act as the referral gatekeepers, being the most common physician subtype (~18K in the U.S.) • Retinal specialists (~3K in the US) tend to treat a diverse set of macular edema patients (~17% of their current case load is MESI today) • Uveitis specialists are rare (~200 in the U.S.) but are the most familiar with MESI subtypes as it makes up ~40% of their practice OPHTHALMOLOGY PRACTICE BREAKDOWN % of ME patients by patient subtype across physician types 8% 26% 17% 40% * KSI-101 TRIAL INCLUSION 114
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Physicians are impressed with both the rapid response by Week 4 and the diversity of etiologies responding to KSI-101 115 “… It’s not much different than using anti-VEGF to treat DME, AMDs, and RVOs. Those are very different diseases with very different pathophysiology but at the end of the day the medicine is the same and it works well in all three diseases. […] I didn't see that before—but seeing these pictures and seeing the data that you showed me on the slide I don't see a reason not to.…” – Retinal Specialist
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Patients typically present with central vision loss or distortion, and ophthalmologists conduct routine workup and targeted tests MESI DIFFERENTIAL DIAGNOSIS PATIENT ARRIVES IN CLINIC • Blurry vision • Metamorphopsia • Floaters May or may not come from referral upstream ROUTINE WORKUP • Clinical history & symptoms • Ocular exam1 • OCT2 • Fluorescein angiography TARGETED TESTS • Targeted lab tests for infection (e.g., toxoplasmosis, syphilis, TB) • Systemic workup for autoimmune markers (e.g., HLA-B27 typing, X-ray, MRI) SYMPTOM CHARACTERIZATION • Is the vision loss central or peripheral? Central vision loss may implicate pathology affecting the macula • Is vision loss unilateral or bilateral? Unilateral may suggest an acute inflammatory or vascular event; bilateral may suggest systemic or chronic pathology • Where is the uveitis? Anterior, intermediate, posterior, and panuveitis ETIOLOGICAL CLARIFICATION • Is there an underlying systemic disease? E.g., diabetes, autoimmune • Is there a known inflammatory condition? E.g., uveitis, autoimmune, TB, syphilis, herpes • Has there been recent intraocular surgery? E.g., cataract • Has the patient used medications known to induce macular edema? E.g., prostaglandins, interferons Note: 1 Evaluate anterior chamber cells, vitreous haze, and other signs of intraocular inflammation; 2 Identifies intraretinal cysts, subretinal fluid, and central sub-foveal thickness; HLA = Human Leukocyte Antigen, OCT = Optical Coherence Tomography, TB = Tuberculosis; Source: American Academy of Ophthalmology; Expert Interviews (JUN 2025) 116
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MESI is diagnosed via dilated fundus exam & OCT, with subtypes often distinguished through clinical history and targeted lab testing Note: 1 Used to evaluate anterior chamber cells, vitreous haze, and other signs of intraocular inflammation; 2 Identifies intraretinal cysts, subretinal fluid, and central sub foveal thickness; HLA = Human Leukocyte Antigen, ME = Macular Edema; MESI = Macular Edema Secondary to Inflammation, OCT = Optical Coherence Tomography, TB = Tuberculosis Source: American Academy of Ophthalmology; Expert Interviews (JUN 2025) • Clinical presentation indicative of infection (e.g., toxoplasmosis scar) with unilateral ME presentation • Targeted lab tests for infection (e.g., toxoplasmosis, syphilis, TB) • History of recent cataract surgery with symptoms presenting after an initial good post-op recovery followed by 4 – 6+ months of refractory response to topical steroid drops • History of systemic disease and / or symptoms suggestive of autoimmune disease (e.g., joint pain, rashes) • Systemic workup for autoimmune markers (e.g., HLA-B27 typing, X- ray, MRI) and fluorescein angiography for inflammatory leakage • Diagnosis of exclusion, where ME cannot be attributed to autoimmune, infectious, post-procedural, or other causes (e.g., medication- or trauma-induced) MACULAR EDEMA SECONDARY TO INFLAMMATION Idiopathic (etiology unknown) Defined autoimmune- related Post-procedural (refractory) Infectious INITIAL WORKUP DIFFERENTIAL DIAGNOSIS • Clinical History & Symptoms: Presents with blurred vision, central blind spots, or vitreous floaters • Ocular Examination: Standard dilated fundus exam and slit-lamp bio- microscopy 1 • OCT2: Confirms presence, location, and severity of ME • Fluorescein Angiography: Identifies inflammatory leakage pattern to aid in differential diagnosis MESI DIAGNOSIS BY SUBTYPE OVERVIEW 117
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Physicians were open to using KSI-101 after eye drops and before steroid injections; Uveitis Specialists may use first-line in severe cases Note: 1 Cases tend to be more severe and bilateral warranting systemic immunosuppressants (e.g., methotrexate, adalimumab, tocilizumab) and often prescribed in coordination with a rheumatologist; 2 Majority of cases are resolved with anti-infective treatments; 3 Steroids cautiously introduced after infection control, some specialists may progress to IVT or oral steroids if inflammation persists, but do so cautiously; 4 KSI-101 placement in infectious ME is more variable, some physicians will use in place of steroids, others try to avoid ocular injections after recent infection, and others prefer drops / oral therapies that can be removed quickly in case infection re-emerges; IVT = Intravitreal Injections; ME = Macular Edema; NSAID = Non-Steroidal Anti- Inflammatory Drug; Source: Expert Interviews (JUN 2025) TREATMENT PARADIGM EVOLUTION • KSI-101 is generally considered early second line, but may be first-line in patients with more severe disease or contra- indications to steroids Topical NSAIDs Topical steroids Systemic immunosuppressants1 Topical NSAIDs Topical steroids Periocular steroid Periocular steroid Anti-infectives2 MACULAR EDEMA SECONDARY TO INFLAMMATION Idiopathic Autoimmune-related Post-procedural Infectious IVT steroid injections Systemic immunosuppressants IVT steroid injections ILLUSTRATIVE Topical steroids3 IVT or oral steroids3 KSI-101 “… [I’d use Product X in] patients who fail my first line with topical therapy. I might think of this as second line, maybe instead of going to a triamcinolone injection or a dexamethasone implant …” – Retina Specialist KSI-101 KSI-1014 “… If they are younger, phakic, I will try [Product X] first …” – Retina Specialist Placement certainty: Consensus Varied perspectives 118
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119 Summary Victor Perlroth, MD Chairman and CEO
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• Strong 12-week data from Phase 1b APEX • PEAK and PINNACLE – already enrolling • Commercial opportunity of 150,000+ initial addressable patients with headroom • Science-based “heavyweights”? • Tarcocimab: targeting BLA mid-2026 in wet AMD, RVO and diabetic retinopathy • KSI-501: bispecific ABC® may be even better! • KSI-102, KSI-103: bispecifics for inflammation • Duets for glaucoma and geographic atrophy • VETi: AI headsets for commercial leadership • URSUS: commercial manufacturing A potent reason to believe in Kodiak 2 options in the $15+ billion anti-VEGF market Accelerating our technology and product leadership in retina KSI-101 Tarcocimab & KSI-501 Pipeline, Digital Health, Manufacturing Wholly Owned Kodiak Investor R&D Day July 2025 – Key Messages 120 . AMD: age-related macular degeneration; RVO: retinal vein occlusion; ABC: antibody biopolymer conjugate
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Q&A 121