Kodiak Sciences Inc · NASDAQ:KOD
Kodiak Sciences — International Ocular Inflammation Society 2025
39 slides from Kodiak Sciences's conference presentation, 2025
Slide 1: A First-in-Class Investigational Bispecific Intravitreal Biologic for MESI
THE OPHTHALMOLOGY MEDICINES COMPANY A First-in-Class Investigational Bispecific Intravitreal Biologic for the Treatment of Macular Edema Secondary to Inflammation (MESI) International Ocular Inflammation Society 2025
Slide 2: Forward-Looking Statements
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
Slide 3: Kodiak Today
Victor Perlroth, MD CEO, Kodiak Sciences Kodiak Today 3
Slide 4: Kodiak pipeline and platform highlights
Dedicated commercial scale manufacturing BLA filing Visual engagement Robust pipeline Three late-phase facility preparation platform program clinical assets Advancing in Custom designed, On track towards Visual engagement Kodiak’s next set of parallel across a commercial scale our goal of filing a t
Slide 5: Kodiak is a precommercial, retina-focused biotech with a maturing portfolio
Kodiak is a precommercial, retina-focused biotech with a maturing portfolio in retinal vascular disease and in ocular inflammation MOA Indication/MOA Pre-clinical Pre-IND Phase 1/2 Phase 3 • GLOW1 primary endpoint met Diabetic Retinopathy • GLOW2 topline data expected Q1 2026 Anti-VEGF Antibody • DA
Slide 6: Three late-stage clinical assets across a broad spectrum of retinal diseases
Three late-stage clinical assets across a broad spectrum of retinal diseases Phase 3 Phase 3 / First-in-class Phase 1b / First-in-class TARCOCIMAB KSI-501 KSI-101 Anti-VEGF ABC® for patients with Anti-IL-6 VEGF trap bispecific ABC® for High-strength anti-IL-6 anti-VEGF retinal vascular disease patie
Slide 7: KSI-101
Lyndell Lim MBBS, DMedSci KSI-101 A First-in-Class Investigational Bispecific Intravitreal Biologic for the Treatment of Macular Edema Secondary to Inflammation (MESI) 7
Slide 8: Macular edema is the leading cause of vision loss among patients with ocular inflammation
Macular edema is the leading cause of vision loss among patients with ocular inflammation Normal Retina on OCT • Ocular inflammation is the 4th leading cause of vision loss among working aged adults in the developed world1 • Approximately 1/3 of patients with ocular inflammation develop macular edem
Slide 9: IL-6 and VEGF drive fluid accumulation in the retina
IL-6, a proinflammatory cytokine, and VEGF play key roles in driving the accumulation of fluid in the retina IL-6 Pathway VEGF Pathway VEGFR IL-6 Rα gp130 Endothelial Vascular Endothelial Endothelial Endothelial Activation Hypertrophy Survival Proliferation Migration Vascular Immune Cell Vascular En
Slide 10: Both IL-6 and VEGF levels are elevated in ocular inflammation and macular edema
Both IL-6 and VEGF levels are elevated in patients who have ocular inflammation and macular edema IL-6 VEGF • IL-6 levels are elevated in patients with ocular • Persistent inflammation triggers VEGF inflammation and further elevated in patients upregulation. VEGF levels are found to be elevated with
Slide 11: IL-6 and VEGF each disrupt the blood-retinal barrier independently
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 Treatments Exposures tight junctions between 300 endothelial cells, compromising No exposure Normal / Untreated the integrity of the B
Slide 12: Vamikibart anti-IL-6 monotherapy improves vision and anatomy in inflammatory macular edema
Vamikibart (Roche, anti-IL-6) has shown that anti-IL-6 monotherapy can provide visual and anatomical improvement in patients with inflammatory macular edema Change from Baseline in BCVA Change from Baseline in CST A clear dose response is seen with IL-6 monotherapy in patients with inflammatory macu
Slide 13: IL-6 monotherapy leaves about 50% of patients with persistent IRF
While intravitreal IL-6 monotherapy is helpful, 50% of patients have persistent IRF, similar to the overall failure rate of systemic adalimumab1, leaving room for a more potent therapy ~50% of patients have persistent IRF Persistent intraretinal fluid (IRF) is known to cause deleterious and permanen
Slide 14: KSI-101 is a first-in-class, high-strength intravitreal biologic
KSI-101 is a first-in-class, high-strength intravitreal biologic designed to target IL-6 mediated inflammation and VEGF-mediated vascular permeability simultaneously KSI-101: high formulation strength (100 mg/mL) VEGF IL-6 IL-6 14
Slide 15: KSI-101 is a potent dual inhibitor of VEGF and IL-6 signaling
KSI-101 is a potent dual inhibitor of VEGF signaling and IL-6 classic (cis) and soluble (trans) receptor-mediated pathways KSI-101 inhibits IL-6 KSI-101 inhibits soluble IL-6 KSI-101 inhibits VEGF classic signaling receptor-mediated signaling signaling 150 IC50 = 77 pM 150 IC50 = 2.3 nM KSI-101 IC50
Slide 16: KSI-101 improves barrier tight junctions more than monotherapies
Bispecific KSI-101 improves barrier tight junctions greater than anti-IL-6 or anti-VEGF monotherapies alone Exogenous VEGF and IL-6 Normal Tight junction disruption and changes in cell morphology Monotherapy Inhibition Dual inhibition No Inhibitors Anti-VEGF Anti-IL-6 KSI-101 Dual inhibition by KSI-
Slide 17: KSI-101 restores barrier resistance from pre-existing insult
Bispecific KSI-101 restores barrier resistance from pre-existing insult greater than anti-IL-6 or anti-VEGF monotherapies alone 150 High barrier resistance Intact tight junctions No Exposure No Exposure VEGF + IL-6/R VEGF ++ KSI-101 IL-6/R + KSI-101 KSI-101 restores barrier integrity to 100 % Resist
Slide 18: KSI-101 for the Treatment of MESI
KSI-101 for the De-Kuang Hwang Treatment MD, PhD of MESI Macular Edema Secondary to Inflammation 18
Slide 19: KSI-101 is being developed for macular edema secondary to inflammation
In the universe of macular edema, KSI-101 is being developed for the treatment of macular edema secondary to inflammation (MESI) Driver is Inflammation Anti-VEGF Approved Idiopathic Diabetic Macular Edema Uveitis (cells in the eye) Retinal Vein Systemic or Macular Edema Occlusion Autoimmune Disease
Slide 20: Risk factors for developing Macular Edema Secondary to Inflammation
There are several risk factors that increase the likelihood of developing Macular Edema Secondary to Inflammation Risk factors for the development or progression of MESI: Autoimmune Nonanterior Female or systemic ocular Patients that develop disease inflammation MESI tend to have an increased suscep
Slide 21: MESI is clinically unified but etiologically diverse
MESI has a heterogenous patient population. Case examples demonstrate how MESI is clinically unified but etiologically diverse Potential causes of MESI • Macular edema is the leading cause of vision loss in patients Uveitis with uveitis, often referred to today as uveitic macular edema Systemic / •
Slide 22: Corticosteroids are used most often for MESI but carry safety risks
Corticosteroids are used most often for MESI, but carry significant safety risks and efficacy is limited Most frequently prescribed steroid and nonsteroid for uveitic macular edema, a form of MESI, medications across any line of therapy1 • Steroids were the most common medication class and remain th
Slide 23: Treatments for MESI today are suboptimal, often leading to complications
Treatments for MESI today are suboptimal, often leading to complications Cataract in uveitis RETISERT® (fluocinolone acetonide Glaucoma surgery is invasive intravitreal implant) label: patients is complex • 60% of patients will require chronic IOP lowering medications to control intraocular pressure
Slide 24: KSI-101 is poised to fulfill the core unmet need in MESI
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 Illustrative KSI-101 is designed to address core unmet need complications • Potent Core • Better safety IVT anti-VEGF Less • Targets both •
Slide 25: Phase 1b APEX Case Examples in MESI
Phase 1b De-Kuang Hwang APEX Case MD, PhD Examples in MESI 25
Slide 26: Phase 1b APEX study: multiple dose study of KSI-101 in MESI
Phase 1b APEX study: multiple dose study of KSI-101 in patients with MESI Weeks 0 4 8 12 16 20 24 2.5 mg Ongoing Subjects with MESI 5 mg (n~36) 10 mg KSI-101 injection End of Study A low and high dose of KSI-101 will be selected to progress into dual Phase 3 pivotal studies (PEAK and PINNACLE) in ME
Slide 27: Rapid and meaningful responses after one dose of KSI-101
After one dose of KSI-101, heterogenous MESI diseases show rapid and meaningful responses to the simultaneous IL-6 and VEGF inhibition Post-Operative Idiopathic MESI Panuveitis Intermediate Uveitis Macular Edema Day 1 Week 4 Juvenile Idiopathic Focal Chorioretinal Punctate Inner Arthritis inflammati
Slide 28: Phase 3 Program in MESI
Phase 3 Ariel Schlaen MD, PhD Program in MESI 28
Slide 29: PEAK and PINNACLE studies: efficient master protocol design
Phase 3 Peak and Pinnacle studies: efficient master protocol design A single screening process for both studies CST≥320 and BCVA 25-78 letters CST≥400 Day 1 enroll in either study CST<400 & ≥320 based on CST and BCVA BCVA 25-78 BCVA 25-70 BCVA 71-78 PEAK PINNACLE MESI with more severe disease MESI w
Slide 30: Key eligibility criteria for MESI
Key eligibility criteria for MESI PEAK Key inclusion for both • CST of ≥400 microns on SD-OCT in Study Eye • Adult patients with decrease in vision primarily resulting from MESI • BCVA ETDRS score of ≥25 and ≤70 letters in the Study Eye • Active macular leakage with • Active or inactive non-infectio
Slide 31: Phase 3 pivotal programs in MESI to be initiated mid-2025
Phase 3 pivotal programs in MESI to be initiated mid-2025: PEAK and PINNACLE Primary endpoint: change in best corrected visual acuity from baseline 31
Slide 32: Pipeline
Ariel Schlaen Pipeline MD, PhD Building on Kodiak’s Bispecific Protein Platform for Ocular Inflammatory Disease 32
Slide 33: KSI-102 and KSI-103 are being developed for ocular inflammation
KSI-102 and KSI-103 are advancing and being developed for the treatment of ocular inflammation MOA Indication/MOA Pre-clinical Pre-IND Phase 1/2 Phase 3 • GLOW1 primary endpoint met Diabetic Retinopathy • GLOW2 topline data expected Q1 2026 Anti-VEGF Antibody • DAYLIGHT primary endpoint met Tarcocim
Slide 34: Complex cytokine interactions drive chronic ocular inflammatory disease
Complex cytokine interactions drive chronic ocular inflammatory disease. TNF-ɑ, IL-6 and IL-1 levels are upregulated in these patients Aqueous Humor Dot plots comparing immune mediator levels in aqueous humor (AH) of patients with idiopathic uveitis and noninflammatory controls patients (cataract ag
Slide 35: Modeling ocular inflammation through leukocyte-endothelial adhesion
Modeling ocular inflammation through leukocyte-endothelial adhesion: roles of TNF-α, IL1-β and IL-6 Leukocyte endothelial adhesion model Adhesion Implications • All 3 cytokines are involved in driving ocular inflammation: TNFα, IL-1β and IL-6/R demonstrated leukocyte adhesion • IL-1β and TNFα have t
Slide 36: Cytokines additively compromise the blood-retinal barrier
Modeling macular edema and vascular permeability: barrier function measurements reveal cytokines additively compromise the blood-retinal barrier TNFa and IL-6 TNFa and IL-6 150 % Resistance 100 Untreated TNFα 50 IL-6/R TNFα + IL6/R 0 0 20 40 60 Hours IL-1b and IL-6 IL-1b and IL-6 150 % Resistance 10
Slide 37: KSI-102 and KSI-103: dual cytokine targeting
KSI-102 and KSI-103: Engineered to inhibit TNF-α/IL-6 and IL-1/IL-6 through dual cytokine targeting KSI-102 KSI-103 (αTNF-α / αIL-6 bispecific) (IL-1 trap / αIL-6 bispecific) αTNF-α αTNF IL-1 Trap IL-1 trap mimics native heterodimeric receptor and can bind to IL-1α or IL-1β αIL-6 αIL-6 TNF-α IL-6 IL
Slide 38: Bispecifics rescue junctional proteins and barrier integrity
Bispecifics can superiorly (i) rescue junctional proteins, (ii) normalize cell morphology, and (iii) physiological barrier integrity and may (iv) normalize effects of existing inflammation TNFa and IL-6 Inflammation Treatment UT 100 TNFα + IL-6/R + Bispecific % Resistance TNFα + IL-6/R + anti-TNFα 5
Slide 39: Panelist Discussion
Panelist Discussion KODIAK
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