Kodiak Sciences Inc · NASDAQ:KOD
Kodiak Sciences — Angiogenesis, Exudation, and Degeneration 2024
21 slides from Kodiak Sciences's conference presentation, Feb 3, 2024
Slide 1: KSI-501 Bispecific Anti-VEGF Anti-IL-6 Antibody Biopolymer Conjugate: First Time Phase 1 MAD Results
KSI-501 Bispecific Anti-VEGF Anti-IL-6 Antibody Biopolymer Conjugate: First Time Results of the Multiple Ascending Dose Phase 1 Study Mark Barakat, M.D. Retina Macula Institute of Arizona Angiogenesis, Exudation, and Degeneration 2024 February 3, 2024 1
Slide 2: Disclosures
Disclosures • Presenter’s Financial Disclosures: ‒ Kodiak (C, R) • This presentation will discuss IRB/IEC approved research of an investigational medicine. (C): Consultant; (S): Stock/shareholder; (R): Grants/Research Support 2
Slide 3: Substantial patient-to-patient variability is the norm with anti-VEGF monotherapy
Substantial patient-to-patient variability is the norm for patients treated with anti-VEGF monotherapy BCVA change from baseline during year 1 for OCT CST change from baseline during year 1 for individual patients treated with Q8W aflibercept individual patients treated with Q8W aflibercept OCT CST
Slide 4: IL-6 plays an important role in retinal vascular and hyperpermeability disorders
IL-6 plays an important role in the pathophysiology of retinal vascular and hyperpermeability disorders • IL-6 is a pro-inflammatory cytokine and IL-6 Pathway immune growth factor implicated in the pathophysiology of multiple retinal diseases IL-6 Rα gp130 and is associated with poor anti-VEGF treat
Slide 5: KSI-501 is a first-in-class bispecific inhibiting IL-6 and VEGF
KSI-501 is a first-in-class bispecific that inhibits two powerful pathophysiologic mechanisms in retinal disease – IL-6 and VEGF VEGF Pathway IL-6 Pathway VEGFR IL-6 Rα gp130 Endothelial Endothelial Endothelial Endothelial Vascular Survival Proliferation Migration Activation Hypertrophy Vascular End
Slide 6: KSI-501 bispecific protein design enables efficient binding to both IL-6 and VEGF
KSI-501 bispecific protein features a unique design that enables highly efficient binding to both IL-6 and VEGF “Two hands on the ball” VEGF Trap BEST-IN-CLASS VEGF INHIBITION BINDING CAPACITY OF The VEGF trap mimics the native UP TO 3 MOLECULES receptor and binds multiple targets This first in clas
Slide 7: ABC platform gives KSI-501ABC increased molecular size and extended ocular half-life
By leveraging the Antibody Biopolymer Conjugate (ABC) platform KSI-501ABC has an increased molecular size, and in turn an extended ocular half-life + = BISPECIFIC BIOPOLYMER CONJUGATE Immunologically inert lgG1 Branched, Optically Clear, anti-IL-6 Antibody High Molecular Weight + VEGF Trap Phosphory
Slide 8: Electron microscopy images illustrate real time activation of the anti-VEGF trap
Negative-stain electron microscopy images of KSI-501ABC illustrate real time activation of the anti-VEGF trap in the presence of VEGF KSI-501ABC KSI-501ABC + VEGF VEGF anti-IL6 VEGF Trap Fab anti-IL6 Fab Fc Fc Biopolymer Biopolymer In the absence of VEGF, VEGF Upon VEGF binding, VEGF trap trap arms
Slide 9: KSI-501 shows comparable VEGF affinity to aflibercept and IL-6 potency to vamikibart
KSI-501 demonstrates comparable VEGF binding affinity and potency to aflibercept and comparable IL-6 potency as vamikibart Key disease drivers in Aflibercept Vamikibart (anti-IL-6 mAb) KSI-501^ retinal diseases Inflammation Angiogenesis Barrier function Vascular leakage Preclinical potency Binding a
Slide 10: KSI-501 inhibits angiogenesis and normalizes blood retinal barriers
KSI-501 inhibits angiogenesis and normalizes the inner and outer blood retinal barriers • Inner blood-retinal barrier: leakage from vascular endothelium disruption leads to macular edema and hemorrhage1 • Outer blood-retinal barrier: RPE integrity prevents choroidal vascularization from invading the
Slide 11: Dual inhibition confers superior normalization versus monotherapy
Dual inhibition of VEGF and IL-6 by KSI-501 confers superior normalization of complex biologies compared to either anti-VEGF or anti-IL-6 monotherapy alone Exogenous VEGF and IL-6 Normal tight junction disruption and changes in cell morphology Monotherapy Inhibition Dual inhibition No Inhibitors Ant
Slide 12: Dual inhibition offers opportunity across a range of retina disease indications
Dual inhibition of IL-6 and VEGF can provide ample opportunity for clinical use of KSI-501 across a range of retina disease indications • Preclinical and clinical data support the role of IL-6 as a key inflammatory modulator in retinal vascular diseases and seems to be related to the potential respo
Slide 13: KSI-501ABC Phase 1 Study First Time Results
KSI-501ABC Phase 1 Study First Time Results 13
Slide 14: KSI-501ABC Phase 1 multiple ascending dose study in diabetic macular edema
KSI-501ABC Phase 1 multiple ascending dose study in patients with diabetic macular edema 5 mg Primary Endpoint: (100 ml) Ocular and systemic safety at Week 24 3.75 mg (75 ml) 2.5 mg (50 ml) 1.25 mg (25 ml) KSI-501 dose Study design Key Inclusion/Exclusion Criteria • Multiple ascending dose design •
Slide 15: Demographics and baseline characteristics were typical of DME patients
Demographics, general characteristics and baseline ocular characteristics were typical of DME patients KSI-501ABC n=16 Age, years, mean (SD) 67.3 (7.4) Female, n (%) 6 (37.5) Hemoglobin A1c, % (SD) 7.2 (1.2) Diabetes Type 2, n (%) 14 (87.5%) DME disease duration, months, mean (SD) 38.3 (40.4) BCVA,
Slide 16: Treatment naïve patients had robust visual and anatomical gains
In treatment naïve patients, dosing with KSI-501ABC resulted in robust visual and anatomical gains that were sustained over 16 weeks after the last dose Mean Change in BCVA (n=7) 15 10 5 0 0 4 8 12 16 20 24 Mean Change in OCT CST (n=7) 0 -50 -100 -150 0 4 8 12 16 20 24 16
Slide 17: Previously treated patients had anatomical improvement and sustained BCVA gains
In previously treated population, dosing with KSI-501ABC resulted in anatomical improvement, as well as meaningful and sustained gains in BCVA Mean Change in BCVA (n=9) 10 5 0 0 4 8 12 16 20 24 Mean Change in OCT CST (n=9) 50 0 -50 0 4 8 12 16 20 24 17
Slide 18: Meaningful BCVA increase for the majority of patients
Treatment with KSI-501ABC resulted in a meaningful increase of BCVA for the majority of patients during the study 100% Proportion of patients with 2- and 3-line BCVA improvement at any time during the study, in at least 2 separate visits 75% 71.4% 66.7% Treatment naïve (n=7) Previously treated (n=9)
Slide 19: KSI-501ABC was safe and well tolerated
KSI-501ABC was safe and well tolerated KSI-501ABC Adverse Events (AEs) in the Study Eye N=16 Summary, n (%) Subjects with ≥1 AEs 7 (43.8) Treatment-related AEs 1 (6.3) Serious AEs 0 Treatment-related serious AEs 0 Severe AEs 0 AEs leading to study discontinuation 0 AEs in the Study Eye, n (%) Intrao
Slide 20: KSI-501 developed in parallel as naked protein and as bioconjugate
The KSI-501 program will be developed in parallel as a “naked” protein and as a bioconjugate, addressing two very different unmet needs KSI-501P KSI-501ABC Unconjugated Protein Antibody Biopolymer Conjugate There are no available intravitreal biologic therapies addressing the spectrum of Addressing
Slide 21: Summary
Summary The pathophysiology of retinal vascular and hyperpermeability disorders is multifactorial Retinal diseases and multiple cytokines beyond VEGF are thought to be involved. multifactorial etiology • IL-6 and VEGF are key mediators of inflammation, hyperpermeability and angiogenesis. • Repeated
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