Kodiak Sciences Inc · NASDAQ:KOD
Kodiak Sciences — Retina Society Annual Meeting 2019
19 slides from Kodiak Sciences's conference presentation, Sep 15, 2019
Slide 1: Novel Anti-VEGF Antibody Biopolymer Conjugate KSI-301 with Potential for Extended Durability
Novel Anti-VEGF Antibody Biopolymer Conjugate KSI-301 with Potential for Extended Durability in Retinal Vascular Diseases Late-Breaking Results from a Phase 1b Study in Patients with wAMD, DME and RVO David M. Brown, MD, FACS Retina Consultants of Houston Houston, TX Retina Society Annual Meeting Se
Slide 2: Relevant Financial Disclosures
Relevant Financial Disclosures ▪ Alcon/Novartis (RG,C) ▪ Allergan (RG,E,C) ▪ Genentech/Hoffmann-La Roche (RG,C) ▪ Graybug Vision (RG,C) ▪ Kanghong Pharma (RG,C) ▪ Kodiak Sciences (RG,C) ▪ Regeneron/Bayer (RG,C) ▪ Samsung Bioepsis (RG,C) RG- Research Grant to Institution E= Equity/ Options C: Consult
Slide 3: Key Points
Key Points ▪ ABCs (Antibody Biopolymer Conjugates): a new scientific approach and design platform for intravitreal drugs ▪ KSI-301 (Kodiak Sciences) initial data: early efficacy and safety in major retinal vascular diseases ▪ Emerging wAMD durability data from Phase 1b support Phase 2 study design w
Slide 4: ABCs are a new scientific design platform for extended durability intravitreal therapeutics
ABCs are a new scientific design platform for extended durability intravitreal therapeutics ABC PLATFORM CHARACTERISTICS OF KSI-301 Molecular weight 950 kDa + Stable = Clinical dose 5 mg (by weight of antibody) linkage Equivalent molar dose (compared to ranibizumab) 7x ANTIBODY BIOPOLYMER CONJUGATE
Slide 5: ABCs have improved ocular PK plus other unique features due to the phosphorylcholine biopolymer
ABCs have improved ocular PK plus other unique features due to the phosphorylcholine biopolymer SPECIAL FEATURES OF ABCs DUE TO ABC ANTI-VEGF PK CURVE1 PHOSPHORYLCHOLINE BIOPOLYMER2 10,000.000 • Better tissue bioavailability ◆ KSI-301 1,000.000 ~8x greater than aflibercept DRUG CONCENTRATION ◼ Aflib
Slide 6: Clinical Proof of Concept Study of KSI-301
Clinical Proof of Concept Study of KSI-301 Phase 1b, open-label, randomized study ▪ Key questions in early development of KSI-301 and the ABC Platform: – Multiple-dose safety – Bioactivity in VEGF-driven diseases: wAMD, DME, RVO – Durability ▪ Study design: – Anti-VEGF treatment-naïve patients, BCVA
Slide 7: KSI-301 Phase 1b Baseline Characteristics
KSI-301 Phase 1b Baseline Characteristics wAMD Cohort DME Cohort RVO Cohort Variable (n=35) (n=27) (n=35) Age (years, median) 76 60 64 Gender (Female, %) 71.4 40.7 37.1 BCVA (ETDRS letters, median) 66 70 59 OCT CST (microns, median) 380 402 630 Includes all patients randomized as of 6 September 2019
Slide 8: KSI-301 Phase 1b Results
KSI-301 Phase 1b Results
Slide 9: Efficacy of KSI-301 in Wet AMD
Efficacy of KSI-301 in Wet AMD Change from Baseline to Week 12 in median BCVA and OCT CST 80 Direct reduction in size and vascular flow rate of the choroidal neovascularization, effectively eliminating subretinal fluid +8 ETDRS letters 75 BCVA 70 DAY 1 65 60 0 4 Weeks 8 12 450 400 OCT CST microns WE
Slide 10: Efficacy of KSI-301 in DME
Efficacy of KSI-301 in DME Change from Baseline to Week 12 in median BCVA and OCT CST 85 Rapid DME resolution seen as early as 1 week after +9 the initial dose, sustained to Week 12 ETDRS letters 80 BCVA 75 DAY 1 70 65 0 4 Weeks 8 12 450 OCT WEEK 1 400 OCT CST microns 350 300 -120 WEEK 12 250 n=11 I
Slide 11: Improvement in diabetic retinopathy status
Improvement in diabetic retinopathy status Case Example of KSI-301 5 mg in DR DAY 1 WEEK 12 WEEK 22 Proliferative DR (DRSS 65) Non-Proliferative DR (DRSS 53) Non-Proliferative DR (DRSS 53) KSI-301 No 5 mg additional 3 loading doses doses Conversion from PDR to NPDR Fast and substantial (2-step) impr
Slide 12: Efficacy of KSI-301 in Retinal Vein Occlusion
Efficacy of KSI-301 in Retinal Vein Occlusion Change from Baseline to Week 12 in median BCVA and OCT CST 85 Rapid edema resolution seen as early as 1 week 80 +23.5 after the initial dose, sustained to Week 12 ETDRS letters 75 BCVA 70 65 DAY 1 60 55 50 0 4 Weeks 8 12 700 OCT 650 WEEK 1 600 OCT CST 55
Slide 13: Multiple-dose exposure to KSI-301 is well-tolerated with no intraocular inflammation in 257 doses
Multiple-dose exposure to KSI-301 is well-tolerated with no intraocular inflammation in 257 doses 97 257 Subjects dosed Total doses 97 87 65 At Day 1 At Week 4 At Week 8 in Phase 1b in Phase 1b Subjects with # of loading doses received ▪ No intraocular inflammation or ocular SAEs reported to date ▪
Slide 14: KSI-301 Phase 1b Durability Assessment Retreatment Criteria
KSI-301 Phase 1b Durability Assessment Retreatment Criteria ▪ Retreatment criteria for wAMD subjects during the durability assessment phase: – Increase in OCT central subfield retinal thickness (CST) ≥75 µm with a decrease in BCVA of ≥ 5 letters compared to Week 12, OR – Decrease in BCVA of > 5 lett
Slide 15: Dosing with KSI-301 in wAMD at a minimum interval of 12 weeks
Dosing with KSI-301 in wAMD at a minimum interval of 12 weeks is supported by Phase 1b emerging data Loading Phase Durability Assessment Retreatment Time (weeks) • 1/25 patients has been 0 4 8 12 16 20 24 28 32 1 2 KSI-301 3 retreated so far 4 2.5 mg • The single retreatment 5 6 7 1 2 occurred in th
Slide 16: Is it possible to go 16 Weeks after the last dose?
Is it possible to go 16 Weeks after the last dose? Example of KSI-301 5 mg in Wet AMD DAY 1 50 letters WEEK 1 +2 letters Rapid drying effect seen at Week 1, and sustained through Week 24 without any additional doses needed WEEK 12 +8 letters WEEK 24 +11 letters OCT= optical coherence tomography OCT
Slide 17: Next Step: Phase 2 DAZZLE Study in Wet AMD
Next Step: Phase 2 DAZZLE Study in Wet AMD Disease Activity Primary • Pivotal study design, Matched Phase Durability Assessments endpoint head-to-head against Week 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aflibercept • US & EU study sites KSI-301 5 mg Q20W • ⁓400 treatment naïve Q12W Q12W wAMD patient
Slide 18: KSI-301 and ABC Platform Development Goals Achieved
KSI-301 and ABC Platform Development Goals Achieved ▪ Safety: ✓ No inflammation observed (266 total doses/106 subjects - Phase 1a/1b) ▪ Efficacy: ✓ Function (BCVA) and retinal anatomy (OCT) demonstrate potent anti-VEGF effect ▪ Durability: ✓ Encouraging durability data: 10/10 5-mg eyes extended long
Slide 19: Acknowledgements
Acknowledgements Principal Investigators: Kodiak Sciences: ▪ Sunil Patel, MD, PhD ▪ Pablo Velazquez-Martin, MD ▪ Arshad Khanani, MD ▪ Bryce Miller, MPA ▪ Mark Barakat, MD ▪ Desiree Beutelspacher ▪ Pravin Dugel, MD ▪ Amy Duguay, BS ▪ David Boyer, MD ▪ Hong Liang, PhD ▪ Mark Wieland, MD ▪ Joel Naor, M