Slide 1: Extended durability in exudative retinal diseases using a new class of molecules: KSI-301
Extended durability in exudative retinal diseases using a new class of molecules: novel anti-VEGF antibody biopolymer conjugate KSI-301 First-time results of the phase 1b study in patients with wAMD, DME and RVO Pravin U. Dugel, MD Clinical Professor Department of Ophthalmology Managing Partner Rosk
Slide 2: Relevant Financial Disclosures
Relevant Financial Disclosures Consultant to Kodiak Sciences 2
Slide 3: Key Points
Key Points Antibody Biopolymer Conjugates are a new scientific approach and design platform for intravitreal drugs KSI-301 (Kodiak Sciences) has achieved its early development goals of demonstrating strong efficacy and excellent safety in the major retinal vascular diseases Current data warran
Slide 4: There is a substantial unmet need for increased durability and efficacy
There is a substantial unmet need for increased durability and efficacy U.S. EMR Data1 Europe AURA Study2 4 5 MEAN CHANGE IN VA (LOCF) 3 MEAN CHANGE IN VA 4 2 1.52 1.01 1 3 1.24 +2.4 0.71 -0.19 0 2 -1 -0.3 -2 1 Ranibizumab n=3,350 Ranibizumab n=2,227 +0.6 -3 Aflibercept n=4,300 0 0 180 360 540 720 -
Slide 5: Antibody Biopolymer Conjugates (ABC) are designed for increased durability and efficacy
Antibody Biopolymer Conjugates (ABC) are designed for increased durability and efficacy ABC PLATFORM SCIENTIFIC DESIGN OBJECTIVES SAME WHERE IT MATTERS • Clinically proven targets • Antibody-based biologic • Intravitreal: safest method of administration + Stable = • Optically clear, no residues • Fa
Slide 6: Go Big, Not Small
Go Big, Not Small The high molecular weight of KSI-301 can provide an important dosing advantage Drug/Candidate: BROLUCIZUMAB RANIBIZUMAB AFLIBERCEPT KSI-301 Anti-VEGF ABC Single-chain Antibody Recombinant Antibody Biopolymer Molecule type antibody fragment fragment fusion protein Conjugate (ABC) Mo
Slide 7: ABCs are more than the sum of their parts
ABCs are more than the sum of their parts Special features from the phosphorylcholine biopolymer ABCS HAVE THE OPTIMAL OCULAR SPECIAL FEATURES OF ABCs DUE TO ANTI-VEGF PK CURVE1 PHOSPHORYLCHOLINE BIOPOLYMER2 10,000.000 • Better tissue bioavailability KSI-301 1,000.000 ~8x greater than aflibercept
Slide 8: Deeper potency
Deeper potency Special features from the phosphorylcholine biopolymer KSI-301 bioconjugate has a deeper potency compared to ranibizumab, aflibercept and bevacizumab, as well as its unconjugated starting protein BIOCHEMICAL ASSAY PRIMARY HUMAN RETINAL CELL-BASED ASSAY Anti-VEGF Inhibition Anti-VEGF I
Slide 9: Enhanced tissue bioavailability
Enhanced tissue bioavailability Special features from the phosphorylcholine biopolymer RETINA CHOROID/RPE • Ocular tissue bioavailability 100 100 % OF VITREOUS CONCENTRATION % OF VITREOUS CONCENTRATION after single intravitreal KSI-301 KSI-301 injection 80 Aflibercept 80 Aflibercept (MEAN ± SEM) (ME
Slide 10: KSI-301 Clinical data
KSI-301 Clinical data
Slide 11: KSI-301 demonstrated an excellent safety profile and bioactivity in first-in-human Phase 1a
KSI-301 demonstrated an excellent safety profile and bioactivity in first-in-human Phase 1a Median change in BCVA +12.5 • Diabetic macular edema (DME) patients with (ETDRS Letters) severe disease (n=9) +9 • Previously treated with limited to no response despite multiple prior anti-VEGF treatments an
Slide 12: 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 Study design: – Anti-VEGF treatment-naïve patients, BCVA ~20/25 - 20/
Slide 13: KSI-301 Phase 1b Baseline Characteristics
KSI-301 Phase 1b Baseline Characteristics wAMD Cohort DME Cohort RVO Cohort Variable (n=35) (n=25) (n=35) Age (years, median) 76 60 64 Gender (Female, %) 71.4 40 37.1 BCVA (ETDRS letters, median) 66 70 59 OCT CST (microns, median) 380 402 630 Includes all patients randomized as of 30 Aug 2019 13
Slide 14: 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 15: Efficacy of KSI-301 in DME and DR
Efficacy of KSI-301 in DME and DR Change from Baseline to Week 12 in median BCVA and OCT CST 85 Rapid DME resolution +9 seen as early as 1 week after the initial dose ETDRS letters 80 OCT BCVA 75 DAY 1 WEEK 1 70 Diabetic Retinopathy Severity Improvement 65 Conversion of PDR to NPDR with a (2-step) i
Slide 16: 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 Case Example of KSI-301 5 mg in RVO 80 +23.5 OCT-Angiography DVC OCT ETDRS letters 75 BCVA 70 65 DAY 1 60 55 50 0 4 Weeks 8 12 700 WEEK 1 650 600 OCT CST 550 microns 500 450 400 -346 WEEK 4 35
Slide 17: Multiple-dose exposure to KSI-301 is well-tolerated with no intraocular inflammation in 248 doses
Multiple-dose exposure to KSI-301 is well-tolerated with no intraocular inflammation in 248 doses 95 248 Subjects dosed Total doses 95 82 63 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 18: KSI-301 and ABC Platform Development Goals Achieved
KSI-301 and ABC Platform Development Goals Achieved Safety: ✓ Both single and multiple sequential doses of KSI-301 are well-tolerated to date ✓ No intraocular inflammation observed in 257 total doses in 104 subjects (Phase 1a + 1b) Efficacy: ✓ Rapid-onset, high magnitude improvements in both fun
Slide 19: Phase 2 DAZZLE Study in Wet AMD
Phase 2 DAZZLE Study in Wet AMD Dosing with KSI-301 as infrequently as every 20 weeks 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 •
Slide 20: Developing a Pipeline of ABCs for Retinal Disease
Developing a Pipeline of ABCs for Retinal Disease Monoclonal and Bispecific ABCs Triplet inhibitors that merge biologics with small molecules MONOSPECIFIC ABC BISPECIFIC ABC TRIPLET ABC 1 Molecule, 1 Target 1 Molecule, 2 Targets 1 Molecule, 3 Targets Monoclonal antibody conjugated to Bispecific anti
Slide 21: Key Points
Key Points Antibody Biopolymer Conjugates are a new scientific approach and design platform for intravitreal drugs KSI-301 (Kodiak Sciences) has achieved its early development goals of demonstrating strong efficacy and excellent safety in the major retinal vascular diseases Current data warran
Slide 22: 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 David Brown, MD Amy Duguay, BS David Boyer, MD Hong Liang, PhD Mark Wieland, MD Joel Naor, MD