Kodiak Sciences Inc · NASDAQ:KOD
Kodiak Sciences — Angiogenesis, Exudation, and Degeneration 2019
21 slides from Kodiak Sciences's conference presentation, Feb 9, 2019
Slide 1: Phase 1 First-In-Human Study of KSI-301: A Novel Anti-VEGF Antibody Biopolymer Conjugate
Phase 1 First-In-Human Study of KSI-301: A Novel Anti-VEGF Antibody Biopolymer Conjugate With Extended Durability Diana V. Do, MD Professor of Ophthalmology Byers Eye Institute, Stanford University School of Medicine Angiogenesis, Exudation, and Degeneration 2019 February 9, 2019
Slide 2: Financial Disclosures
Financial Disclosures ▪ Research Grants: – Boehringer Ingelheim – Genentech – Regeneron – Santen ▪ Advisor / Consultant: – Kodiak – Aerie – Boehringer Ingelheim – Clearside – Novartis – Regeneron – Santen 2
Slide 3: Key Points
Key Points ▪ KSI-301 is a novel Antibody Biopolymer Baseline Conjugate built on Kodiak’s ABC Platform ▪ Intravitreal KSI-301 inhibits VEGF with enhanced durability, tissue bioavailability, biocompatibility, and stability ▪ Phase 1a single ascending dose study results: – Well-tolerated at all dose le
Slide 4: Real-world outcomes emphasize the limitations of current anti-VEGF therapies
Real-world outcomes emphasize the limitations of current anti-VEGF therapies Europe1 Number of 8 injections in 6 2 years Mean change in VA Without high UK 9.0 4 intensity treatment, by country Netherlands 8.7 2 gradual VA loss 0 Germany 5.6 can begin after only 0 180 360 540 720 -2 Days France 6.3 3
Slide 5: Designer medicines to solve the real-world effectiveness problem
Designer medicines to solve the real-world effectiveness problem KSI-301 is an antibody biopolymer conjugate intended to be Same where it matters Different where it matters ▪ Clinically proven target: VEGF ▪ Designed-in ocular durability ▪ Antibody-based biologic ▪ Fast systemic clearance ▪ Intravit
Slide 6: KSI-301 bioconjugate optimizes both size and formulation strength to improve durability
KSI-301 bioconjugate optimizes both size and formulation strength to improve durability Drug/Candidate: Brolucizumab Ranibizumab Aflibercept KSI-301 Single-chain Antibody Antibody Recombinant Molecule type Antibody Biopolymer fragment fusion protein fragment Conjugate (ABC) Molecular structure Molec
Slide 7: KSI-301 bioconjugate is more potent in vitro than unconjugated anti-VEGFs
KSI-301 bioconjugate is more potent in vitro than unconjugated anti-VEGFs In vitro assays demonstrate KSI-301 bioconjugate has a deeper potency compared to bevacizumab, ranibizumab, and aflibercept because of the special nature of its phosphorylcholine biopolymer Binding affinity of Biochemical assa
Slide 8: KSI-301 bioconjugate has greater bioavailability because of its phosphorylcholine biopolymer
KSI-301 bioconjugate has greater bioavailability because of its phosphorylcholine biopolymer Ocular tissue bioavailability after single intravitreal injection Data from in vivo rabbit models Retina Choroid/RPE % of vitreous concentration % of vitreous concentration (mean ± SEM) (mean ± SEM) Days pos
Slide 9: KSI-301 bioconjugate has potential for extended durability and more flexible retreatment window
KSI-301 bioconjugate has potential for extended durability and more flexible retreatment window KSI-301 bioconjugate has a flatter (better) ocular PK curve. This translates into multi-Log concentration advantage versus other biologics. ◆ KSI-301 ◼ Aflibercept Drug Concentration (µg/mL) ⚫ Ranibizumab
Slide 10: KSI-301 Phase 1 clinical study: single ascending dose study design
KSI-301 Phase 1 clinical study: single ascending dose study design Time: Day 0 Day 1 Day 7 Wk 2 Wk 4 Wk 8 Wk 12 KSI-301 • 1.25 mg (25 μL) • 2.5 mg (50 μL) • 5 mg (100 μL) Single Primary Extended intravitreal objective: follow-up injection 2-week Safety • Eyes with diabetic macular edema (DME), one e
Slide 11: Demographic and ocular baseline characteristics
Demographic and ocular baseline characteristics Demographics, n=9 Age (years, mean) 62 Gender 7M, 2F Ocular Characteristics, Study Eye, n=9 Previously received Anti-VEGF 8/9 # of anti-VEGF treatments in last year - median (range) 3 (0, 7) Time since last anti-VEGF, days - median (range) 95 (52, >365
Slide 12: Safety outcomes: every dose level well-tolerated through 12 week follow-up period
Safety outcomes: every dose level well-tolerated through 12 week follow-up period ▪ No dose limiting toxicities ▪ No drug-related adverse events or drug-related serious adverse events ▪ No intraocular inflammation ▪ Optically clear media after each injection ▪ No anti-drug antibodies detected in any
Slide 13: Improvements in vision and retinal thickness after single-dose KSI-301 through 12 weeks
Improvements in vision and retinal thickness after single-dose KSI-301 through 12 weeks +12.5 Median change in BCVA (ETDRS Letters) +9 Rapid, high magnitude responses as early as 1 week after dosing Days Median change in OCT CST Durable improvements out to 12 weeks (microns) -120 -121 Median changes
Slide 14: Case example: resolution of macular edema sustained through 12 weeks
Case example: resolution of macular edema sustained through 12 weeks in patient with prior suboptimal response Clinical history summary (site reported): Date Treatment VA Snellen CST Baseline Retrospective 1/2018 20/40 - 4/2018 Bevacizumab 20/40 431 6/2018 Bevacizumab 20/60 655 8/2018 KSI-301 20/160
Slide 15: Case example: improvement through 12 weeks of subretinal fluid
Case example: improvement through 12 weeks of subretinal fluid in patient with extensive foveal lipid exudates Baseline Clinical history summary (site reported): Baseline VA Date Treatment Snellen 1/2018 Bevacizumab 20/60 Retrospective 3/2018 Bevacizumab 20/100 4/2018 Bevacizumab 20/150 5/2018 20/35
Slide 16: Important early development questions successfully addressed in KSI-301 Phase 1 study
Important early development questions successfully addressed in KSI-301 Phase 1 study ✓Manufacturability ✓Optical Clarity ✓Target Tissue Access ✓Safety ✓Speed of ✓Potency ✓Clinical Onset Durability 16
Slide 17: Key Takeaways
Key Takeaways ▪ KSI-301 is a novel Antibody Biopolymer Conjugate that inhibits VEGF ▪ Phase 1a single ascending dose study results: – Well-tolerated at all dose levels – Rapid-onset, high-magnitude improvements sustained to 12 weeks ▪ Objective: the “go-to drug” for induction and maintenance therapy
Slide 18: Acknowledgements
Acknowledgements ▪ Principal Investigators & Site Teams: – Sunil Patel, MD PhD – Pravin Dugel, MD – David Boyer, MD – Mark Wieland, MD – Richard McDonald, MD ▪ Kodiak Sciences: – Desiree Beutelspacher – Jason Ehrlich, MD PhD – Hong Liang, PhD – Joel Naor, MD MSc – Victor Perlroth, MD – Almas Qudrat,
Slide 19: Appendix
Appendix
Slide 20: Phase 1b open-label study in wet AMD, DME and RVO
Phase 1b open-label study in wet AMD, DME and RVO Primary Endpoint Week 0 4 8 12 16 20 24 28 32 36 KSI-301 5 or 2.5 mg wAMD DME/ DR RVO • Study now recruiting (NCT03790852) = KSI-301 injection • Open-label study to further explore KSI-301 safety, = Dosing as needed (PRN) bioactivity, durability (⁓50
Slide 21: Phase 2 study in wet AMD (US/EU)
Phase 2 study in wet AMD (US/EU) Pivotal study design, head-to-head against standard of care aflibercept Primary Endpoint AMD 0 4 8 12 16 20 24 28 32 36 40 44 48 52 KSI-301 Q20W 5 mg Q12W Q16W Q12W Q16W Aflibercept q8w 2 mg = KSI-301 injection • All patients ≥Q12W with KSI-301 = Aflibercept injectio
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