Kodiak Sciences Inc · NASDAQ:KOD
Kodiak Sciences — AAO Annual Meeting – Retina Subspecialty Day 2019
29 slides from Kodiak Sciences's conference presentation, Oct 11, 2019
Slide 1: Extended Durability in Exudative Retinal Diseases Using KSI-301
Extended Durability in Exudative Retinal Diseases Using the Novel Intravitreal Anti-VEGF Antibody Biopolymer Conjugate KSI-301 First-time Results from a Phase 1b Study in Patients with wAMD, DME and RVO Charles C. Wykoff, MD, PhD Retina Consultants of Houston Houston, TX AAO Annual Meeting – Retina
Slide 2: Disclosures
Disclosures ▪ Financial: Adverum (C, R); Aerpio (C, R); Alimera Sciences (C); Allegro (C); Allergan (C, R); Apellis (C, R); Bayer (C); Clearside Biomedical (C, R); Chengdu Kanghong (R); DORC (C); EyePoint (C); Fosun (C); Genentech/Roche (C, R); Iveric Bio (formerly Ophthotech) (C, R); Kodiak Science
Slide 3: Investigational Treatments for Exudative Retinal Diseases
Investigational Treatments for Exudative Retinal Diseases aimed at improving efficacy & durability Aflibercept Bevacizumab Ranibizumab Brolucizumab Abicipar Faricimab PDS Dexamethasone Triamcinolone Sunitinib KSI-301 Conbercept OPT-302 Fluocinolone acetonide AAV.7m8 ADVM-022 RGX-314 3
Slide 4: Antibody Biopolymer Conjugates (ABC) biologics engineered for increased durability and efficacy
Antibody Biopolymer Conjugates (ABC) biologics engineered for increased durability and efficacy Single Site-Specific + Stable = (Covalent) Linkage ANTIBODY BIOPOLYMER IgG1 Antibody Branched Inert Immune High Molecular Weight Effector Function Optically Clear Phosphorylcholine Polymer ANTIBODY BIOPOL
Slide 5: Go Bigger to Last Longer
Go Bigger to Last Longer KSI-301: ABC designed to block all VEGF-A Isoforms Brolucizumab Ranibizumab Bevacizumab Aflibercept KSI-301 Single-chain Antibody Recombinant Antibody Biopolymer Molecule type antibody Antibody fragment fusion protein Conjugate (ABC) fragment Molecular structure Molecular we
Slide 6: Properties: Preclinical Data
KSI-301 Properties: Preclinical Data Special features from the ultra-hydrophilic phosphorylcholine biopolymer Remarkable Intraocular Excellent Retinal Fast Systemic Durability1 Bioavailability2 Clearance3 KSI-301 half-life (rabbit) Plasma concentration 10,000.000 • 10.5 days retina Retina 50 after 0
Slide 7: Clinical Data
KSI-301 Clinical Data 113 patients dosed to date
Slide 8: Phase 1a
KSI-301 Phase 1a well-tolerated with rapid anatomic & visual response Median change in BCVA +12.5 (ETDRS Letters) • Diabetic macular edema (DME) patients with +9 severe disease (n=9) • Incompletely responsive to previous anti-VEGF treatment (8/9 previously treated) (median 3, range 0-7 in the year p
Slide 9: Phase 1b: insight into durability among treatment naïve subjects
KSI-301 Phase 1b insight into durability among treatment naïve subjects Randomized, open label study to evaluate multidose safety, efficacy & durability (n=105) wAMD (n=35) DME (n=35) RVO (n=35) Randomized 1:3 KSI-301 2.5 mg (50 mL) KSI-301 5 mg (100 mL) Loading Phase Durability Assessment Phase Wee
Slide 10: Phase 1b Retreatment Criteria
KSI-301 Phase 1b Retreatment Criteria prespecified by disease state ▪ wAMD – Increase in CST ≥75 µm with a decrease in BCVA of ≥ 5 letters compared to Week 12, OR – Decrease in BCVA of > 5 letters compared to Day 1, due to worsening wAMD activity, OR – Decrease in BCVA of ≥ 10 letters compared to th
Slide 11: Phase 1b Baseline Characteristics
KSI-301 Phase 1b Baseline Characteristics wAMD Cohort DME Cohort RVO Cohort Variable (n=35) (n=34) (n=35) Age, mean (SD), years 77.2 (11.0) 60.7 (10.4) 63.6 (12.6) Gender, n (%), female 25 (71.4) 13 (38.2) 13 (37.1) Race, n (%), White 32 (91.4) 28 (82.4) 31 (88.6) BCVA, mean (SD), ETDRS letters 64.5
Slide 12: Phase 1b First Time Results
KSI-301 Phase 1b First Time Results
Slide 13: Efficacy of KSI-301 in Wet AMD
Efficacy of KSI-301 in Wet AMD change from baseline to week 16 in mean BCVA & OCT 75 ETDRS letters 70 +5.4 BCVA 65 60 0 4 8 Weeks 12 16 450 400 OCT CST microns 350 -72 300 250 Patients reaching Week 16 Interim data. Includes only randomized patients that reached Week 16 visit by the data cutoff date
Slide 14: KSI-301 in wAMD: Durability Assessment
KSI-301 in wAMD: Durability Assessment Emerging data support 3 to 5+ month durability Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 35 (n=7) 7 1 3 5 KSI-301 7 5 mg 9 11 (n=20) 13 15 17 Total 19 (n=27) Durability Phase (months): 1
Slide 15: KSI-301 in wAMD: Durability Assessment
KSI-301 in wAMD: Durability Assessment Emerging data support 3 to 5+ month durability Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 35 (n=7) 7 1 3 5 KSI-301 7 5 mg 9 11 (n=20) 13 15 17 Total 19 (n=27) Durability Phase (months): 1
Slide 16: KSI-301 in wAMD: Durability Assessment
KSI-301 in wAMD: Durability Assessment Emerging data support 3 to 5+ month durability Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 35 (n=7) 7 1 3 5 KSI-301 7 5 mg 9 11 (n=20) 13 80% (12/15) reach 4 months or 15 17 longer until fi
Slide 17: Efficacy of KSI-301 in DME
Efficacy of KSI-301 in DME change from baseline to week 16 in mean BCVA & OCT 85 ETDRS letters 80 +8.4 BCVA 75 70 65 0 4 8 Weeks 12 16 500 450 OCT CST microns 400 350 300 -140 250 Patients reaching Week 16 Interim data. Includes only randomized patients that reached Week 16 visit by the data cutoff
Slide 18: KSI-301 in DME: loading doses can provide sustained disease control
KSI-301 in DME: 3 loading doses can provide sustained disease control of 3 months or longer Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 23 (n=4) 4 1 2 3 4 KSI-301 5 6 5 mg 7 8 (n=13) 9 10 11 12 Total 13 (n=17) Durability Phase (
Slide 19: KSI-301 in DME: loading doses can provide sustained disease control
KSI-301 in DME: 3 loading doses can provide sustained disease control of 3 months or longer Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 23 (n=4) 4 1 2 3 4 KSI-301 5 6 5 mg 7 8 (n=13) 9 10 11 12 Total 13 (n=17) Durability Phase (
Slide 20: KSI-301 in DME: loading doses can provide sustained disease control
KSI-301 in DME: 3 loading doses can provide sustained disease control of 3 months or longer Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 23 (n=4) 4 1 2 3 4 KSI-301 5 6 5 mg 7 8 Some patients reaching 4, 5, even (n=13) 9 6 months
Slide 21: in DR: signs of disease modification seen within weeks
KSI-301 in DR: signs of disease modification seen within 12 weeks DRSS Score (n=15) DAY 1 WEEK 22 100 PDR (DRSS 65) NPDR (DRSS 53) 90 80 Case Example 35 % of patients 70 60 43 KSI-301 47 50 53 5 mg 40 61 65 30 71 20 75 10 3 loading 0 doses & no Baseline Week 12 re-treatment for 14 • All patients hav
Slide 22: Efficacy of KSI-301 in RVO
Efficacy of KSI-301 in RVO change from baseline to week 16 in mean BCVA & OCT 80 75 ETDRS letters +21.3 70 BCVA 65 60 55 50 45 0 4 8 Weeks 12 16 850 750 OCT CST 650 microns 550 450 350 -353 250 Interim data. Includes only randomized patients that reached Week 16 visit by the data cutoff date of 10 O
Slide 23: KSI-301 in RVO: emerging durability data
KSI-301 in RVO: emerging durability data show potential for 2 to 3 month or longer dosing Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 3 5 (n=6) 1 3 KSI-301 5 7 5 mg 9 (n=18) 11 13 15 Total 17 (n=24) Durability Phase (months): 1
Slide 24: KSI-301 in RVO: emerging durability data
KSI-301 in RVO: emerging durability data show potential for 2 to 3 month or longer dosing Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 3 5 (n=6) 1 3 KSI-301 5 7 5 mg 9 (n=18) 11 13 15 Total 17 (n=24) Durability Phase (months): 1
Slide 25: KSI-301 in RVO: emerging durability data
KSI-301 in RVO: emerging durability data show potential for 2 to 3 month or longer dosing Loading Phase Durability Assessment Phase Overall Time on Study (weeks) 0 4 8 12 16 20 24 28 32 36 KSI-301 1 2.5 mg 3 5 (n=6) 1 3 KSI-301 5 7 5 mg 9 Only 3 patients have received (n=18) 11 13 >1 retreatment, ea
Slide 26: Safety of KSI-301: multiple-dose exposure is well-tolerated
Safety of KSI-301: multiple-dose exposure is well-tolerated with no intraocular inflammation 113 316 Subjects dosed Total doses given 104 99 86 At Day 1 At Week 4 At Week 8 in Phase 1a+1b in Phase 1a+1b Phase 1b subjects with # of loading doses received ▪ No intraocular inflammation or ocular SAEs i
Slide 27: Now Recruiting: Pivotal Phase 2 DAZZLE Study
Now Recruiting: Pivotal Phase 2 DAZZLE Study Dosing with KSI-301 in wet AMD as infrequently as every 20 weeks • ⁓400 treatment naïve Matched Phase Disease Activity Durability Assessments Primary endpoint wAMD patients • Randomized study vs Week 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aflibercept Q20W
Slide 28: Conclusion: KSI-301 is Demonstrating Promising Safety, Efficacy and Durability
Conclusion: KSI-301 is Demonstrating Promising Safety, Efficacy and Durability ▪ Antibody Biopolymer Conjugates (ABCs) are a new design platform for long durability intravitreal medicines ▪ KSI-301 (anti-VEGF ABC) has achieved important development milestones – Excellent Safety: zero cases of intrao
Slide 29: Acknowledgements
Acknowledgements Principal Investigators Kodiak Sciences ▪ Mark Barakat, MD ▪ Pablo Velazquez-Martin, MD ▪ Brian Berger, MD ▪ Desiree Beutelspacher ▪ David Boyer, MD ▪ Amy Duguay, BS ▪ David Brown, MD ▪ Hong Liang, PhD ▪ Pravin Dugel, MD ▪ Bryce Miller, MPA ▪ David Eichenbaum, MD ▪ Joel Naor, MD MSc
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