Kodiak Sciences Inc · NASDAQ:KOD
Kodiak Sciences — 41st Annual Scientific Meeting of the American Society of Retina Specialists (July 2023)
23 slides from Kodiak Sciences's conference presentation, Jul 30, 2023
Slide 1: KSI-301 Anti-VEGF Antibody Biopolymer Conjugate for Diabetic Macular Edema
KSI-301 Anti-VEGF Antibody Biopolymer Conjugate for Diabetic Macular Edema: Primary Endpoint Efficacy and Safety Outcomes of the GLEAM and GLIMMER Phase 3 Pivotal Studies Charles C. Wykoff, M.D., Ph.D. Deputy Chair of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital Director of Resea
Slide 2: Disclosures
Disclosures This presentation will discuss IRB/IEC approved research of an investigational medicine. Charles Wykoff has the following financial interests or relationships to disclose: 4DMT (C, R), Abbvie (C), Adverum (C,R), Aerie (C), AffaMed (R), AGTC (C), Alcon (C), Alexion (R), Alimera (R), Allge
Slide 3: KSI-301 (tarcocimab tedromer) and Antibody Biopolymer Conjugates (ABCs)
KSI-301 (tarcocimab tedromer) and Antibody Biopolymer Conjugates (ABCs) + = ANTIBODY BIOPOLYMER CONJUGATE lgG1 Anti-VEGF Antibody Branched, Optically Clear, High Molecular Weight Phosphorylcholine Polymer KSI-301 (tarcocimab tedromer) is an anti-VEGF ABC that blocks all VEGF-A isoforms 3
Slide 4: GLEAM and GLIMMER – identically-designed Phase 3 studies
GLEAM and GLIMMER – identically-designed Phase 3 studies Two identically-designed, randomized, double-masked, multi-center Phase 3 non-inferiority studies of tarcocimab tedromer 5 mg vs aflibercept 2 mg in treatment-naïve DME Tarcocimab individualized dosing Aflibercept dosed every 2 to 6 months eve
Slide 5: Tarcocimab individualized dosing based on patient-specific disease activity assessments
Tarcocimab individualized dosing based on patient-specific disease activity assessments, allowing for dynamic interval adjustments between Q8 and Q24 week dosing 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Loading Doses Individualized Treatment Matched Phase Interval Determination Phase Maintena
Slide 6: Baseline ocular characteristics well-matched between groups in each study
Baseline ocular characteristics well-matched between groups in each study and between studies, and typical of treatment-naïve DME patients GLEAM GLIMMER Tarcocimab Aflibercept Tarcocimab Aflibercept Q8W-Q24W Q8W Q8W-Q24W Q8W n=230 n=230 n=229 n=228 BCVA, ETDRS Letters, mean (SD) 66.4 (9.78) 66.6 (9.
Slide 7: Patient disposition
Patient disposition GLEAM GLIMMER Tarcocimab Aflibercept Tarcocimab Aflibercept Q8W-Q24W Q8W Q8W-Q24W Q8W n=230 n=230 n=231 n=228 Patients treated 230 (100%) 230 (100%) 229 (99.1%) 228 (100%) Patients completing Week 64 204 (88.7%) 211 (91.7%) 210 (90.9%) 204 (89.5%) Discontinuations prior to Week 6
Slide 8: Primary endpoint: mean change in BCVA from baseline
Primary endpoint: mean change in BCVA from baseline at average of weeks 60-64. Tarcocimab did not demonstrate non-inferiority to aflibercept in either GLEAM or GLIMMER GLEAM: Mean Change in BCVA from Baseline 20 Aflibercept Q8W Tarcocimab Q8W-Q24W ETDRS Letters Avg of Weeks 60 & 64 15 (SD) 10 10.3 (
Slide 9: Durability: ≥50% of tarcocimab patients consistently achieved 6-month dosing
Durability: ≥50% of tarcocimab patients consistently achieved 6-month dosing Three in every 4 tarcocimab patients successfully completed at least one 5 to 6-month interval First interval Interval at the Primary Endpointa (after 3 loading doses)b Longest interval achievedb Q8W Q8W 14% Q12W 5% Q8W 9%
Slide 10: Similar improvements in retinal thickness by Week 64 with half the doses
Tarcocimab dosed Q8W-Q24W and aflibercept dosed Q8W resulted in similar improvements in retinal thickness by Week 64, achieved with half the doses (median of 5 vs 10 doses, respectively) GLEAM: Mean Change in OCT CST Over Time 0 Aflibercept Q8W (n=230) Tarcocimab Q8W-Q24W (n=230) -50 Week 64 (SD) -1
Slide 11: Rates of common ocular adverse events were low
Rates of common ocular adverse events (≥2.0% in either study arm) were low. An imbalance in cataracts was observed Pooled GLEAM and GLIMMER Tarcocimab Aflibercept Common Ocular Adverse Events (AEs) up to Week 64 Q8W-Q24W Q8W (n=458) (n=459) Subjects with any AE in the Study Eye 220 (48.0%) 160 (34.9
Slide 12: Cataract imbalance not observed with monthly dosing in DAYLIGHT
Cataract imbalance in GLEAM and GLIMMER not observed with monthly dosing in DAYLIGHT. Mechanism underlying this observation is not yet understood & further analyses are warranted GLEAM + GLIMMER DAYLIGHT DAZZLE BEACON (DME) (wAMD) (wAMD) (RVO) Duration of Follow-Up 64 Weeks 48 Weeks 52 Weeks 24 Week
Slide 13: Rates of intraocular inflammation were low in both treatment groups
Rates of intraocular inflammation were low in both treatment groups Pooled GLEAM and GLIMMER Tarcocimab Aflibercept Intraocular Inflammation in Study Eye up to Week 64 Q8W-Q24W Q8W (n=458) (n=459) Subjects with at Least 1 Intraocular Inflammation AE* 6 (1.3%) 1 (0.2%) Tarcocimab Aflibercept Endophth
Slide 14: Why did tarcocimab not meet the primary endpoint?
Why did tarcocimab not meet the primary endpoint? 14
Slide 15: Insight #1: the matched phase was not the problem
Insight #1: the matched phase was not the problem GLEAM and GLIMMER Pooled – Mean BCVA Change Over Time -1.9 letter -4.5 letter 15 -1.8 letter difference -0.6 letter difference difference difference ETDRS Letters 10 5 Aflibercept Q8W Tarcocimab Q8W-Q24W 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60
Slide 16: Insight #2: having two fewer loading doses likely had an impact
Insight #2: having two fewer loading doses likely had an impact GLEAM and GLIMMER Pooled – Mean BCVA Change Over Time -4.5 letter 15 -1.8 letter difference -0.6 letter difference difference ETDRS Letters 10 5 Aflibercept Q8W Tarcocimab Q8W-Q24W 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Week
Slide 17: Insight #3: individualized dosing maintained initial BCVA gains
Insight #3: individualized dosing with tarcocimab maintained initial BCVA gains, with ≥50% patients consistently on 6-month dosing GLEAM and GLIMMER Pooled – Mean BCVA Change Over Time -1.9 letter -4.5 letter 15 -1.8 letter difference -0.6 letter difference difference difference ETDRS Letters 10 5 A
Slide 18: Insight #4: main difference in the maintenance phase; cataract finding main driver
Insight #4: the main difference was noted in the maintenance phase. An unexpected cataract finding was the main driver GLEAM and GLIMMER Pooled – Mean BCVA Change Over Time -1.9 letter -4.5 letter 15 -1.8 letter difference -0.6 letter difference difference difference ETDRS Letters 10 5 Aflibercept Q
Slide 19: BCVA divergence coincides with increase in cataract adverse events
The divergence of the BCVA curves between groups coincides with a relative increase in cataract adverse events in the tarcocimab group Pooled GLEAM and GLIMMER 15 Aflibercept Mean Q8W BCVA Change Tarcocimab Over Time Q8W-Q24W ETDRS Letters 10 5 Subjects with Cataract Aflibercept Q8W (n=458) Tarcocim
Slide 20: How did the pseudophakic patients do?
How did the pseudophakic patients do? 20
Slide 21: Pseudophakic patients in both groups did well and improved over time
Pseudophakic patients in both groups did well and improved over time, while receiving the same median doses as the overall groups (5 tarcocimab vs 10 aflibercept) GLEAM and GLIMMER Pooled 8080 Mean BCVA Over Time in Pseudophakic Patients ETDRS Letters 7575 7070 6565 Aflibercept Aflibercept Q8W (n=11
Slide 22: Conclusions
Conclusions GLEAM and GLIMMER did • The initial matched phase demonstrated robust efficacy not meet the primary • Individualized dosing with tarcocimab maintained initial BCVA gains, with half or more of endpoint the patients consistently on 6-month dosing Tarcocimab continues to • 1/2 of patients a
Slide 23: Thank you to all investigators, site staff and patients
Thank you to all GLEAM and GLIMMER investigators, site staff and patients Czech Republic: Axon Clinical, Oftex, Vseobecna Fakultni Nemocnice V Praze; France: Centre Paradis Monticelli, Centre Hospitalier Intercommunal de Créteil, Fondation Rothschild, CHRU Dijon Complexe Du Bocage, Hôpital de La Cro