Slide 1: KSI-101 Phase 1b APEX Study in MESI: First-Time End of Study Results
Bispecific trap-antibody inhibiting interleukin-6 and vascular endothelial growth factor (KSI-101): Phase 1b APEX Study in patients with macular edema secondary to inflammation (MESI) First-Time End of Study Results Sumit Sharma, MD Enterprise Vice Chair, Integrated Surgical Institute Medical Direct
Slide 2: KSI-101 is a first-in-class, high-strength intravitreal biologic targeting IL-6 and VEGF
KSI-101 is a first-in-class, high-strength intravitreal biologic designed to target IL-6 mediated inflammation and VEGF-mediated vascular permeability simultaneously KSI-101: high formulation strength (100 mg/mL) VEGF IL-6 IL-6 2
Slide 3: What is macular edema secondary to inflammation (MESI)?
What is macular edema secondary to inflammation (MESI)? Common Common Clinical Unifying Therapy? Pathophysiology Presentation Inflammation VEGF Macular edema with visual impairment Blood IL-6 IL-6 Retinal Barrier Disruption Angiogenesis KSI-101 MESI is a heterogenous group of diseases that clinicall
Slide 4: MESI comprises a heterogenous group of diseases with a common clinical presentation
MESI comprises a heterogenous group of diseases with a common, readily identifiable clinical presentation: macular edema with visual impairment Anterior Intermediate Posterior Panuveitis Location of Inflammation Irrespective of the anatomical location of the inflammation or the specific etiology, th
Slide 5: Phase 1b APEX study: multiple dose study of KSI-101 in patients with MESI
Phase 1b APEX study: multiple dose study of KSI-101 in patients with MESI Study Design: Ongoing, Open-label Baseline Characteristics Phase 1b in MESI Weeks 0 4 8 12 16 20 24 KSI-101 2.5 mg KSI-101 5 mg KSI-101 10 mg All KSI-101 (n=13) (n=14) (n=14) (N=41) Subjects with MESI 2.5 mg Age, years, mean (
Slide 6: Top two dose levels achieve vision gains of >10 letters by Week 4
The top two dose levels achieve meaningful vision gains of >10 letters by Week 4 and continue to improve over time, achieving a 20/25 Snellen visual acuity by Week 20 Mean Change in BCVA over time Observed BCVA over time 20 80 Mean Change Mean ETDRS Letters Mean ETDRS Letters 15 +14.4 75 +13.4 10 +1
Slide 7: More than half of patients achieved a ≥15 letter gain
More than half of patients achieved a ≥15 letter gain, with additional benefit observed in the top dose levels Proportion of ≥15 letter gainers 100 80 Patients, % 60 62 54 51 40 38 20 0 2.5 mg 5 mg 10 mg All patients (n=13) (n=13) (n=13) (n=39) Final results of the APEX study in MESI. Includes patie
Slide 8: Meaningful anatomical improvements rapidly achieved, with OCT CST <325 µm
Meaningful anatomical improvements are rapidly achieved, with OCT CST levels <325 µm observed in the top two dose levels as early as Week 1, further deepening over time Observed OCT CST over time Reading Center Data 600 2.5 mg 5 mg 10 mg 500 Mean CST (µm) 400 Mean Change 300 -116 Dryness -226 (CST 2
Slide 9: ≥90% of patients in top two dose levels achieved absence of IRF and SRF
≥90% of patients in the top two dose levels achieved absence of both intraretinal and subretinal fluid. A recurrence in IRF was observed in some patients 8 to 12 weeks after the last study treatment Proportion of patients in the 5 and 10 mg Proportion of patients in the 5 and 10 mg (pooled) dose lev
Slide 10: KSI-101 has been well-tolerated
KSI-101 has been well-tolerated KSI-101 2.5 mg KSI-101 5 mg KSI-101 10 mg All KSI-101 (n=13) (n=14) (n=14) (N=41) Summary of AEs in the Study eye, n (%) Subjects with ≥1 AEs 2 (15.4) 3 (21.4) 2 (14.3) 7 (17.1) Treatment-related AEs 1 (7.7)a 1 (7.1)b 0 2 (4.9) Serious AEs 0 0 0 0 Treatment-related se
Slide 11: Single-dose KSI-101 demonstrates rapid, meaningful responses in MESI
Single-dose KSI-101 demonstrates rapid, meaningful responses in MESI, independent of inflammation location or macular edema etiology Location of Inflammation Anterior Intermediate Posterior Panuveitis Day 1 Effect of a single Week 4 dose of KSI-101 Specific Macular Edema Etiology Juvenile Focal Chor
Slide 12: KSI-101 achieves dryness and normalizes the retinal architecture in the majority of patients
KSI-101 achieves dryness and normalizes the retinal architecture in the majority of patients KSI-101 2.5 mg Subject 1 2 3 4 5 6 7 8 9 10 11 12 13 Day 1 Week 16 Post-loading Week 24 Reactivation at W20 12 weeks since Received rescue therapy (W24 data censored) last injection KSI-101 5 mg Subject 14 1
Slide 13: Based on positive APEX data, doses advanced into Phase 3 PEAK and PINNACLE studies
Based on positive APEX data, the 5 mg and 10 mg dose levels have advanced into the Phase 3 PEAK and PINNACLE studies in MESI • KSI-101 in MESI patients in APEX showed robust anatomic and visual responses VEGF ‒ Over half of patients achieved at least a ≥15 letter gain IL-6 IL-6 ‒ >90% resolution of