Slide 1: Bispecific trap-antibody inhibiting IL-6 and VEGF (KSI-101): first results from Phase 1b APEX Study
Bispecific trap-antibody inhibiting interleukin-6 and vascular endothelial growth factor (KSI-101): first-time results from the Phase 1b APEX Study in patients with macular edema secondary to inflammation (MESI) Charles C. Wykoff, M.D., Ph.D. Deputy Chair of Ophthalmology, Blanton Eye Institute, Hou
Slide 2: Dysregulation of the immune system causes insults to the blood-ocular barrier
Dysregulation of the immune system causes a series of insults to the blood-ocular barrier, leading to breakdown of the barrier and release of inflammatory mediators 1 Inflammatory insults (e.g., autoimmune 2 Blood-retinal barrier breakdown allows immune cells and blood 3 IL-6 and VEGF are co-induced
Slide 3: Both IL-6 and VEGF are implicated in the pathogenesis of inflammatory macular edema
Both IL-6 and VEGF are implicated in the pathogenesis of inflammatory macular edema IL-6 VEGF • IL-6 levels are elevated in patients with ocular • Persistent inflammation triggers VEGF inflammation and further elevated in patients upregulation. VEGF levels are found to be elevated with inflammatory
Slide 4: 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 3
Slide 5: Bispecific KSI-101 restores barrier resistance greater than monotherapies
Bispecific KSI-101 restores barrier resistance from pre-existing insult greater than anti-IL-6 or anti-VEGF monotherapies alone Preclinical model of endothelial cells 150 simulating the blood-retinal barrier High barrier resistance Intact tight junctions No Exposure No Exposure VEGF + IL-6/R VEGF++K
Slide 6: What is macular edema secondary to inflammation (MESI)?
What is macular edema secondary to inflammation (MESI)? Common Common Clinical Potential common Pathophysiology Presentation therapy Inflammation VEGF IL-6 IL-6 Blood Retinal Barrier Disruption Angiogenesis Macular Edema with visual impairment KSI-101 MESI is a heterogenous group of diseases that cl
Slide 7: 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 8: 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 Enrollment patients with MESI complete Study Design: Ongoing, Open-label Phase 1b in MESI Baseline Characteristics 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 m
Slide 9: APEX KSI-101 in MESI – Meaningful vision gains achieved rapidly
APEX KSI-101 in MESI – Meaningful vision gains are rapidly achieved as early as Week 4 and ≥half of patients in the top two dose levels achieved a ≥15 letter gain Observed BCVA over time Proportion of ≥15 letter gainers 80 100 Mean Change +10.7 80 Mean ETDRS Letters 75 +12.1 Patients, % 60 +8.8 62 7
Slide 10: A single dose of KSI-101 results in the majority of patients achieving dryness
APEX KSI-101 in MESI – A single dose of KSI-101 results in the majority of patients achieving dryness. Over 90% of patients achieve dryness by Week 8 Proportion of patients Proportion of patients Observed OCT CST over timea achieving absence of IRFb achieving absence of SRFb 600 2.5 mg 5 mg 100 100
Slide 11: APEX KSI-101 in MESI – KSI-101 was well-tolerated
APEX KSI-101 in MESI – KSI-101 was 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 Tr
Slide 12: After a single dose of KSI-101, heterogenous MESI diseases show rapid responses
After a single dose of KSI-101, heterogenous MESI diseases show rapid and meaningful responses to the simultaneous IL-6 and VEGF inhibition, irrespective of the location of the inflammation or the specific macular edema diagnosis Location of inflammation Anterior Intermediate Posterior Panuveitis Da
Slide 13: APEX KSI-101 in DME – Meaningful visual and anatomical gains
APEX KSI-101 in DME – Meaningful visual and anatomical gains were achieved with KSI-101, with additional benefits with continued dosing. KSI-101 was well-tolerated Study Design: Ongoing, Open-label Mean Change in BCVA and OCT CST in DME Phase 1b in treatment-naïve DME All KSI-101 dose levels combine
Slide 14: Conclusions: KSI-101 demonstrated meaningful improvements in patients with MESI
Conclusions: KSI-101 demonstrated meaningful visual and anatomical improvements in patients with MESI in the APEX Study • MESI: group of diseases with a shared pathophysiology — inflammation & BRB disruption • Treatment with KSI-101 in MESI patients in APEX, 12-week analyses: VEGF ‒ Robust anatomic