Abstract
Purpose :
While intravitreal anti-VEGF therapy is the standard of care treatment for retinal diseases, multiple other cytokines have been implicated in the pathophysiology of exudative retinal diseases and some, including the pro-inflammatory interleukin-6 (IL-6), have been associated with poor anti-VEGF treatment outcomes.
KSI-501 is a first-in-class bispecific trap-antibody conjugated to a phosphorylcholine biopolymer, an antibody biopolymer conjugate (ABC), that simultaneously inhibits both vascular endothelial growth factor-A (VEGF) and IL-6. The purpose of this first-in-human study is to evaluate the safety, tolerability, and bioactivity of multiple doses of KSI-501
Methods :
This is a Phase 1, open label, multi-center, first in human, multiple-ascending dose escalation study of KSI-501 in patients with diabetic macular edema (DME), with a best corrected visual acuity (BCVA) of 70 to 25 letters (20/40 to 20/320 Snellen equivalent). Four dose levels are being evaluated in escalating fashion. Each participant received a KSI-501 dose on Day 1, Week 4, and Week 8. Participants are being followed up for 24 weeks
Results :
A total of 16 patients across 6 sites in the United States have been enrolled across 4 KSI-501 dose levels. All patients have completed the multiple ascending dose phase. Mean (SD) baseline BCVA and CST were 61.7 (9.2) letters and 452.8 (113.5) microns, respectively. Results for the primary endpoint of safety and additional secondary endpoints including anatomic and visual outcomes will be presented at the meeting
Conclusions :
IL-6 is a pro-inflammatory cytokine that has been implicated in the pathophysiology of multiple exudative retinal diseases including DME and has also been implicated in other retinal diseases with an inflammatory component, such as age-related macular edema, retinal venous occlusive disease and uveitic macular edema.
KSI-501 is a novel, first-in-class biologic that inhibits both VEGF and IL-6. KSI-501 is an antibody biopolymer conjugate (ABC), designed for optimal durability in addition to its dual mechanism of action.
Results on the safety, tolerability and biological activity of KSI-501 in this first-in-human study will be presented for at the ARVO 2024 meeting.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.