Kodiak Sciences Inc. has reported promising new data from its Phase 1b APEX study showing that KSI-101, a novel bispecific protein, achieved clinically meaningful vision gains and rapid retinal drying in patients with macular edema secondary to inflammation (MESI). The data, presented at the Retina Society's 58th Annual Scientific Meeting in Chicago, demonstrated that over 60% of patients in the top two dose levels (5 mg and 10 mg) achieved a 3-line or more gain on the eye chart, equivalent to a 15-letter gain.
Rapid and Sustained Vision Improvements
The APEX study showed that meaningful vision gains were achieved as early as week 4, with a single dose of KSI-101 resulting in the majority of patients achieving resolution of intra-retinal and sub-retinal fluid. Over 90% of patients achieved retinal dryness by week 8, demonstrating the therapy's rapid onset of action.
Dr. Charles Wykoff, Deputy Chair of Ophthalmology at Blanton Eye Institute, who presented the data, noted that patients experienced clinically meaningful gains in best-corrected visual acuity (BCVA) and rapid retinal drying from baseline to week 12. In a separate cohort of patients with diabetic macular edema (DME), patients gained 12.0 letters and decreased 157 microns in OCT CST from baseline to week 24.
Novel Bispecific Mechanism Addresses Unmet Need
KSI-101 is a novel, potent and high strength (100 mg/mL) bispecific protein targeting interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). MESI represents a heterogenous group of serious vision-threatening retinal diseases that clinically present with macular edema and visual impairment, caused by inflammation and blood retinal barrier disruption. Currently, no good treatment options exist for patients with MESI.
Dr. Sumit Sharma, a retina and uveitis specialist at the Cleveland Clinic's Cole Eye Institute, commented on the therapy's performance: "The APEX data with KSI-101 bispecific antibody showed a drying effect that is on par with or even better than expected with the intraocular steroid implants such as Ozurdex but with none of the side effects."
Broad Activity Across MESI Spectrum
The study demonstrated that KSI-101 showed broad activity across the spectrum of MESI patients, irrespective of the location of inflammation inside the eye (anterior, intermediate, posterior or all intraocular compartments) or the specific etiology (uveitic macular edema, idiopathic macular edema, post-procedural macular edema, inflammatory choroidal neovascularization).
Dr. Victor Perlroth, Chairman and CEO of Kodiak, highlighted key differentiators of KSI-101: "its bispecific mechanism of action, as an antibody-based inhibitor of IL-6 and a trap-based inhibitor of VEGF, its rapid onset of action and powerful retinal drying effect, its favorable early safety profile allowing the selection of our two highest dose levels (5mg and 10mg) for further testing in the Phase 3 program, and its broad activity across the spectrum of MESI patients."
Phase 3 Program Actively Enrolling
Based on the APEX results, the top two dose levels tested were selected to advance into the Phase 3 program. The PEAK and PINNACLE Phase 3 studies are actively enrolling MESI subjects at the 5 mg and 10 mg dose levels versus sham treatment.
PEAK includes patients with more severe disease (moderate to severe macular edema and vision impairment) while PINNACLE includes patients with milder disease (mild macular edema and any vision impairment), as well as patients with moderate to severe macular edema with good vision. Together, the studies are designed to enroll complementary patient populations covering a wide spectrum of MESI patients.
Patients randomized to KSI-101 treatment arms will receive fixed monthly dosing for 6 doses (from Day 1 to Week 20), with subsequent individualized dosing for 6 additional visits. The primary and key secondary endpoints will be evaluated at week 24, with topline data readouts expected in 4Q 2026 or 1Q 2027.
Safety Profile and Market Potential
KSI-101 continued to be well tolerated with a favorable safety profile in both MESI and DME patients. The company believes that MESI represents a new market segment separate from the established anti-VEGF market, as there are currently no available intravitreal biologic therapies addressing the spectrum of MESI diseases.
Dr. Wykoff noted the therapy's potential broad applicability: "KSI-101 appears to be emerging as a powerful, dual-action, safe investigational therapy with potential applicability to a diverse set of pathologies that have relevance to retina specialists and uveitis specialists, many diseases of which currently have no approved treatment."
