Kodiak Shares KSI-101 APEX Study Results

Kodiak Sciences has announced new data from its Phase 1b APEX study evaluating KSI-101 for the treatment of macular edema secondary to inflammation (MESI). The findings were presented by Charles Wykoff, MD, PhD, Deputy Chair of Ophthalmology at the Blanton Eye Institute, during the Retina Society’s 58th Annual Scientific Meeting, held September 10–13 in Chicago.

KSI-101: A Bispecific Antibody Targeting IL-6 and VEGF

KSI-101 is an investigational, high-strength (100 mg/mL), bispecific antibody-based therapy that targets both interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). This dual mechanism is designed to address the underlying inflammation and vascular leakage in MESI.

“Although early in development, 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,” said Dr. Wykoff.

Clinical Need in MESI

Macular edema secondary to inflammation (MESI) represents a heterogeneous group of serious, vision-threatening retinal diseases. These conditions are often associated with limited treatment options, and patients typically present with macular edema and visual impairment.

APEX Study Design and Outcomes

The Phase 1b APEX study evaluated KSI-101 across two cohorts:

• Cohort 1: Patients with diabetic macular edema (DME)

• Cohort 2: Patients with macular edema secondary to inflammation (MESI)

Key Findings:

• In MESI patients, KSI-101 led to clinically meaningful gains in best-corrected visual acuity (BCVA) and rapid retinal drying from baseline to week 12.

• In the DME cohort, patients gained an average of 12.0 letters and experienced a reduction of 157 microns in OCT central subfield thickness (CST) from baseline to week 24.

• KSI-101 was well tolerated in both cohorts.

“The APEX data with KSI-101 bispecific antibody showed a drying effect that is on par with or even better than expected with intraocular steroid implants such as Ozurdex—but without the side effects,” said Sumit Sharma, MD, retina and uveitis specialist at the Cleveland Clinic’s Cole Eye Institute.

“If replicated in Phase 3 studies, KSI-101 could significantly change how we treat the many patients with macular edema secondary to inflammation.”

Advancing to Phase 3: PEAK and PINNACLE Trials

Based on the APEX findings, the 5 mg and 10 mg dose levels of KSI-101 were selected to advance into two Phase 3 studies:

• PEAK (NCT06990399)

• PINNACLE (NCT06996080)

Both trials will compare KSI-101 to sham treatment in patients with MESI. Although identical in design, they differ in patient population:

• PEAK will enroll patients with more severe disease

• PINNACLE will include patients with milder disease or moderate to severe macular edema with good vision

Together, these studies aim to evaluate KSI-101 across the full spectrum of MESI patients.

Dosing Regimen:

Patients randomized to KSI-101 will receive monthly fixed dosing for 6 injections (Day 1 to Week 20), followed by individualized dosing for an additional 6 visits from Week 24 to Week 44.

Ongoing Late-Stage Pipeline Development

Kodiak Sciences continues to expand its late-stage development portfolio, which includes GLOW2, DAYBREAK, PEAK and PINNACLE.

“As a retina community, we look forward to continuing our collaboration with Kodiak as they advance their portfolio of three late-stage medicines targeting a broad range of retinal diseases,” Dr. Wykoff added.