Kodiak Sciences Inc. (Nasdaq: KOD), a precommercial retina-focused biotechnology company committed to researching, developing and commercializing transformative therapeutics, announced that the first patients have been enrolled in the global Phase 3 ALTO trial evaluating KSI-501 in patients with diabetic macular edema (DME). KSI-501 is an investigational, first-in-class bispecific therapy built on Kodiak's ABC^® Platform and designed to potently inhibit two complementary pathways implicated in retinal vascular disease: interleukin (IL)-6-mediated inflammation and vascular endothelial growth factor (VEGF)-mediated vascular permeability and neovascularization.

The ALTO trial is designed to demonstrate the superiority of bispecific (anti-VEGF, anti-IL-6) KSI-501 versus monospecific (anti-VEGF) aflibercept in patients with DME. ALTO is the second registrational Phase 3 trial of KSI-501, following the DAYBREAK study in patients with wet AMD.

ALTO explores whether dual inhibition of immune and vascular pathways can deliver deeper and more sustained disease control for patients with DME and evaluates two dosing regimens, one regimen with intensive dosing and a second regimen with individualized dosing intervals of up to every six months.

"Initiating ALTO is an important next step for KSI-501 and for our broader effort to advance multifunctional retinal medicines that address disease biology beyond VEGF alone," said Victor Perlroth, M.D., Chief Executive Officer of Kodiak. "Anti-VEGF therapies have transformed the treatment of DME, yet many patients continue to live with persistent retinal fluid, incomplete visual recovery and the burden of frequent ongoing injections. We believe that inhibiting the immune-focused IL-6 pathway alongside the vessel-focused VEGF pathway, further enhanced with the durability of our ABC Platform, may achieve deeper and more sustained control of this disease."

"It has long been believed that there is more to be gained for patients with DME by targeting mechanisms beyond VEGF, and in particular by addressing the chronic, low-grade inflammatory state that often persists in patients who have suboptimal response to anti-VEGF monotherapy," said Margaret Chang, M.D., M.S., Co-Director of Clinical Research at Retina Consultants Medical Group. "Recent results from the Phase 2 ALLUVIUM study demonstrated that IL-6 inhibition alone can lead to clinically meaningful functional and anatomic benefits in DME patients, providing evidence that the IL-6 pathway is biologically active in diabetic eye diseases and operates independently of VEGF-driven pathology. Importantly, the recent Phase 2 BARDENAS study further suggested that dual inhibition of VEGF and IL-6 may offer synergistic effects, with the potential to deliver superior vision gains and improved fluid control versus targeting either pathway alone."

"DME is a multifactorial disease in which vascular leakage, blood-retinal barrier dysfunction and immune signaling together drive retinal edema and vision loss," said J. Pablo Velazquez-Martin, M.D., Chief Medical Officer of Kodiak. "Our ALTO study is designed to rigorously evaluate whether dual inhibition of IL-6 and VEGF translates into meaningful benefit for patients, including the potential for better vision gains and greater fluid control, and through Kodiak's ABC biopolymer conjugate platform the potential for superior durability. Alongside the primary visual acuity endpoint, the study is powered for a key secondary endpoint of two-step or greater improvement on the Diabetic Retinopathy Severity Scale (DRSS), and it evaluates a regimen with dosing intervals extending to six months. Our objective is to characterize efficacy, anatomic response and durability in a single Phase 3 program."