BEDFORD, Mass. — November 24, 2025 — Leads & Copy — Ocular Therapeutix, Inc. (NASDAQ: OCUL) announced the first patient has been randomized in the HELIOS-3 Phase 3 registrational program for AXPAXLI (OTX-TKI) to treat non-proliferative diabetic retinopathy (NPDR).
The HELIOS program consists of two complementary superiority studies, HELIOS-2 and HELIOS-3, to evaluate whether early AXPAXLI treatment can meaningfully alter the course of NPDR. The studies include patients with non-center-involved diabetic macular edema (non-CI-DME) and utilize a novel ordinal ≥2-step diabetic retinopathy severity score (DRSS) primary endpoint.
According to Pravin U. Dugel, MD, Executive Chairman, President and Chief Executive Officer of Ocular Therapeutix, the HELIOS registrational program is a pivotal step toward redefining treatment for diabetic retinal disease. Dugel said that while there are more than 6 million NPDR patients in the U.S., fewer than 1% receive therapy today because of the burden of frequent injections, which AXPAXLI could alleviate with its potential for attractive durability and efficacy.
HELIOS-2 compares AXPAXLI dosed every 12 months to ranibizumab (0.3 mg), while HELIOS-3 compares 6- and 12-month dosing regimens of AXPAXLI to sham. The primary endpoint for each study is assessed at Week 52. Ocular has aligned with the FDA on the novel ordinal DRSS endpoint in its SPA agreement for HELIOS-2.
Allen Hu, MD, Principal Investigator at Cumberland Valley Retina Consultants, said the current DR treatments are burdensome and unsustainable for the working age population, unlike wet AMD, and require numerous intravitreal injections every year. This limits treatment uptake, leaving many at risk for disease progression and irreversible vision loss, Hu said. He added that AXPAXLI shows significant promise to address the unmet need for an effective treatment with durable efficacy, based on the encouraging HELIOS-1 data.
Dilsher S. Dhoot, MD, of California Retina Consultants, said the new ordinal ≥2-step DRSS endpoint Ocular has developed is an important and creative advancement for the retina field and reflects real-world treatment goals. Dhoot added that unlike binary endpoints, this ordinal measure captures changes across the full DRSS spectrum, including improvement, stability, and progression, and allows every patient to contribute to the primary analysis, enabling more efficient trials while generating clinically meaningful data.
The HELIOS-2 trial is designed as a multi-center, double-masked, randomized (1:1), parallel group superiority study to evaluate the safety and efficacy of AXPAXLI. The trial includes 432 subjects with moderately severe to severe NPDR without CI-DME randomized to receive a single dose of AXPAXLI or ranibizumab (0.3 mg) at Day 1. At Week 52, all subjects are re-dosed with their initial treatment of AXPAXLI or ranibizumab (0.3 mg) and followed for safety until the end of Year 2. Subjects are assessed monthly throughout the study, and trial subjects and designated study personnel will remain masked through the end of Year 2. The primary endpoint is the ordinal DRSS 2-step change status at Week 52 from baseline.
The HELIOS-3 trial is designed as a multi-center, double-masked, randomized (1:1:1), three-arm study to evaluate the safety and efficacy of AXPAXLI. This trial will be the second superiority study of AXPAXLI in 930 subjects with moderately severe to severe NPDR without CI-DME. Subjects in the first arm receive a single dose of AXPAXLI at Day 1 and are re-dosed at Week 24. Subjects in the second arm receive a single dose of AXPAXLI at Day 1 and sham at Week 24. Subjects in the third arm receive sham at Day 1 and at Week 24. Subjects are assessed every 12 weeks throughout the study. The primary endpoint is the ordinal DRSS 2-step change status at Week 52 from baseline.
AXPAXLI is an investigational, bioresorbable, intravitreal hydrogel incorporating axitinib, a small molecule, multi-target, tyrosine kinase inhibitor with anti-angiogenic properties, being evaluated for the treatment of wet AMD, diabetic retinopathy, and other retinal diseases.
Ocular Therapeutix, Inc. is an integrated biopharmaceutical company committed to redefining the retina experience. Ocular’s pipeline also leverages the ELUTYX technology in its commercial product DEXTENZA®, an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery in adults and pediatric patients and ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged two years or older, and in its investigational product candidate OTX-TIC, which is a travoprost intracameral hydrogel that has completed a Phase 2 clinical trial for the treatment of open-angle glaucoma or ocular hypertension.
Investor Contact:
Bill Slattery
Vice President, Investor Relations
bslattery@ocutx.com
Source: Ocular Therapeutix, Inc.
