Exonate to Launch Phase 2b CLEAR-DE Trial for EXN407 Eye Drop in NPDR and DME

Biotechnology company Exonate has announced its plans to initiate a Phase 2b clinical trial for its investigational therapy EXN407, a first-in-class topical SRPK1 inhibitor designed for the treatment of non-proliferative diabetic retinopathy (NPDR) and diabetic macular edema (DME). The trial, named CLEAR-DE (Clinical Evaluation of a New Drop for Alleviating Retinopathy in Diabetic Eye Disease), aims to evaluate the efficacy, optimal dosing, and safety profile of this twice-daily eye drop formulation in patients with early-stage diabetic eye disease.

Exploring a Non-Invasive Approach to Diabetic Eye Disease

EXN407 represents a novel, non-invasive approach to treating NPDR and DME, conditions typically managed with intravitreal injections.

“The phase 1b/2a data demonstrated the clear potential of EXN407 as a non-invasive treatment for diabetic eye disease,” said Catherine Beech, MB, ChB, OBE, CEO of Exonate. “This therapy could transform the treatment landscape for early-stage disease by providing clinical benefit while avoiding the burden of injections, representing a significant advancement for patients and physicians alike.”

The company is actively seeking strategic partners to support the execution of the upcoming Phase 2b program.

Phase 1b/2a Results Support Advancement

The decision to advance to the Phase 2b trial is supported by positive findings from Exonate’s Phase 1b/2a study completed in March 2024. The earlier trial met all primary safety and tolerability endpoints, with no drug-related serious adverse events reported. Patient compliance was high throughout the study, and exploratory efficacy data showed a reduction in vascular leakage, which is considered a key pathological driver in diabetic retinopathy.

Details of the Upcoming CLEAR-DE Phase 2b Trial

The Phase 2b CLEAR-DE trial is scheduled to begin in early 2026 and will enroll 140 patients across multiple international sites, including Australia, China, and countries in the Middle East. The goal is to build upon prior safety data and gather critical insight into dose optimization and therapeutic potential of EXN407 in real-world clinical settings.

Mechanism of Action: Targeting SRPK1

EXN407 is the first known topical formulation of a selective serine-arginine protein kinase 1 (SRPK1) inhibitor. Its mechanism of action involves the selective inhibition of pro-angiogenic VEGF isoforms, which are responsible for the formation of abnormal, leaky blood vessels in the retina. Additionally, EXN407 modulates VEGF expression through alternative mRNA splicing, offering a targeted approach to addressing key pathways involved in disease progression.