Phase 1b/2a Trial of Exonate's Eye Drop Demonstrates Safety and Biological Activity in Treatment of DR and DME
UK-based Exonate announced data from a phase 1b/2a trial for lead candidate EXN407 demonstrating safety and tolerability of the drug candidate, as well as clear indications of biological activity, according to a company news release. The data position the company for further development as the first potential topical treatment for retinal vascular diseases such as diabetic retinopathy (DR) and diabetic macular edema (DME). Exonate is now planning to progress EXN407 to the CLEAR-DM (Clinical Evaluation of a New Eyedrop for Alleviating Retinopathy in Diabetic Macular Oedema) phase 2b clinical trial.
EXN407 is a twice-daily formulation, comprised of a small molecule SRPK1 inhibitor. The eye drop formula exploits SRPK1 involvement in the alternative splicing of vascular endothelial growth factor (VEGF), a protein heavily involved in the regulation of blood vessel growth. Through inhibition of SRPK1, EXN407 can selectively target pro-angiogenic isoforms of VEGF that lead to vascular retinal disease progression via aberrant growth of leaky blood vessels within the eye.
The mild NPDR/DME (NCT04565756) clinical study assessed the safety, tolerability and signals of biological response to EXN407 monotherapy in a double-masked, placebo-controlled phase 1b/2a dose-ranging clinical trial in treatment-naïve patients with mild/moderate nonproliferative diabetic retinopathy (NPDR) and mild DME. The independent Dose Escalation Committee characterised EXN407 as safe and well-tolerated, with 100% of patients completing the study without requiring anti-VEGF rescue, and no major or serious adverse events reported relating to EXN407. Moreover, EXN407 exhibited high levels of tolerability, with drop comfort scores similar to placebo and artificial tears, according to Exonate.
In addition to the primary safety and tolerability endpoints, the study concluded that there were promising signals of biological response from EXN407, demonstrating sustained decreases in macular thickness, relative to the placebo group and comparable to previously reported anti-VEGF injections. The trial further noted that EXN407 treatment led to a significant decrease in vascular leakage (60% of EXN407-treated patients relative to 20% placebo) and that EXN407 inhibited further increases to vascular leakage (10% of EXN407-treated patients relative to 50% placebo).
“The phase 1b/2a data demonstrate the clear potential of EXN407 as a noninvasive treatment for these devastating, sight-threatening conditions, and the favorable safety profile and biological activity of EXN407 support its continued clinical development in retinal vascular diseases,” said Catherine Beech, chief executive officer of Exonate. “The results suggest that topical ocular EXN407 may provide clinical benefit and substantially reduce the injection burden for patients with diabetic eye disease. We look forward to engaging with strategic partners to support the CLEAR-DM phase 2b trial, which has been designed to fully demonstrate the clinical benefits of EXN407 in NPDR/DME.”
Full results of the phase 1b/2a will be presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in May 2024: https://www.arvo.org/annual-meeting/.