Exonate first-in-class eye drop phase 1b/2a trial data demonstrate safety and biological activity in treatment of diabetic retinopathy and diabetic macular oedema

March 5, 2024 – Clinical Trials – Exonate, clinical trials, diabetic macular oedema, diabetic retinopathy

• EXN407 is the first topical SRPK1 inhibitor to demonstrate both safety and signals of biological response as monotherapy for these indications
• Data generated fully supports continued clinical development of EXN407 into the CLEAR-DM Phase 2b study
• Full phase 1b/2a data selected for presentation at ARVO 2024.

5 March 2024 — Cambridge, UK and Nottingham, UK — Exonate, a biotechnology company developing novel, non-invasive, small-molecule therapeutics for patients with retinal vascular diseases, today announced the data from a successful phase 1b/2a trial for lead candidate EXN407. This data demonstrates the safety and tolerability of EXN407, as well as clear indications of biological activity, positioning it well for further development as the first topical treatment for retinal vascular diseases such as diabetic retinopathy and diabetic macular oedema. 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 non-proliferative diabetic retinopathy (NPDR) and mild diabetic macular oedema. 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.

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 non-invasive treatment for these devastating, sight-threatening conditions, and the favourable 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 IIb 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.

About Exonate

Exonate is a biotechnology company developing novel, non-invasive, small-molecule therapeutics for patients with retinal vascular diseases which may lead to vision loss. The company’s pipeline is built around inhibition of pro-angiogenic VEGF by influencing splice patterns, for the treatment of conditions that have the formation of new blood vessels as a significant contributor, such as wet Age-Related Macular Degeneration (wet AMD) and Diabetic Macular Oedema (DME). Developed to penetrate to the back of the eye, reach the retina and prevent growth of blood vessels, Exonate’s treatments for retinal diseases are being developed as eye drops, eliminating the need for monthly injections into the eye, laser surgery or use of steroids, without sacrificing potency or permeability. There is a large unmet market opportunity for a topical therapy for diabetic retinopathy and diabetic macular oedema that can treat the conditions earlier in the disease process. Exonate’s lead asset, EXN407, has the potential to be the first topical treatment for retinal vascular diseases, including diabetic retinopathy and diabetic macular oedema. EXN407 has shown encouraging signs of efficacy, alongside meeting all endpoints, in a phase 1b/2a trial in diabetic patients with retinal eye disease (diabetic macular oedema). The company is led by a highly experienced management team, and has a strong foundation of scientific expertise, with cross-disciplinary experience in medicine and drug development. To find out more information about Exonate’s therapeutic pipeline for diabetic complications and other indications, as well as our clinical programmes, please visit: www.exonate.com/