At the virtual Angiogenesis, Exudation and Degeneration 2026 symposium held on February 7th 2026, Carl Regillo presented clinical data from the phase 1b trial for danegaptide, looking at 24 patients with non-proliferative diabetic retinopathy (NPDR) with associated macular edema.
Danegaptide is the first oral drug designed by Breye Therapeutics – a clinical development stage, ophthalmology-focused biotech company – specifically for diabetic retinopathy (DR), and the phase 1b trial was conducted across 11 clinical sites in the US, Germany, and the UK, to assess the tolerability, safety, pharmacokinetics (PK), and early signs of biological activity in the drug.
We spoke with Regillo about danegaptide, and what these initial study findings reveal about Breye Therapeutics’ lead oral asset.
Can you explain a little about danegaptide and its mode of action?
Orally administered danegaptide reaches the capillaries from the luminal side and has two complementary mechanisms of action:
A) It stabilizes Cx43 based gap-junctions between endothelial cells and between endothelial cells and pericytes. This leads to a strengthening of the inner blood-retinal barrier composed of gap-junctions, tight junctions, and adhesion junctions.
B) Danegaptide partly protects from VEGF-induced down-regulation of TNFSF15 (which acts as a natural brake on the VEGFR2 receptor) thereby working as a functional antagonist to VEGF.
The combined effects of A and B lead to reduced vascular leakage and protection from further capillary breakdown.
What unmet clinical diabetic retinopathy need initially motivated this study into danegaptide?
Today, we can treat the most advanced 10-15% of patients with DR with office-based injected therapies. Specifically, patients who progress to proliferative disease (PDR) or macular edema to a point where vision is compromised are offered intravitreal (IVT) anti-VEGF injections.
While we know that patients with non-proliferative diabetic retinopathy (NPDR) without DME are responsive to existing anti-VEGF therapies to reduce the risk of vision-threatening complications, the repeated needle injections are not acceptable at this earlier stage of disease. Orally administered danegaptide has the potential to treat both eyes and at earlier stages of disease to halt the core pathologies of vascular leakage and capillary breakdown.
What were the main clinical findings of your study?
The main objectives of the trial were to show safety, tolerability, and PK measures in the targeted therapeutic range. These objectives were all met with good results. Additionally, the study explored early signs of biological activity, and we were encouraged to see more than half of the study eyes showed retinal imaging data associated with reductions in vascular leakage, a good handful of participants with noteworthy responses, and a statistically significant reduction in edema scores by the end of the study.
If your findings are confirmed in phase 2, how do you think an oral therapy might change the way ophthalmologists approach treating NPDR?
There is a large and growing unmet medical need to treat patients with NPDR, but the existing injection-based therapies are too burdensome for these earlier stages of the disease. Having access to an oral therapy would enable earlier intervention to reduce the risk of progression to more advanced forms of DR and associated vision-threatening problems like DME and neovascularization. Orally administered danegaptide could potentially also be used as an adjunct to existing IVT therapies to help reduce office visit and injection treatment burden for both patients and providers.
Do you think this sort of oral therapy could improve patient adherence and long-term outcomes?
Most type 2 diabetic patients receive orally administered anti-diabetic medications, and danegaptide could be added with limited additional burden for patients in daily routines. The aim would be to halt progression and even improve the degree or severity of retinopathy and, thereby, lower the risk for vision-threatening complications. For patients with advanced disease, we know that about half of the patients become non-compliant after a year of repeated IVT injections and, in these patients, switching to an oral therapy for maintenance and durability of response could help improve adherence and outcomes.
Are there particular patient populations you envisage benefiting most from an early oral intervention?
Patients with earlier stages of NPDR, for whom there are no good treatment options today.
From a retina specialist’s perspective, what would success look like for danegaptide in phase 2?
If we achieve anything close to the 60% response rates (³2-step reduction in DRSS scores) observed for the IVT-based therapies in patients with moderately severe or severe NPDR, this would clearly constitute great success. If patient responses could also be maintained after an induction regimen of IVT-based therapies, this would be an added benefit.
