THN391 enters phase 1b trial for diabetic macular edema

Therini Bio has dosed the first patients in a phase 1b multiple ascending dose trial evaluating THN391, an investigational intravitreal anti-inflammatory monoclonal antibody, for diabetic macular edema (DME).¹ The early-stage study is intended to assess the safety and preliminary biological activity of a fibrin-targeting approach in a disease currently treated primarily with anti–vascular endothelial growth factor (VEGF) agents.

“The dosing of the first cohort of patients in our THN391 trial represents a significant milestone for Therini Bio,” Joel Naor, MD, chief medical officer of ophthalmology at Therini Bio, said in the announcement. “By targeting fibrin-driven inflammation, THN391 has the potential to enhance retinal health, improve treatment outcomes, and preserve vision in patients with DME.”¹

The ongoing phase 1b trial will include 3 dose cohorts, with each patient receiving 3 monthly intravitreal injections of THN391. Safety is the primary focus at this stage, with preliminary efficacy and biological activity assessed through central subfield thickness, visual acuity, and exploratory biomarkers. The company said initial data are expected in the fourth quarter of 2026.¹

THN391 is described by Therini as a high-affinity, humanized monoclonal antibody designed to selectively block an inflammatory epitope of fibrin without disrupting coagulation. The proposed rationale is that loss of vascular integrity in DME permits fibrin deposition, contributing to chronic neuroinflammation and neuroretinal degeneration.

DME remains a major cause of vision loss in patients with diabetic retinopathy. Intravitreal anti-VEGF therapy has reshaped treatment over the past decade, with ranibizumab, aflibercept, bevacizumab, and more recently faricimab supported by randomized trial data showing improvements in visual acuity and retinal thickness in appropriately selected patients.^2-4 In RISE and RIDE, monthly ranibizumab improved visual outcomes compared with sham injections in patients with DME.² In the DRCR Retina Network Protocol T trial, aflibercept, bevacizumab, and ranibizumab all improved vision, with aflibercept showing greater benefit at 1 year among patients with worse baseline visual acuity.³ Faricimab, which inhibits both angiopoietin-2 and VEGF-A, demonstrated noninferior visual acuity gains vs aflibercept in the YOSEMITE and RHINE trials, with some patients maintained on extended dosing intervals.⁴

Against that background, THN391 represents a different therapeutic concept: targeting inflammatory consequences of vascular dysfunction rather than VEGF-mediated permeability alone. Whether fibrin blockade adds clinically meaningful benefit beyond currently available anti-VEGF or bispecific anti-VEGF/Ang-2 therapy remains unknown. The present trial is not designed to establish comparative efficacy and is expected to provide early safety, dosing, and biomarker signals rather than definitive visual outcome data.

Therini also reported selection of THN622 as its ophthalmology lead candidate. THN622 is a bispecific antibody designed to block both the fibrin inflammatory epitope and VEGF. The company stated that the dual approach is intended to address VEGF-mediated leakage and fibrin-associated inflammation in retinal diseases characterized by vascular dysfunction, including DME.¹

References

1. Therini Bio doses first patients in phase 1b trial of novel anti-inflammatory therapy, THN391, for diabetic macular edema. GlobeNewswire. May 27, 2026. Accessed May 28, 2026. https://www.globenewswire.com/news-release/2026/05/27/3302124/0/en/therini-bio-doses-first-patients-in-phase-1b-trial-of-novel-anti-inflammatory-therapy-thn391-for-diabetic-macular-edema.html

2. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801. doi:10.1016/j.ophtha.2011.12.039

3. Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193-1203. doi:10.1056/NEJMoa1414264

4. Wykoff CC, Abreu F, Adamis AP, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE). Lancet. 2022;399(10326):741-755. doi:10.1016/S0140-6736(22)00018-6