Phase 1 dose-escalation study of IBI324 - a VEGF-A/Ang-2 bispecific antibody - for the treatment of diabetic macular oedema

Sep 30, 2026

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Phase 1 multicentre, open-label dose-escalation clinical trial evaluating IBI324, a VEGF-A/angiopoietin-2 bispecific antibody, for diabetic macular oedema (DME). The study included single ascending dose (SAD) and multiple ascending dose (MAD) cohorts in 24 fovea-involving DME participants receiving intravitreal injections. Primary outcomes were dose-limiting toxicities, adverse events, and changes in vital signs and laboratory findings. No dose-limiting toxicities or treatment-related ocular serious events were reported; most TEAEs were mild to moderate. Best-corrected visual acuity improved and central subfield thickness decreased across dose groups, with sustained ‘treatment needed’-free status in MAD participants.

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Abstract

Introduction

What is already known on this topic

What this study adds

How this study might affect research, practice or policy

Original research To cite: Wang Z, Sun J, Liu K, et al. Phase 1 doseescalation study of IBI324, a VEGF-A/Ang-2 bispecific antibody, for the treatment of diabetic macular oedema. BMJ Open Ophthalmology 2026;11:e002035 . doi:10 . 1136/ bmjophth-2024-002035 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1136/bmjophth-2024-](10.1136/bmjophth-2024-)[ ](10.1136/bmjophth-2024-)[002035](002035)) . Received 1 November 2024 Accepted 12 December 2025 © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. For numbered affiliations see end of article. Correspondence to Professor Xiaodong Sun; [xdsun@sjtu.edu.cn](xdsun@sjtu.edu.cn) and Dr Xiaorong Li; [xiaorli@163.com](xiaorli@163.com) Phase 1 dose-escalation study of IBI324, a VEGF-A/Ang-2 bispecific antibody, for the treatment of diabetic macular oedema Zilin Wang,1,2,3,4 Junran Sun ,1,2,3,4 Kun Liu ,1,2,3,4 Liming Tao,5 Qinghuai Liu ,6 Miaoqin Wu,7 Shujie Lu,8 Junjie Deng,8 Li Li,8 Lei Qian,8 Xiaorong Li ,9 Xiaodong Sun 1,2,3,4 ABSTRACT Objective To evaluate the safety, tolerability and preliminary efficacy of IBI324, a vascular endothelial growth factor-A/angiopoietin-2 bispecific antibody, in participants with diabetic macular oedema (DME) . Methods and analysis This multicentre, open-label, phase 1 dose-escalation clinical trial consisted of a single ascending dose (SAD) stage and a multiple ascending dose (MAD) stage. 24 participants with fovea-involving DME were enrolled. SAD participants received a single intravitreal injection (IVT) of 0.5 mg, 2 mg or 4 mg IBI324 and were followed up until Day 42 post injection. In the MAD stage, six participants each received 3 monthly IVTs of 2 mg or 4 mg IBI324 and were followed up until determined as ‘treatment needed’ per prespecified criteria or until 24 weeks after first dose. The primary endpoints were incidence of dose-limiting toxicities (DLTs), adverse events (AEs) and changes in vital signs and laboratory test findings. Results No DLT, treatment-related AE, AE of special interest or ocular serious AE was reported. Treatmentemergent adverse events (TEAEs), all mild or moderate in severity, were observed in 4 (33 .3%) SAD participants and 11 (91 .7%) MAD participants. TEAEs of the study eye included intraocular pressure increased, conjunctival haemorrhage, allergic conjunctivitis, posterior capsularopacification and visual acuity decreased. Mean bestcorrected visual acuity increase and mean central subfield thickness decrease from baseline in the study eye were observed in all dose groups, accompanied by intraretinal fluid/subretinal fluid improvements. 16 weeks after the last dose, 7 (58.3%) MAD 2 mg and 6 (50.0%) MAD 4 mg participants remained free of ‘treatment needed’. Conclusion IBI324 was well tolerated with evidence of functional and anatomical improvement in patients with DME. Trial registration number NCT05489718 . INTRODUCTION Diabetic macular oedema (DME), characterised by retinal vascular leakage and fluid accumulation, disrupting the macular structure, is a leading cause of avoidable vision impairment and blindness worldwide.1 WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ Anti-vascular endothelial growth factor (VEGF) agents are established as first-line therapy for diabetic macular oedema (DME), although limitations such as frequent intravitreal injections and poor response to the therapy still exist. Bispecific antibodies targeting both VEGF and angiopoietin-2 (Ang-2) pathways may serve as a different treatment option for patients with DME.
WHAT THIS STUDY ADDS | | --- | | ⇒ This study assesses the safety and efficacy of IBI324, a VEGF-A/Ang-2 bispecific antibody, in patients with DME. Results showed that patients were safe and well tolerated. Best-corrected visual acuity incr

FAQs

What was the objective of the IBI324 Phase 1 dose-escalation study?

To evaluate safety, tolerability, and preliminary efficacy of IBI324 in participants with diabetic macular oedema (DME).

How was IBI324 administered in the study?

The trial used a single ascending dose (SAD) stage and a multiple ascending dose (MAD) stage, with intravitreal injections over follow-up through specified time points.

What were the main safety outcomes reported?

No dose-limiting toxicities, treatment-related adverse events, adverse events of special interest, or ocular serious adverse events were reported; most treatment-emergent adverse events were mild or moderate.

Sep 30, 2026

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