IBI324 (OLN324, VEGF/Ang-2): A Next-Generation Ophthalmic Therapy and Its Implications for Innovent's Oncology Ambitions

Innovent Biologics' IBI324 (OLN324), a bispecific antibody targeting vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), has emerged as a promising candidate in the treatment of vision-threatening retinal diseases. As of September 2025, the drug has completed enrollment in its JADE Phase 1b trial, a U.S.-based study evaluating its potential to outperform faricimab—a current standard of care—in anatomic outcomes and treatment durability for wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) Innovent's Partner Ollin Announces Clinical Updates on IBI324 …^[1]. With topline results expected in Q1 2026, IBI324's progress underscores Innovent's strategic pivot toward next-generation ophthalmic therapies. However, investors seeking oncology breakthroughs may find themselves navigating a nuanced landscape: while IBI324 is firmly rooted in ophthalmology, Innovent's broader pipeline, including the anti-PD-1/IL-12 fusion protein IBI3026, hints at the company's ambition to redefine immuno-oncology paradigms.

Clinical Progress and Differentiation in Ophthalmology

IBI324's design leverages a dual-target mechanism to address the pathophysiology of wAMD and DME, where VEGF and Ang-2 drive vascular leakage and inflammation. According to a report by Innovent's Partner Ollin, the drug exhibits an IC50 of 0.0334 μg/mL for VEGF-A inhibition and significantly higher Ang-2 pathway activity compared to faricimab, with preclinical data showing dose-dependent efficacy in laser-induced choroidal neovascularization models IBI324/OLN324: A clinical-stage, small-format, higher-potency, high molar dose bispecific VEGF/Ang-2 inhibitor^[2]. A Phase 1 trial in DME patients demonstrated safety and efficacy, with no serious adverse events and improvements in best-corrected visual acuity and retinal thickness Innovent Presents Clinical Data of Two Ophthalmic Bispecific Antibodies IBI302 (Anti-VEGF-Anti-Complement) and IBI324 (Anti-VEGF-A/Ang-2) at AAO 2023 Annual Meeting^[3]. These results position IBI324 as a potential first-line therapy, particularly given its higher molar doses and extended durability, which could reduce the frequency of intravitreal injections—a key unmet need in retinal disease management.

The JADE trial, a randomized, multi-center study, aims to validate these advantages in a larger cohort. With over 150 patients enrolled, the trial's focus on anatomic differentiation and durability aligns with the industry's shift toward longer-acting therapies. If successful, IBI324 could challenge faricimab's market dominance, which currently holds a ~15% share in the $10 billion wAMD/DME space BioNTech to Present Clinical and Preclinical Data Across mRNA …^[4].

Clarifying Oncology Ambiguities: IBI324 vs. IBI3026

A critical nuance for investors lies in distinguishing IBI324's ophthalmic focus from Innovent's oncology pipeline. While some sources erroneously associate IBI324 with oncology, the drug's development is strictly for retinal diseases. This confusion likely stems from Innovent's parallel work on IBI3026, a first-in-class anti-PD-1/IL-12 fusion protein. Preclinical data presented at the 2025 AACR Annual Meeting revealed that IBI3026 achieved complete tumor suppression in models of melanoma, pancreatic cancer, and colorectal cancer, with a therapeutic index of 63 in cynomolgus monkeys IBI3026 / Innovent Biologics^[5]. By combining PD-1 blockade with localized IL-12 activation, IBI3026 aims to overcome resistance to existing immunotherapies—a hallmark of Innovent's oncology strategy.

This distinction is vital for assessing Innovent's long-term value. While IBI324's success in ophthalmology could generate near-term revenue, the company's oncology bets, including IBI3026, represent a high-risk, high-reward avenue. The bispecific antibody platform that underpins IBI324—characterized by small-format design and dual-target specificity—could theoretically be adapted for oncology, but no such applications are currently in development for IBI324 itself.

Strategic Implications for Innovent and Partners

Innovent's collaboration with Ollin Biosciences highlights the importance of strategic partnerships in advancing complex therapeutics like IBI324. The JADE trial's U.S. focus also signals a deliberate move into global markets, where regulatory approvals and commercialization partnerships could amplify the drug's reach. For Ollin, a biotech with limited internal R&D capabilities, IBI324 represents a potential blockbuster with minimal upfront investment, given its role as a licensing partner rather than a developer.

From an investor perspective, the key risks include the JADE trial's ability to demonstrate superior durability over faricimab and the competitive landscape in ophthalmology, where Roche's aflibercept and Genentech's bevacizumab remain entrenched. However, IBI324's differentiated mechanism and favorable safety profile in Phase 1 suggest a strong foundation for differentiation.

Redefining Oncology Paradigms: A Broader Vision

While IBI324 itself does not directly address oncology, Innovent's expertise in bispecific antibodies and its oncology pipeline, including IBI3026, position the company to contribute to the field's evolution. The success of IBI324 in ophthalmology could validate Innovent's platform, enabling cross-learning in areas such as target validation and manufacturing scalability—critical for oncology development. Furthermore, the company's participation in AACR and its focus on immune agonists like IBI3026 demonstrate a commitment to addressing tumor resistance, a persistent challenge in immuno-oncology.

Conclusion

IBI324's clinical progress in ophthalmology represents a significant milestone for Innovent, with the potential to redefine treatment standards for wAMD and DME. While the drug does not directly contribute to oncology, the company's broader pipeline and platform capabilities offer a glimpse into its long-term ambitions. For investors, the JADE trial's Q1 2026 results will be pivotal in assessing IBI324's commercial viability, while Innovent's oncology bets, particularly IBI3026, underscore the company's strategic reach beyond the eye. As the biotech landscape evolves, Innovent's ability to leverage its ophthalmic successes into oncology innovation could ultimately drive sustained value creation.