Innovent Announces First Patient Dosed in the Phase 2 Clinical Trial of IBI302, a First-in-class Ophthalmic Anti-VEGF and Anti-Complement Bispecific Fusion Protein for Neovascular Age-Related Macular

Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, announces that the first patient has been successfully dosed in a Phase 2 clinical trial for IBI302, a first-in-class ophthalmic recombinant human anti-VEGF and anti-complement bi-specific fusion protein.

This study is a randomized, double-blind, multicenter, active-controlled Phase 2 study in subjects with active subfoveal or parafoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD). The primary objective of the study is to evaluate the efficacy and safety of IBI302 in the treatment of nAMD.

Intravitreal anti-VEGF therapy has become the standard of care for nAMD: through inhibiting VEGF, significant improvements were observed in the majority of patients' visual acuity and ophthalmologic anatomical parameters. However, many problems also come along with single anti-VEGF target drugs, such as the gradual loss of visual benefit and the appearance of retinal fibrosis or macular retinal atrophy after long-term medication. Substantial scientific studies revealed that activation of the complement pathway is not only involved in the occurrence and development of AMD, but possibly also in the pathological process of retinal atrophy and fibrosis. As the world's first bispecific fusion protein targeting VEGF and complement, IBI302 can simultaneously inhibit the proliferation of VEGF-mediated signaling pathway and reduce the inflammatory response mediated by complement activation. The results of two Phase 1 single/multiple-dose escalation studies have preliminarily shown the good safety and efficacy of IBI302 in patients with nAMD with improvement in best-corrected visual acuity, reduction in retinal thickness, and leakage and total area of neovascularization in terms of efficacy. The overall safety profile is similar to that of marketed single-target anti-VEGF drugs. Therefore, in addition to evaluating the efficacy of IBI302 in improving visual acuity and retinal thickness, the effect on macular atrophy and fibrosis will be focused in the ongoing Phase 2 study.

Professor Xiaodong Sun from General Hospital affiliated to Shanghai Jiao Tong University, the principal investigator of the study, stated "Currently, intravitreal injection of anti-VEGF drugs have become the first-line treatment for neovascular fundus diseases, but globally there's still no bispecific fusion protein in clinical studies targeting both VEGF and complement. As a global innovative drug for the treatment of ocular fundus diseases, the results of IBI302 in single-dosed and multiple-dosed studies suggest the good safety and clear efficacy in improving visual acuity and retinal thickness. The Phase 2 clinical study will explore the efficacy of this drug for macular atrophy and retinal fibrosis, which we hope could overcome the limitations of current therapies and benefit more patients."

"IBI302 is independently developed by Innovent as an first-in-class anti-VEGF and anti-complement bispecific drug that blocks VEGF while suppressing the activation of the complement system, and has been supported by the Major New Drug Project of the Ministry of Science and Technology as a Class 1 new drug. IBI302 was designed to provide more targeted treatment and interventions to the cause of nAMD by adding additional targets. We hope that we can provide physicians with a better treatment option and benefit more patients with fundus diseases and their families through the clinical development of IBI302 as an innovative target." said Dr. Lei Qian, Executive Director of Department for Medical Science and Strategies of Special Disease of Innovent.

About IBI302

IBI302 is an innovative bispecific anti-VEGF and anti-complement recombinant fully human fusion protein, which can inhibit VEGF-mediated neovascularization and complement activation pathways simultaneously. The N-terminus is a VEGF domain that can bind to the VEGF family, block VEGF-mediated signaling pathway, inhibit vascular epithelium proliferation and angiogenesis, and improve vasopermeability and reduce leakage. The C-terminus of IBI302 is the complement binding domain that can inhibit the activation of the classic pathway and alternative pathway of complement through the specific binding of C3b and C4b, and reduce the inflammatory response mediated by the complement.

The results of the Phase 1 single-dose escalation clinical trial for IBI302 were released at 2020 American Academy of Ophthalmology in November 2020. A total of 31 subjects were enrolled in the completed Phase 1 study. All subjects received a single intravitreal injection of IBI302. No serious adverse event or dose limiting toxicity was reported. The study demonstrated good safety and tolerability of IBI302. One week after administration, improved vision and reduction of retinal edema were observed. By 28 days after administration, all 31 subjects' best corrected visual acuity increased by 6 letters on average compared to baseline, the average central retinal thickness decreased by 141.2 microns compared to baseline, and the efficacy of some patients lasted until 6 weeks after administration.

About nAMD

Age-related macular degeneration (AMD) is a chronic progressive disease involving the retina in the macular area, resulting in central visual impairment. It is currently the leading cause disease of blindness in the elderly. As a main type of AMD, nAMD accounting for 15% to 20% of all AMD patients. But it is the most important cause of irreversible loss of central vision in AMD patients over 65 years of age. AMD has now leapt to the third leading cause of blindness in China with increasing incidence by years. It is generally recognized that angiogenesis induced by increased VEGF expression is the main cause of nAMD. In addition, the inflammatory response mediated by abnormal activation of complement is also considered to be an important cause of AMD, though the mechanism of action in AMD is not fully elucidated. Although anti-VEGF agents confer visual benefits and alter the course of nAMD, the current frequent mode of administration (every 4 or 8 weeks) increases the burden of medication for patients. Besides, the visual benefit of anti-VEGF drug therapy is lost by years with prolonged treatment. In about two-thirds of patients with more than 7 years of follow-up, the visual benefit conferred by anti-VEGF therapy is greatly lost. Some patients on long-term anti-VEGF therapy progress to macular atrophy or fibrosis.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 23 valuable assets in the fields of cancer, metabolic, autoimmune diseases and other major therapeutic areas, with 4 products - TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection) and HALPRYZA® (rituximab biosimilar injection) - officially approved for marketing in China, five assets in Phase 3 or pivotal clinical trials, and additional 14 molecules in clinical trials. TYVYT® was included in the National Reimbursement Drug List (NRDL) in 2019 as the historically first PD-1 inhibitor entering in NRDL and the only PD-1 included in the list in that year.

Innovent has built an international team of advanced talents in high-end biological drug development and commercialization, including many overseas experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with all relevant parties to help advance China's biopharmaceutical industry, improve drug availability to ordinary people and enhance the quality of the patients' lives.