Innovent Announces First Participant Dosed in Phase 1 Clinical Study of IBI333 (VEGF-A/VEGF-C Bispecific Fusion Protein) in Patients with Neovascular Age-related Macular Degeneration

ROCKVILLE,Md. and SUZHOU,China,Feb. 28,2023 --Innovent Biologics,Inc. (Innovent) (HKEX: 01801),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,today announced that the first participant with neovascular age-related macular degeneration (nAMD) has been successfully dosed in the phase 1 clinical trial of IBI333,a recombinant anti-VEGF–A and anti-VEGF-C bispecific fusion protein.

This phase 1 study（CTR20222674）aims to evaluate the safety and tolerability of intravitreal injection of IBI333 in participants with nAMD.

IBI333 is a recombinant anti-VEGF-A and anti-VEGF-C bispecific fusion protein independently developed by Innovent. It can simultaneously bind and neutralize the activities of VEGF-A and VEGF-C. Compared with anti-VEGF-A agents,IBI333 can inhibit the compensatory increased activity of VEGF-C,thus achieve a more sufficient blockage of the VEGF/VEGFR signaling,implying the potential to obtain a more desirable outcome of angiogenesis inhibition and vascular leakage reduction.

Professor Youxin Chen,Peking Union Medical College Hospital,Principal Investigator of the Study,stated: "Intravitreal injection of anti-VEGF agents has become the standard treatment for nAMD,but for refractory choroidal neovascularization (CNV),even active anti-VEGF drug intervention still cannot obtain a satisfactory therapeutic outcome. This may attribute to the involvement of other pro–angiogenic factors. Taking both VEGF-A and other proangiogenic factors inhibition into account of the design for new molecules has gradually become the trend of developing innovative therapies for nAMD treatment. We look forward to IBI333,with the design of simultaneously targeting VEGF-A and VEGF-C,can demonstrate positive safety and efficacy among nAMD patients and bring a new treatment option to patients who do not respond well or become resistant to anti-VEGF-A monotherapy,or those with specific nAMD subtypes."

Dr. Lei Qian,Vice President of Clinical Development of Innovent,stated:" IBI333 is an innovative drug independently developed by Innovent for the treatment of fundus diseases. It is an anti-VEGF–A/VEGF–C bispecific fusion protein,another dual-targeted molecule laid out by Innovent in the field of ophthalmology with global intellectual property. IBI333 has demonstrated its efficacy in inhibiting angiogenesis and vascular leakage,and has exhibited a dose-dependent efficacyin pre-clinical studies. The ongoing phase 1 study,as the first-in-human trial of IBI333,will evaluate the safety and tolerability of IBI333 in patients with nAMD and lay the foundation for future clinical development. We look forward to further in-depth collaboration with experts in clinical and academia communities to bring more encouraging innovative drugs to the clinic practice and ultimately benefit more patients and their family."

About Neovascular Age-related Macular Degeneration

Age-related macular degeneration (AMD) is a chronic progressive disease in which the focus involves the retina of the macular area,resulting in central visual impairment. nAMD is a subtype of advanced AMD characterized by the presence of choroidal neovascularization and vascular leakage,accounting for 80% to 90% of severe visual loss caused by AMD.[1]The incidence of AMD is increasing year by year in China and has now leapt to the third leading cause of blindness in China.[2]The pathological mechanism of AMD has not been fully elucidated,and it is generally recognized that angiogenesis induced by increased VEGF expression is the main cause of nAMD pathogenesis. Intravitreal injection of anti-VEGF agents is currently the standard treatment for nAMD.

About IBI333

IBI333 is a recombinant anti-VEGF-A and VEGF-C bispecific fusion protein that is independently developed by Innovent. It consists of three parts: a peptide domain derived from vascular endothelial growth factor receptor,a Fc functional region of human IgG1 and an anti-VEGF-C single-domain antibody. IBI333 can block VEGF–A–mediated signaling pathway to inhibit vascular endothelial cell proliferation,thereby inhibiting angiogenesis and reducing vascular leakage. Meanwhile,IBI333 can also reduce the epithelial cell window formation induced by VEGF-C,further reduce vascular permeability,and inhibit the binding of compensatory up-regulated VEGF-C to endogenous VEGF receptors,achieving a more comprehensive and effective blocking of intraocular VEGF signaling.

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 disease,metabolic disorder and other major diseases. On October 31,2018,Innovent was listed on the Main Board of the Stock Exchange of Hong Kong 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 36 valuable assets in the fields of cancer,metabolic disorder,autoimmune disease and other major therapeutic areas,with 8 approved products on the market. These include: TYVYT® (sintilimab injection),BYVASDA® (bevacizumab biosimilar injection),SULINNO® (adalimumab biosimilar injection),HALPRYZA® (rituximab biosimilar injection),Pemazyre® (pemigatinib oral inhibitor),olverembatinib (BCR-ABL TKI),Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review,6 assets are in Phase 3 or pivotal clinical trials,and 19 more molecules are in clinical studies.

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

For more information,please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Disclaimer:

1. This indication is still under clinical study,which hasn't been approved in China.

2. Innovent does not recommend any off-label usage.

Forward-looking statement

This news release may contain certain forward-looking statements that are,by their nature,subject to significant risks and uncertainties. The words "anticipate","believe","estimate","expect","intend" and similar expressions,as they relate to Innovent,are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs,assumptions,expectations,estimates,projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks,uncertainties and other factors,some of which are beyond the Company's control and are difficult to predict. Consequently,actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business,the Company's competitive environment and political,economic,legal and social conditions.

The Company,the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect.

References:

[1] Solomon SD,Lindsley K,Vedula SS,Krzystolik MG,Hawkins BS. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2014;8(8):CD005139. Published 2014 Aug 29. doi:10.1002/14651858.CD005139.pub3

[2] Flaxman SR,Bourne RRA,Resnikoff S,et al. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(12):e1221-e1234. doi:10.1016/S2214-109X(17)30393-5