Innovent Announces First Patient Dosed in Phase 1 Study of IBI324 (VEGF-A/Ang-2 Bispecific Antibody) in Patients with Diabetic Macular Edema

SAN FRANCISCO and SUZHOU, China, Aug. 7, 2022 /PRNewswire/ -- 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, announces that the first patient with diabetic macular edema (DME) has been successfully dosed in the Phase 1 study of IBI324, a potential first-in-class ophthalmic recombinant human anti-VEGF-A and anti-Ang-2 bispecific antibody.

This Phase 1 dose escalations study (CTR20221524) aims to evaluate the safety and tolerability of intravitreal injection of IBI324 in subjects with diabetic macular edema (DME).

IBI324 is a dual-target specific recombinant fully humanized anti-VEGF-A and anti-Ang-2 bispecific antibody developed by Innovent, which can achieve anti-angiogenesis, vascular stabilization and inflammation inhibition by blocking both VEGF-A and Ang-2, aiming to bring more potential clinical benefits to DME patients, such as prolonging the dosing interval and improving treatment compliance.

Professor Xiaodong Sun, Vice President and Director of the Eye Center of the First People's Hospital of Shanghai Jiao Tong University, principal investigator of this study, stated: "Anti-VEGF ophthalmic agents are now the standard of care for many neovascular fundus diseases. However, existing anti-VEGF drugs require repeated intravitreal injections every 4 to 12 weeks.  Frequent injections and follow-up reduce patient compliance with treatment, resulting in poor long-term treatment efficacy in many patients. For example, persistent macular edema remains in approximately 40% of patients with DME under standard treatment. The multi-targeted agents based on anti-VEGF has become the current trend in drug development for fundus diseases. We expect IBI324 to demonstrate positive safety and bioactivity results in the DME population by blocking both VEGF-A and Ang-2 targets and lengthen the dosing interval, leading to more options for clinical treatment."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: "IBI324 is an innovative molecule independently developed by Innovent for the treatment of fundus diseases. It is an anti-VEGF/ anti-Ang-2 bispecific antibody and another innovative dual-target molecule Innovent advances to clinic in the field of ophthalmology. It deploys the global pioneering antibody design in the form of scFv (single-chain Fv) + VHH (single-domain antibody) and owns global intellectual property rights. The results of preclinical studies showed the effect of IBI324 in inhibiting angiogenesis and reducing vascular leakage, indicating a potential advantage of a longer dosing interval compared with the competitors. The first-in-human Phase 1 study will evaluate the safety and tolerability of IBI324 in the patients with DME and provide solid ground for further clinical development. We look forward to further in-depth collaboration with experts in clinical and academia community to bring more potential innovative drugs to the clinic and ultimately benefit more patients and families."

About Diabetic Macular Edema (DME)

Diabetic retinopathy is a complication of diabetes, caused by high blood sugar levels damaging the retinal microvascular, DME is a chronic progressive disease that causes impaired vision or even blindness due to swelling of the central part of the retina. The incidence of diabetic retinopathy has gradually increased, and it is also one of the main causes of blindness in working-age adults and the elderly¹, which seriously affects the quality of life of diabetic patients, and places a heavy financial burden on society². Hyperglycemia and associated metabolic pathways, oxidative stress as well as inflammation in diabetes are thought to be closely related to the pathogenesis of diabetic retinopathy and DME, which can lead to neurodegeneration, early microvascular damage, and damage to the neurovascular unit³. In this state, VEGF expression is upregulated, leading to neovascularization, disruption of vascular endothelial cell integrity, and vascular leakage caused by damage to the blood-retinal barrier; Ang-2, by binding Tie2 receptor on vascular endothelium, can disrupt the stability of the endothelial cell layer and cause leakage⁴, which acting in combination with VEGF leads to the development of DME.

About IBI324

IBI324 is a bispecific anti-VEGF and anti-Ang-2 recombinant fully humanized antibody independently developed by Innovent Biologics. The N-terminus can block VEGF-A-mediated signaling pathway and inhibit the growth and proliferation of vascular endothelial cells, thereby inhibiting angiogenesis, reducing vascular permeability and vascular leakage; the C-terminus of IBI324 is an Ang-2 binding domain independently screened by Innovent that can specific inhibit the binding of Ang-2 to Tie-2 receptor, and therefore improve the sensitivity to other inflammatory factors, further stabilize blood vessels and inhibit vascular leakage. IBI324 can inhibit neovascularization and stabilize blood vessels and inhibit inflammation that mediated by VEGF-A and Ang-2, which may bring more clinical benefits to patients with DME.

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, ophthalmology 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 34 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 7 products approved for marketing in China – TYVYT^® (sintilimab injection), BYVASDA^® (bevacizumab biosimilar injection), SULINNO^® (adalimumab biosimilar injection), HALPRYZA^® (rituximab biosimilar injection) , Pemazyre^® (pemigatinib oral inhibitor), NAILIKE(olverembatinib) and Cyramza^® (ramucirumab), 3 asset under NMPA NDA review, 4 assets in Phase 3 or pivotal clinical trials, and an additional 20 molecules 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/.

Note:

TYVYT^® (sintilimab injection) is not an approved product in the United States.

BYVASDA^® (bevacizumab biosimilar injection), SULINNO^®, and HALPRYZA^® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT^® (sintilimab injection, Innovent)

BYVASDA^® (bevacizumab biosimilar injection, Innovent)

HALPRYZA^® (rituximab biosimilar injection, Innovent)

SULINNO^® (adalimumab biosimilar injection, Innovent)

Pemazyre^® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre^® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

CYRAMZA^® (ramucirumab, Eli Lilly). Cyramza^® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

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 Statements

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 Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. Innovent 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 Innovent 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 Innovent'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, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent 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.

Reference:

1. Wong TY, Cheung CMG, Larsen M, Sharma S, Simó R. Diabetic retinopathy. Nat Rev Dis Primer. 2016;2:16012.
2. Chinese Diabetes Society Retinopathy Group, Chin J Diabetes Mellitus, 2018,10(4): 241-247.
3. Kusuhara S, Fukushima Y, Ogura S, Inoue N, Uemura A. Pathophysiology of Diabetic Retinopathy: The Old and the New. Diabetes Metab J. 2018;42(5):364-376.
4. Maisonpierre PC, Suri C, Jones PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277(5322):55-60.

SOURCE Innovent Biologics