Innovent Announces First Participant Dosed in Phase 3 Study (RESTORE) of IBI311 (Anti-IGF-1R Monoclonal Antibody) in Patients with Thyroid Eye Disease

ROCKVILLE, MD. and SUZHOU, China, May 7, 2023 /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 Thyroid Eye Disease (TED) has been successfully dosed in the Phase 3 study (RESTORE) of IBI311, a recombinant anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody.

The RESTORE study (CTR20223393) is a randomized, double-blinded, placebo-controlled, phase 3 clinical study evaluating the efficacy of IBI311 in improving proptosis in TED subjects to support the potential new drug application of IBI311. The primary endpoint is the difference in the improvement in proptosis degree responder rate of the study eye in the treatment group compared with the placebo group at week 24.

IBI311 is an IGF-1R targeting monoclonal antibody independently developed by Innovent for the treatment of TED. Currently no biological agent for TED has been approved in China. By blocking the binding of IGF-1 and IGF-2 to IGF-1R, IBI311 inhibits IGF-1R signaling pathway activation and reduces the expression of downstream inflammatory factors, thereby inhibiting the adipocytosis of orbital fibroblasts (OFs) and the synthesis of hyaluronic acid and other glycosaminoglycans due to the activation of OFs, as well as the inflammatory response, thus reduces disease activity and improve proptosis, diplopia, ocular congestion and edema in patients with TED.

The principal investigator, Professor Fan Xianqun from Ophthalmology Department of the Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, an academician from the Chinese Academy of Engineering, stated: " TED is one of the most common orbital diseases in adults and is an organ-specific autoimmune disease closely related to thyroid disease, which can severely affect the visual function and appearance of patients. There are currently no targeted drugs approved for TED in China. Significant efficacy signals have been observed in IBI311 phase 2 clinical study, including the regression of exophthalmos and the improvement of the Clinical Activity Score (CAS), and a good safety profile was also demonstrated. We are confident that IBI311, developed by a domestic biopharmaceutical company, will demonstrate good efficacy and safety in the Chinese TED patients and be able to be launched to market as soon as possible to address patients' urgent needs."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: "At present, there is a great unmet medical need for TED because of no targeted drug approved for TED in China. IBI311 is an ophthalmic drug candidate developed by Innovent for the treatment of TED with high druggability, and will potentially add synergic value to our product portfolio in endocrinology and metabolism field. Preclinical in vivo and in vitro studies, the Phase 1 study in healthy volunteers as well as the Phase 2 study in TED subjects demonstrated that IBI311 has favorable safety and tolerability characteristics, and significant efficacy signals were also observed, which has laid a good foundation for the development of Phase 3 RESTORE study. Innovent will continue cooperating with academia and advance clinical development under the leadership of Prof. Fan, and plans to submit the NDA after the Phase 3 study completion to bring high quality and accessible biologics to Chinese TED patients."

About Thyroid Eye Disease (TED)

TED is an autoimmune disease involving ocular tissues and is usually associated with Graves' disease (GD) and is the most common orbit-related disease in adults. TED occurs in approximately 25 to 50% of GD patients and can also be seen in other thyroid diseases, even in euthyroidism¹.

The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men². According to disease severity, it can be divided into mild, moderate and severe. Although TED appears to affect women more often, severe cases occur more frequently in men. Patients aged 30 to 50 years are most commonly affected, and severe cases occur more frequently in patients over 50 years³. At present, the pathogenesis of TED is not fully understood, but several studies have shown that OFs present in muscle fibers, orbital fibrous connective tissue space are key factors leading to orbital soft tissue enlargement in TED⁴.

The natural history of TED is divided into active and inactive phases⁵. The most common symptoms are dry eye, ocular gritty, photophobia, lacrimation, diplopia, and pressure behind the eye, while typical signs include upper eyelid retraction, eyelid edema, periorbital and conjunctival edema, and proptosis. TED is usually mild to moderate, and about 3–5% of patients with TED are severe, manifesting as severe pain, vision-threatening corneal ulcers, or compressive optic neuropathy⁶. In addition to potentially affecting vision, TED can have an extremely severe impact on the patient's appearance and social functioning and quality of life.

Currently, the first-line treatment option for moderately severe active TED is intravenous glucocorticoid therapy, which suffers from unsatisfactory improvement of proptosis and systemic side effects, and second-line treatment includes other immunomodulators, which also have risks related to unclear improvement of proptosis and treatment.

Teprotumumab, TociIizumab and Rituximab are recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Eye Disease (2022)⁷, the European Group On Graves' Orbitopathy (EUGOGO)⁸ and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society⁹ as the second-line treatment options for moderate to severe active TED. Teprotumumab is recommended as first-line therapy for patients with clinically significant ophthalmopathy.

About IBI311

IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent Biopharmaceuticals for the treatment of TED. IGF-1R is a transmembrane tyrosine kinase receptor that plays a role in development, metabolism, and immune regulation, and is overexpressed in OFs, B, and T cells of TED patients¹⁰. IBI311 can bind IGF-1R, block IGF-1R signaling pathway activation mediated by IGF-1 and other related ligands or agonistic antibodies, reduce the expression of downstream inflammatory factors, thereby inhibiting the synthesis of hyaluronic acid and other glycosaminoglycan caused by OFs activation, as well as related inflammatory reactions including tissue congestion and edema; inhibit adipocyte cellularization of OFs, thereby reducing the disease activity of patients with TED and improving proptosis, diplopia, ocular congestion and edema and other symptoms and signs.

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 in the fields of oncology, metabolism, autoimmunity,, 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 35 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, 5 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/.

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.

Retsevmo® (selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Disclaimer: 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:

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3.	Edsel I. Thyroid Associated Orbitopathy. Retrieved June 7, 2011, from Medscape Reference: http://emedicine.medscape.com/article/1218444-overview#a1
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8.	中华医学会眼科学分会眼整形眼眶病学组, 中华医学会内分泌学分会甲状腺学组. 中国甲状腺相关眼病诊断和治疗指南 （2022年）.中华眼科杂志. 2022;58(9).
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