Innovent Announces Primary Endpoint Met in the Phase 3 Clinical Trial (RESTORE-1) of IBI311 (Anti-IGF-1R Antibody) in Treating Thyroid Eye Disease and Plans to Submit NDA to the NMPA

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Innovent Biologics, Inc. achieves primary endpoint in Phase 3 study of IBI311 for Thyroid Eye Disease, showing significant efficacy and safety. Plans to submit NDA for IBI311 to NMPA. Detailed results to be shared in future conferences or journals.

ROCKVILLIE, MD. and SUZHOU, China, Feb. 19, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, today announced that the primary endpoint has been achieved in the Phase 3 registrational study (RESTORE-1) of IBI311, a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody in Chinese subjects with Thyroid Eye Disease (TED). Innovent plans to submit the new drug application (NDA) for IBI311 in the treatment of TED to the Center for Drug Evaluation (CDE) of the National Drug Administration (NMPA).

RESTORE-1 (CTR20223393) is a multicenter, randomized, double-masked, placebo-controlled Phase 2/3 clinical trial to evaluate the efficacy and safety of IBI311 in subjects with TED. The Phase 3 results of RESTORE-1 showed that the primary endpoint was successfully met: at Week 24, the proptosis responder rate in the study eye (the percentage of subjects with a reduction in proptosis of ≥2 mm from baseline in the study eye without deterioration ≥ 2 mm increase of proptosis in the fellow eye) was significantly higher in subjects treated with IBI311 than in subjects treated with placebo: 85.8% vs. 3.8%, with a difference of 81.9% (95% CI: 69.8% to 93.9%, P < 0.0001).

In addition, the key secondary endpoints of the study such as overall response rate(the percentage of subjects with a reduction in proptosis of ≥2 mm from baseline and improvement in clinical activity score ≥2 in the study eye), percentage of subjects with a clinical activity score (CAS) of 0 or 1, and mean change in proptosis from baseline in the study eye were successfully met: IBI311 significantly improved all the above parameters as compared to the placebo.

The overall safety profile of IBI311 was favorable throughout the study with no serious adverse events occurred. The efficacy and safety profiles in the Phase 3 part of the RESTORE-1 study were consistent with its Phase 2 results. Detailed results from the study will be released in medical conferences or journals in the future.

As an autoimmune disease involving ocular tissues, the annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men¹，and the estimated prevalence of clinically relevant TED ranges from 0.1% to 0.3%². At present, there is no targeted drug approved for the treatment of TED in China, while multiple clinical guidelines recommend the use of IGF-IR targeted antibody in the treatment of TED^3,4,5. Particularly, IGF-IR targeted antibody is recommended as first-line therapy for patients with clinically significant proptosis.

Professor Xianqun Fan, the leading principal investigator of the study, the Academician of the Chinese Academy of Engineering and professor of ophthalmology at the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, stated, " As an organ-specific autoimmune disease closely related to thyroid disease, TED is one of the most common orbital diseases in adults, and seriously affects the visual function and appearance of patients. At present, there is no targeted drug approved for the treatment of TED in China, and the therapeutic approaches are limited. As the principal investigator of the RESTORE-1 study, I am very pleased to see that IBI311 achieved the primary endpoint in the Phase 3 study and showed a favorable safety profile, which again demonstrates the excellent efficacy of IBI311. I look forward to sharing the detailed results of this high-quality study in the near future, and wish its successful NDA submission so as to bring benefits to Chinese TED patients as soon as possible."

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated, "There are no targeted drugs approved in the field of TED in China so far, while the treatment costs of overseas targeted drugs are beyond many patients' reach. Driven by the focus of addressing patients' unmet medical needs, we advanced the development of IBI311 rapidly. IBI311 has demonstrated significant efficacy and favorable safety in the treatment of TED in the RESTORE-1 study. We plan to submit its NDA as soon as possible, and bring high-quality, effective and safe biological drugs to Chinese patients with TED. At the same time, with the approval of SINTBILO ® (anti-PCSK9 monoclonal antibody), the NDA acceptance of Mazdutide (GLP-1R/GCGR dual agonist), and the endpoints met in phase 3 study of IBI311, Innovent is strategically establishing its innovative commercial and late-stage portfolio in the fields of cardiovascular and metabolic diseases (CVM), endocrinology and ophthalmology. We will continue to work hard to help people pursue a healthy life."

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 euthyroidism⁶.

The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men¹，and the estimated prevalence of clinically relevant TED ranges from 0.1% to 0.3%². 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 years⁷. At present, the pathogenesis of TED is not fully understood, but several studies have shown that orbital fibrous present in muscle fibers, orbital fibrous connective tissue space are key factors leading to orbital soft tissue enlargement in TED⁸.

The natural history of TED is divided into active and inactive phases⁹. 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 neuropathy¹⁰. 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, Tocilizumab and Rituximab are recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Eye Disease (2022)³, the European Group on Graves' orbitopathy (EUGOGO)⁴ and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society⁵ as the second-line treatment options for moderate to severe active TED. Teprotumumab targeting IGF-1R is recommended as first-line therapy for patients with clinically significant proptosis.

About IBI311

IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent for the treatment of TED. IGF-1R is a transmembrane tyrosine kinase receptor that plays a role in the development, metabolism, and immune regulation, and is overexpressed in OFs, B, and T cells of TED patients¹¹. 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

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable illnesses. Its pioneering therapies to treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 19 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).

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 Biologics ("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 materialize or is otherwise inaccurate.

References:

1.       Bartley G. The epidemiological characteristics and clinical course of ophthalmology associated with autoimmune thyroid disease in Olmsted Country, Minnesota. Trans Am Ophthalmol Soc 1994; 92: 477-588.                             

2.       Hiromatsu Y, Eguchi H, Tani J, Kasaoka M, Teshima Y. Graves' ophthalmopathy: epidemiology and natural history. Intern Med. 2014;53(5):353-60.

3.       Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' Orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' Orbitopathy. Eur J Endocrinol. 2021; 185 (4): G43-G67.

4.       Group of Oculoplastic and Orbital Diseases, Chinese Ophthalmology Branch, Chinese Medical Association; Group of Thyroid Diseases, Chinese Endocrinology Branch, Chinese Medical Association. Chinese Guidelines for the Diagnosis and Treatment of Thyroid Associated Ophthalmopathy (2022). Chinese Journal of Ophthalmology. 2022; 58 (9).

5.       Burch HB, et al. Management of Thyroid Eye Disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. Eur Thyroid J. 2022; 11 (6): e220189.

6.       Li Z, Cestari D M, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018; 29 (6): 528-534.

7.       Edsel I. Thyroid Associated Orbitopathy. Retrieved June 7, 2011, from Medscape Reference: http://emedicine.medscape.com/article/1218444-overview # a1http://emedicine.medscape.com/article/1218444-overview

8.       Ali F, Chorsiya A, Anjum V, Ali A. Teprotumumab (TEPEZZA): From the Discovery and Development of Medicines to USFDA Approvals for Active Thyroid Eye Disease (TED) Treatment. Int Ophthalmol. 2021; 41 (4): 1549-1561.

9.       Dolman P J. Evaluating Graves' orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012; 26 (3): 229-248.

10.   Bahn R S. Graves' ophthalmopathy. N Engl J Med. 2010; 362 (8): 726-738.

11.   Douglas RS, Naik V, Hwang CJ, et al. B cells from patients with Graves' disease erase express the IGF-1 receptor: implications for disease pathogenesis. J Immunol 2008; 181: 5768-5774.

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SOURCE Innovent Biologics

FAQ

What is the primary endpoint achieved by Innovent Biologics, Inc. in the Phase 3 study of IBI311 for Thyroid Eye Disease?

The primary endpoint achieved was a significantly higher proptosis responder rate in subjects treated with IBI311 compared to placebo, with a difference of 81.9%.

What were the key secondary endpoints met in the study for IBI311 in treating Thyroid Eye Disease?

Key secondary endpoints such as overall response rate, percentage of subjects with a clinical activity score of 0 or 1, and mean change in proptosis from baseline were successfully met by IBI311.

What is the estimated annual incidence and prevalence of Thyroid Eye Disease?

The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men, with a prevalence of clinically relevant TED ranging from 0.1% to 0.3%.

Who is the leading principal investigator of the Phase 3 study for IBI311 in Thyroid Eye Disease?

Professor Xianqun Fan is the leading principal investigator of the study, an Academician of the Chinese Academy of Engineering and professor of ophthalmology at the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.

What did Dr. Lei Qian, Vice President of Clinical Development of Innovent, mention regarding the development of IBI311 for Thyroid Eye Disease?

Dr. Lei Qian mentioned the significant efficacy and favorable safety profile of IBI311 in treating TED, emphasizing the focus on addressing patients' unmet medical needs and plans to submit NDA for IBI311.