Innovent released the results of two clinical studies of IBI311 (an anti-IGF-1R monoclonal antibody) in oral presentations at the Asia-Pacific Academy of Ophthalmology Congress and International Congress of Endocrinology 2024

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Innovent Biologics, Inc. announced positive results from two clinical studies of IBI311, showing safety and efficacy in healthy subjects and patients with thyroid eye disease. The studies demonstrated that IBI311 significantly improved proptosis in patients with TED, with a favorable safety profile. The results were presented at prestigious medical congresses, highlighting the potential of IBI311 as a targeted therapy for thyroid ophthalmopathy.

ROCKVILLIE, Md. and SUZHOU, China, March 6, 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, ophthalmology and other major diseases, today announced that the results of two clinical studies of IBI311 (anti-IGF-1R monoclonal antibody),a Phase I trial in healthy subjects and a Phase II trial in patients with thyroid eye disease (TED), in the form of oral presentation at the 39^th Asia Pacific Academy of Ophthalmology (APAO) Congress and the 21^st International Congress of Endocrinology (ICE), respectively.

A Phase I Study of IBI311 (Anti-IGF-1R Monoclonal Antibody) in Chinese Healthy Volunteers
Abstract No.: 200683

The oral presentation at the 39th APAO annual meeting was based on a single dose escalation Phase 1 clinical study (NCT05480597) to evaluate the safety and tolerability of a single intravenous infusion of IBI311 in Chinese healthy volunteers. The primary endpoint of the study was safety variables, and secondary endpoints included pharmacokinetic (PK) parameters and immunogenicity results. The results showed that IBI311 was safe and well tolerated, with the most common treatment-emergent AEs being Grade 1 or 2, transient, and most resolving without treatment. All IBI311 dose groups were tested negative for anti-drug antibodies during the study. These indicated that a single intravenous administration of IBI311 at various dose levels in healthy subjects is  safe and well tolerated, and the PK profile supports dose selection for subsequent clinical development.

A Phase II Study of IBI311 for the Treatment of Thyroid Eye Disease
Abstract No.: # 792

The oral presentation at the 21^st International Congress of Endocrinology was based on a multicenter, randomized, double-masked, placebo-controlled Phase II study (NCT05795621) to evaluate the efficacy and safety of IBI311 in subjects with moderately to severely active TED. A total of 33 eligible subjects were randomized in a 2: 1 ratio to receive either IBI311 or placebo. The primary endpoint was the proptosis response rate at Week 12 of the study eye (defined as 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). After 12 weeks, all subjects received IBI311 until Week 21. The results of the study showed:

• The primary endpoint was achieved: at Week 12, the proptosis responder rate in the study eye was significantly higher in the IBI311 group than in the placebo group (59.1% vs 18.2%, OR=11. 55, P=0. 0309).
• With continued treatment and follow-up to week 24, the IBI311 treatment group achieved up to 72.7% proptosis responder rate, 3.37 mm reduction in proptosis from baseline, 88.2% diplopia responder rate (defined as diplopia improvement ≥ grade 1).
• Safety: The overall safety profile of IBI311 was favorable, with the majority of AE being mild or moderate in severity, and no treatment-emergent AE leading to drug discontinuation/interruption in the IBI311 group.

These results suggested that IBI311 significantly improves the proptosis in patients with TED in 12 weeks of treatment, and can lead to clinical benefits such as further improvement of proptosis and improvement of diplopia after continuation of treatment, with a favorable safety profile.

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 therapy approved for the treatment of thyroid ophthalmopathy in China, and the options for therapeutic interventions are limited. IBI311 is currently the most advanced candidate in the clinical development in the TED therapeutic area. As the Principal Investigator of the IBI311 series of studies, I am very pleased to see the progress of IBI311 in TED presented in an oral presentation at the ophthalmology and endocrinology Congress. This is an academic recognition of Chinese studies. I also wish that IBI311 will be approved and  available in the clinic in the near future to alleviate the disease burden of Chinese TED patients. "

Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated, "We are pleased to present the clinical development progress of IBI311 in thyroid eye disease at APAO Congress and ICE. This is another achievement of in-depth collaboration between Innovent and academia. It is  also a prestigious  recognition by the international ophthalmology and endocrinology academic community to  Innovent IBI311's progress in the treatment of thyroid eye disease. We look forward to the approval of IBI311in the near future, providing treatments to TED patients.  We will continue to make efforts to facilitate people's pursuit of a happy life and serve more patients."

About Thyroid Eye Disease (TED)

TED, the most common orbit-related disease in adults, is an autoimmune disease involving ocular tissues and 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 euthyroidism^[1].

The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men^[2]，and the estimated prevalence of clinically relevant TED ranges from 0.1% to 0.3%^[3]. According to disease severity, it can be classified 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 years^[4]. 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 TED^[5].

The natural history of TED is classified  into active and inactive phases^[6]. 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 neuropathy^[7]. In addition to potentially affecting vision, TED can have an extremely severe impact on the patient's appearance and social functioning as well as  quality of life.

Currently, the first-line treatment for moderately severe active TED is intravenous glucocorticoid therapy, which suffers from unsatisfactory improvement of proptosis and systemic side effects. The  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)^[8], the European Group on Graves' orbitopathy (EUGOGO)^[9] and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society^[10] 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 Biopharmaceuticals for the treatment of TED. IGF-1R, a transmembrane tyrosine kinase receptor that plays a role in development, metabolism, and immune regulation, is overexpressed in OFs, B, and T cells of TED patients^[11]. IBI311 can bind IGF-1R, block IGF-1R signaling pathway activation mediated by IGF-1 and other related ligands or agonistic antibodies, thus reducing the expression of downstream inflammatory factors, inhibiting the synthesis of hyaluronic acid and other glycosaminoglycan caused by OFs activation, as well as related inflammatory reactions including tissue congestion and edema. IBI311 can  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.  Li Z, Cestari D M, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018; 29 (6): 528-534.

2.  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.

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

4.  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

5.  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.

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

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

8.  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.

9.  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).

10.  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.

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 are the results of the Phase I trial of IBI311 in healthy subjects?

The results showed that IBI311 was safe and well tolerated, with no anti-drug antibodies detected in healthy volunteers, supporting its safety and tolerability.

What was the primary endpoint of the Phase I trial of IBI311?

The primary endpoint of the Phase I trial was to evaluate the safety variables, with secondary endpoints including pharmacokinetic parameters and immunogenicity results.

What was the primary endpoint of the Phase II trial of IBI311 in patients with TED?

The primary endpoint of the Phase II trial was the proptosis responder rate at Week 12, showing a significant improvement in the IBI311 group compared to the placebo group.

Who presented the results of the studies at the medical congresses?

The results of the studies were presented by Professor Xianqun Fan, the leading principal investigator, and Dr. Lei Qian, Vice President of Clinical Development of Innovent.

What did Professor Xianqun Fan state about the progress of IBI311 in TED?

Professor Xianqun Fan highlighted the importance of IBI311 as a potential targeted therapy for TED, expressing hope for its approval and availability to Chinese patients.

What did Dr. Lei Qian mention about the collaboration between Innovent and academia?

Dr. Lei Qian emphasized the achievement of in-depth collaboration between Innovent and academia in advancing the clinical development of IBI311 for thyroid eye disease.