Innovent Announces First Participant Dosed in Phase 2 Study of IBI311 (Anti-IGF-1R Monoclonal Antibody) in Patients with Thyroid Associated Ophthalmopathy

ROCKVILLE,Md.and SUZHOU,China,Feb. 15,2023 -- 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,announces that the first patient with thyroid associated ophthalmopathy (TAO) has been successfully dosed in the Phase 2 study of IBI311,a recombinant anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody.

This study (CTR20223393) is a randomized,double-blinded,placebo-controlled,phase 2 clinical study in TAO subjects. The primary objective was to evaluate the efficacy of IBI311 in improving proptosis in TAO subjects to support further clinical development of IBI311 advancing into pivotal studies.

IBI311 is an IGF-1R targeting monoclonal antibody independently developed by Innovent. 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 active TAO. Currently,no targeted drugs for TAO have been approved in China; overseas,Teprotumumab is the first and currently only IGF-1R mAb approved by the FDA for TAO.

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: " Thyroid-associated ophthalmopathy 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 TAO in China. In 2020,Teprotumumab was approved by the FDA for the treatment of TAO,providing a new option for TAO treatment,and was recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Associated Ophthalmopathy (2022),the European Group On Graves' Orbitopathy (EUGOGO) and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society. We are looking forward to IBI311,developed by a domestic biopharmaceutical company,demonstrating good efficacy and safety in the Chinese TAO population and being able to be approved and launched to market as soon as possible to relieve patients' pain."

Dr. Lei Qian,Vice President of Clinical Development of Innovent,stated: "At present,there is a great unmet medical need for TAO because of no targeted drug approved for TAO in China. IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent for the treatment of TAO and also another new molecule laid out by Innovent in the field of ophthalmology,with high druggability. Preclinical in vivo and in vitro studies have preliminarily verified that IBI311 has good safety and biological activity. The Phase 1 study in healthy volunteers also demonstrated favorable safety and tolerability of IBI311 and provide the basis for further clinical development. I believe that IBI311 will demonstrate encouraging efficacy and safety date in the current phase 2 clinical study of in TAO subjects. Innovent will cooperate with academia and promote clinical development under the leadership of Prof. Fan to bring high quality and accessible biologics to TAO patients,truly fulfilling our mission of 'To develop and commercialize high-quality biopharmaceuticals that are affordable to ordinary people ' ."

About Thyroid-associated Ophthalmopathy (TAO)

Thyroid associated ophthalmopathy (TAO) 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. TAO 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 TAO 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 TAO 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 TAO 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 TAO4.

The natural history of TAO is divided into active and inactive phases5. The most common symptoms are dry eye,ocular gritty,photophobia,lacrimation,and pressure behind the eye,while typical signs include upper eyelid retraction,eyelid edema,periorbital and conjunctival edema,and proptosis. TAO is usually mild to moderate,and about 3–5% of patients with TAO are severe,manifesting as severe pain,vision-threatening corneal ulcers,or compressive optic neuropathy6. In addition to potentially affecting vision,TAO 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 TAO 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 is recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Associated Ophthalmopathy (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 Society9as a second-line treatment option for moderately severe active TAO. There is still a large unmet clinical need in China.

About IBI311

IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent Biopharmaceuticals. 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 thyroid ophthalmopathy in Graves' disease10. 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 active thyroid ophthalmopathy and improving proptosis,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,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 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/.

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:

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:

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2. Bartley G. The epidemiological characteristics and clinical course of ophthalmologyassociated with autoimmune thyroid disease in Olmsted Country,Minnesota. Trans AmOphthalmol Soc 1994;92:477-588.

3. Edsel I. Thyroid Associated Orbitopathy. Retrieved June 7,2011,from Medscape Reference: http://emedicine.medscape.com/article/1218444-overview#a1

4. Ali F,Chorsiya A,Anjum V,Ali A. Teprotumumab (TEPEZZA): from the discovery and development of medicines to USFDA approval for active thyroid eye disease (TED) treatment. Int Ophthalmol. 2021;41(4):1549-1561.

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

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

7. 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.

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).

9. 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.

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