Innovent Announces First Subject Dosed in Phase 1 Study of IBI311 (Anti-IGF-1R Monoclonal Antibody)

SAN FRANCISCO and SUZHOU,China,Aug. 18,2022 -- 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 healthy volunteer has been successfully dosed in the Phase 1 study of IBI311,a recombinant anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody.

This study (CTR20221581) is the single dose escalation Phase I study in healthy volunteers aiming to evaluate the safety and tolerability of IBI311 in healthy Chinese subjects after a single dose,thus support the clinical development of IBI311 in active thyroid associated ophthalmopathy(TAO).

IBI311 is a monoclonal antibody targeting IGF-1R developed by Innovent for the treatment of active TAO. 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,while in overseas,teprotumumab is the first and currently only IGF-1R mAb approved by the FDA for the treatment of TAO.

Professor Huifang Zhou from Department of Ophthalmology of Shanghai Ninth People's Hospital,Shanghai JiaoTong University School of Medicine,principal investigator of this study,stated: "TAO is one of the most common orbital diseases in adults and is an organ-specific autoimmune disease closely related to thyroid disease. Although not fatal,it severely affects the visual function and appearance of patients. There are currently no targeted drug approved for the treatment of TAO in China. Teprotumumab (IGF-1R antibody) was approved by the FDA in 2020,providing a new option for TAO treatment,and was recommended as second-line treatment by the European Group On Graves Orbitopathy (EUGOGO). We expect that IBI311 (IGF-1R antibody) will show good efficacy and safety in the population with TAO,so that Chinese patients can benefit from it as soon as possible. "

Dr. Lei Qian,Vice President of Clinical Development of Innovent,stated: "At present,there is a huge unmet medical need for TAO because no drug is approved for TAO in China. IBI311 is a recombinant anti-IGF-1R monoclonal antibody developed by Innovent for the treatment of TAO and is also a molecule Innovent actively advance into the clinic in the field of ophthalmology,with extremely high drug-like property. The good safety and biological activity has been preliminarily demonstrated in preclinical studies,including in vivo and vitro studies. The ongoing Phase I study,also the first-in-human trial of IBI311,will evaluate the safety and tolerability of IBI311 in Chinese healthy volunteers and provide the basis for further clinical development. We will accelerate the clinical development of IBI311 in Chinese subjects with TAO in order to obtain regulatory approval as soon as possible in China,which will not only relieve patients' pain,but also greatly reduce patients' economic burden. We will truly uphold our mission of 'To develop and commercialize high-quality biopharmaceuticals that are affordable to ordinary people.'"

About Thyroid Associated Ophthalmopathy (TAO)

TAO is an autoimmune disease involving ocular tissues and is usually associated with Graves' disease (GD). TAO occurs in approximately 25-50% of GD patients and can also be seen in other thyroid diseases,even in euthyroidism[1].

The annual incidence of TAO is estimated to be 16/100,000 in women and 2.9/100,000 in men[2]. According to disease severity,it can be divided into mild,moderate and severe TAO. Although TAO appears to affect women more often,severe cases occur more frequently in men. Patients aged 30-50 years are most commonly affected,and severe cases occur more frequently in patients over 50 years[3]. 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 TAO[4].

The natural history of TAO is divided into active and inactive phases[5]. 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 neuropathy[6]. In addition to potential effect on vision,TAO can have an extremely severe impact on the patient's appearance,social functionality and quality of life.

The European Graves Orbital Disease Study Group (EUGOGO) guidelines[7]have included the anti-IGF-1R antibody - teprotumumab as second-line therapy for moderately to severely active TAO. For active TAO in China,the currently first-line treatment is intravenous glucocorticoid,which has unsatisfactory improvement in proptosis and the risk of hormone-related systemic side effects; and second-line treatment includes other immunomodulators,which also have issues of unclear improvement of proptosis and other treatment-related risks. For inactive TAO,surgery is often used to intervene the treatment. There is a large unmet clinical need in China

About IBI311

IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent for the treatment of active TAO. 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' disease[8]. IBI311 can bind to 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,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,ophthalmology 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. 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. 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. 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.