Innovent Announces Results of Phase 3 Clinical Study of Tafolecimab（IBI306）in Chinese Patients with Hypercholesterolemia were Published in JACC:Asia

ROCKVILLE, U.S. and SUZHOU, China, Jul 17, 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 results of phase 3 clinical trial (Study code: CREDIT-4) of recombinant fully-human anti-PCSK9 monoclonal antibody (Tafolecimab injection, R&D code: IBI306) in Chinese patients with hypercholesterolemia were published as a research article in JACC:Asia, and the journal also published a comment by Professor Jianjun Li on tafoleicmab named “Tafolecimab, a Novel Member of PCSK9 Monoclonal Antibodies, Is Worth Expecting in a Chinese Population”. PCSK9 inhibitors, which can potently reduce LDL-C levels with a good safety profile, have been gradually recognized by clinicians as novel therapies in recent years. Although there are various imported PCSK9 inhibitors marketed in China, there are some limitations in terms of economy and convenience. Tafoleicmab is an innovative drug independently developed by Innovent. It is the first PCSK9 inhibitor that take the lead in carrying out long-term, large-scale, randomized and double-blind phase III clinical studies in China（CREDIT-1，CREDIT-2 and CREDIT-4）, and exploring optimized treatment regimen with long-interval dosing. The new drug application (NDA) of tafoleicmab is currently under review by the NMPA of China, and tafoleicmab will potentially be the first approved domestic PCSK9 inhibitor in Chinese market. The results published in JACC:Asia are based on CREDIT-4, a randomized, double-blind, placebo-controlled phase 3 clinical study (ClinicalTrials.gov NCT04709536) to assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. Patients diagnosed with heterozygous familial hypercholesterolemia (HeFH) or at high or very-high cardiovascular risk with non-familial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L, were randomized 2:1 to receive tafolecimab or placebo 450 mg every 4 weeks (Q4W) in the 12-week double-blind treatment period. After the 12-week double-blind treatment period, patients in placebo group crossed over to receive tafolecimab 450 mg Q4W for 12 weeks.The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. The results showed that tafolecimab treatment can significantly reduce the LDL-C level. The least squares mean percent change in LDL-C level from baseline to week 12 was –68.9% in the tafolecimab group and –5.8% in the placebo group (difference: –63.0%; [95%CI: –66.5%, –59.6%]; P <0.0001). More patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L, and LDL-C <1.4 mmol/L at week 12 than placebo group (all P <0.0001). Furthermore, tafolecimab treatment also resulted in a significant decrease in lipoprotein(a) levels. The least squares mean percent change from baseline to week 12 in lipoprotein(a) levels was −45.4% in the tafolecimab group, as compared with −11.5% in the placebo group (ETD: −33.9% [95% CI: −42.2%, −25.7%]；P <0.0001). Meanwhile, tafolecimab treatment also led to a significant reduction in non-HDL-C and apolipoprotein B levels. The overall safety profile of tafolecimab was favorable, similar to that of previous studies of tafolecimab and other marketed PCSK9 inhibitors. Prof. Yong Huo, Principal Investigator of the CREDIT-4 study, Peking University First Hospital, stated, “The results of the CREDIT-4 study demonstrated that tafolecimab Q4W treatment significantly reduced LDL-C levels and improved other lipid parameters such as lipoprotein(a).The results were published in JACC:Asia, reflecting the excellent clinical research capabilities of Chinese researchers and providing high-quality medical evidence for the clinical treatment of hypercholesterolemia patients in China. As a self-developed PCSK9 inhibitor in China, tafolecimab can bring significant therapeutic benefits to Chinese hypercholesterolemia patients under the premise of favorable safety. I have strong confidence in the clinical application of tafolecimab and hope it could be launched to market to benefit Chinese hypercholesterolemia patients as soon as possible." Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: " In CREDIT-4, tafolecimab showed encouraging efficacy and favorable safety in Chinese patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia. The results were successfully published in an internationally renowned journal, which is a good recognition to the excellent scientific research capabilities of Chinese researchers, as well as the solid R&D execution of Innovent. As the pioneering PCSK9 inhibitor in China, tafolecimab's NDA is currently under review by the NMPA. I hope tafolecimab will be approved soon to provide more treatment options for Chinese hypercholesterolemia patients.” About Hypercholesterolemia In recent years, the blood lipid level of the Chinese population has gradually increased, and the prevalence of dyslipidemia has increased significantly with an overall prevalence of 40.4% in Chinese adults. The increase of serum cholesterol level in the population will lead to an increase of about 9.2 million cardiovascular disease events in China between 2010 ~ 2030. Dyslipidemia, characterized by elevated LDL-C or TC, is an important independent risk factor for atherosclerotic cardiovascular disease. At present, the disease management of hyperlipidemia in China is not optimistic. According to the 2020 China Cardiovascular Health and Disease Report, the diagnostic, treatment and control rate of dyslipidemia in Chinese adults remain low. The percentage of patients with dyslipidemia who met the LDL-C reduction goal is even more alarmingly low. Current lipid-lowering therapies do not meet the clinical needs in patients with hyperlipidemia. Anti-PCSK9 monoclonal antibody has a mechanism of action different from existing lipid-lowering drugs and can effectively reduce LDL-C levels, which is expected to provide a better treatment option for Chinese patients with hypercholesterolemia. About Tafoleicmab (PCSK9 inhibitor) Tafolecimab, independently developed by Innovent, is an lgG2 fully human monoclonal antibody that can specifically bind to PCSK9 and reduce LDL-C level by inhibiting PCSK9-mediated low-density lipoprotein receptor (LDLR) endocytosis, subsequently enhancing the clearance of LDL-C, resulting in a reduction in LDL-C level. About CREDIT Pivotal Studies CREDIT-1 is a randomized, double-blind, placebo-controlled phase 3 clinical study to assess the efficacy and safety of IBI306 in Chinese patients with non-familial hypercholesterolemia (hypercholesterolemia with cardiovascular risk) (ClinicalTrials.gov, NCT04289285). The primary efficacy measure was the percentage reduction from baseline in LDL-C after 48 weeks of treatment. CREDIT-2 is a randomized, double-blind, placebo-controlled phase 3 clinical study to evaluate the efficacy and safety of IBI306 in Chinese subjects with heterozygous familial hypercholesterolemia (ClinicalTrials.gov, NCT04179669). The primary efficacy endpoint was the percentage reduction from baseline in LDL-C after 12-week treatment. CREDIT-4 is a randomized, double-blind, placebo-controlled phase 3 clinical study to assess the efficacy and safety of IBI306 in Chinese patients with hypercholesterolemia (including non-familial hypercholesterolemia and heterozygous familial hypercholesterolemia) (ClinicalTrials.gov, NCT04709536). The primary efficacy measure was the percentage reduction from baseline in LDL-C after 12 weeks of treatment. The main results of the CREDIT-1 study were presented in a poster at the American Heart Association (AHA) Scientific Sessions 2022[i], and the study will be published in a peer-reviewed academic journal soon. The main results of the CREDIT-2 study were presented in a conference poster at the American College of Cardiology (ACC) Scientific Sessions 2022[ii], and the study was published in BMC Medicine[iii]. The CREDIT-4 study was published online in JACC: Asia in July 2023[iv]. 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 for the treatment of cancer, autoimmune disease, metabolic disorder 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 9 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab injection), SULINNO® (adalimumab injection), HALPRYZA® (rituximab injection), Pemazyre® (pemigatinib oral inhibitor), olverembatinib(BCR ABL TKI), Cyramza® (ramucirumab), Retsevmo® (selpercatinib) and FUCASO® (Equecabtagene Autoleucel). An additional 2 assets are under NMPA NDA review, 6 assets are in Phase III or pivotal clinical trials, and 18 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, Roche, 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. Disclaimer: Innovent does not recommend any off-label usage. 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. 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, 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. Contact Media： E-mail：[email protected] Tel：+86 512-69566088 Investors： E-mail：[email protected] Tel：+86 512-69566088 Reference [i] Huo Y, Li Y, Zhang P, et al. Efficacy and Safety of Tafolecimab in Chinese Patients With Non-Familial Hypercholesterolemia (CREDIT-1): A 48-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial. Circulation. 2022;146(Suppl_1):10111. [ii] Zhou Y, Chai M, He Y, et al. Efficacy and Safety of Tafolecimab in Chinese Patients with Heterozygous Familial Hypercholesterolemia (CREDIT-2): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial. ACC. 2022;1188-005/5. [iii] Chai M, He Y, Zhao W, et al. Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2). BMC Med. 2023;21(1):77. Published 2023 Feb 28. [iv] https://doi.org/10.1016/j.jacasi.2023.04.011

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