Innovent Announces IBI306 (anti-PCSK-9 antibody) Meets the Primary Endpoint in a Phase 3 Clinical Study for Chinese Heterozygous Familial Hypercholesterolemia

Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, announces today that the primary endpoint was met in the phase 3 study CREDIT-2 of recombinant fully human anti-PCSK-9 monoclonal antibody (R&D code: IBI306, independently developed by Innovent) for the treatment of Chinese heterozygous familial hypercholesterolemia (HeFH).

The analysis showed that after 12 weeks of continuous treatment with IBI306 in Chinese patients with heterozygous familial hypercholesterolemia who have been previously treated with statins and/or ezetimibe, their low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced compared with the placebo arm. Throughout the study, IBI306 demonstrates a favorable safety profile, similar to the reported safety profiles of other marketed PCSK-9 inhibitors.

The principal investigator of the CREDIT-2 study, Prof. Yujie Zhou, Vice President of Anzhen Hospital, from the Capital Medical University stated, "Although the prevalence of familial hypercholesterolemia is relatively low, due to the large population in China, the absolute number of patients still ranks among the highest in the world. Heterozygous patients often progress rapidly with an early onset, resulting in the significant increase of the serum total cholesterol (TC) and low density lipoprotein (LDL-C) levels. Patients may experience severe atherosclerotic cardiovascular disease (ASCVD) or even death in early and middle ages. Recently, PCSK-9 inhibitors, as a new class of effective therapy to treat familial hypercholesterolemia, have been recommended by the US, EU and China guidelines. Although there are imported PCSK-9 inhibitors on the China market, there is a lack of evidence in Chinese heterozygous familial hypercholesterolemia. We are very pleased to announce that as one of the key registration studies of a Chinese innovative anti-PCSK-9 monoclonal antibody IBI306, CREDIT-2 has met its primary endpoint. For the first time, Chinese researchers have confirmed that anti-PCSK-9 monoclonal antibody can significantly reduce LDL-C levels with an overall favorable safety profile in such patient population through a randomized, double-blind, controlled study. This study provides new high-quality clinical evidence for the treatment of Chinese heterozygous familial hypercholesterolemia population."

Dr. Lei Qian, Executive Director of Medical Sciences and Strategies of Special Diseases of Innovent, stated: " There remains a great unmet medical need in Chinese patients with heterozygous familial hypercholesterolemia. As a novel PCSK-9 inhibitor developed by Innovent with independent intellectual property rights, previous study results showed that IBI306 could effectively reduce TC and LDL-C levels in patients with hypercholesterolemia, and the success of CREDIT-2 further validated the efficacy of IBI306 and was also a key step in the registration of IBI306. We hope to provide clinicians with an effective, safe, and more accessible treatment option through innovative development strategies and solid research design, so as to achieve the goal of benefiting more patients with hypercholesterolemia. I am confident and looking forward to the results of other pivotal registrational studies of IBI306."

About CREDIT-2 study

The CREDIT-2 study is a randomized, double-blind, placebo-controlled phase 3 study to evaluate the efficacy and safety of IBI306 in Chinese subjects with heterozygous familial hypercholesterolemia (ClinicalTrials.gov, NCT04759534). A total of 148 eligible patients were enrolled. The primary efficacy endpoint was the percentage reduction from baseline in LDL-C after 12-week treatment.

About Heterozygous Familial Hypercholesterolemia (HeFH)

In recent years, the blood lipid level of Chinese population has gradually increased. As a result, the prevalence of dyslipidemia has increased significantly. The overall prevalence of dyslipidemia in Chinese adults is as high as 40.4%. The increase of serum cholesterol level in the population will lead to an increase of about 9.2 million cardiovascular diseases in China from 2010 ~ 2030. Dyslipidemia characterized by elevated LDL-C or TC is a well-established risk factor for atherosclerotic cardiovascular disease

Familial hypercholesterolemia, the main cause of premature coronary heart disease, refers to elevated blood cholesterol due to genetic abnormalities, which is characterized by familial aggregation and autosomal dominant inheritance. The vast majority of patients with familial hypercholesterolemia are caused by single allele mutation and are classified as heterozygous familial hypercholesterolemia. The incidence of HeFH is about 1 in 500 to 1 in 200.

In 2018, the Chinese Expert Consensus on Screening, Diagnosis and Treatment of Familial Hypercholesterolemia in China recommended statins as the first line of treatment and ezetimibe as the first choice of combination therapy. PCSK-9 inhibitors may be administered to patients with familial hypercholesterolemia who did not achieve favorable response after treated with statins and/or ezetimibe.

About IBI306 (Anti-PCSK-9 antibody)

IBI306, developed by Innovent, is an lgG2 monoclonal antibody that can specifically bind to PCSK-9 and reduce LDL-C level by inhibiting PCSK-9-mediated low-density lipoproteinreceptor (LDL-R) endocytosis, subsequently enhancing the clearance of LDL-C, resulting in the reduction of the LDL-C level. At present, a phase I clinical study in healthy subjects and a phase IIa clinical study in subjects with hypercholesterolemia have been completed for IBI306, demonstrating good efficacy and favorable safety. CREDIT-2 is the first phase 3 study, and several clinical studies are still ongoing to assess the efficacy and safety of IBI306 in patients with various types of hypercholesterolemia.

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, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China 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 25 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) and Pemazyre® (pemigatinib oral inhibitor) – officially approved for marketing, 1 asset's NDA under NMPA review, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 14 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, Adimab, Incyte, MD Anderson Cancer Center, Hanmi 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.