CVI Pharmaceuticals Advances Oral Small-Molecule PCSK9 Inhibitor CVI-LM001 into Phase II Clinical Trials
CVI Pharmaceuticals
Small Molecule Oral Drug Developer
VCBeat (WeChat Official Account: vcbeat) has learned that CVI Pharmaceuticals Limited (“CVI Pharmaceuticals”) will participate in the American Heart Association (AHA) and the American Association for the Study of Liver Diseases (AASLD) conferences scheduled for early November 2020, where it will officially release the preclinical pharmacodynamic study results and Phase I clinical trial findings of its Class 1 oral small-molecule innovative lipid-lowering drug, CVI-LM001 (“LM001”).
CVI Pharmaceuticals is a biopharmaceutical company focused on the research and development of innovative drugs for cardiovascular and hepatic metabolic diseases. Its most advanced project, LM001, is currently in Phase II clinical trials. The company has established modern R&D centers, as well as preclinical drug development and clinical research management teams, in California, USA, and Shanghai.
How Important Is Lowering Blood Lipids, Exactly?
The National Medical Products Administration (NMPA) points out in its new technical guidelines for clinical trials of drugs treating lipid metabolism disorders that the research and development of drugs targeting lipid metabolism disorders is of great significance to the prevention and control of cardiovascular diseases in China.
Why? Let’s examine a set of data.
According to the results of chronic disease surveillance studies, the prevalence of hyperlipidemia in China exceeds 10%, which translates to approximately 100 million individuals affected by the condition.
With the intensifying aging of the population and increased consumption of animal fats, the number of patients with hyperlipidemia in China has been steadily rising, with an annual growth rate of approximately 10%. The mortality rate from diseases caused by hyperlipidemia exceeds 30%.
According to WHO statistics, in 2018, deaths from cardiovascular and cerebrovascular diseases accounted for 31.2% of all global deaths, twice the number of cancer-related deaths.
Deeply aware of the critical responsibility that lipid-lowering therapy bears for national and public health, Dr. Liu Jingwen, who has dedicated over two decades to cardiovascular diseases and hepatic lipid metabolism, founded CVI Pharmaceuticals in 2007. Adhering to the principle of matching experts with specific conditions, CVI Pharmaceuticals’ core team comprises industry leaders specializing in the treatment of disorders of lipid metabolism.
Dr. Liu Jingwen, the company’s founder, is a renowned international academic leader in the field of cardiovascular disease research and has co-authored a paper on the molecular mechanisms by which berberine lowers blood lipids, published in Nature Medicine. The company has also established a core team for medical affairs and clinical operations, featuring experts with decades of deep industry experience in cardiovascular disease, lipid metabolism, and GMP-compliant pharmaceutical manufacturing. This team offers unique insights into strategies for entering the lipid-lowering therapy market.
Starting from molecular mechanisms, CVI Pharmaceuticals targeted the low-density lipoprotein receptor (LDL-R) and PCSK9, which plays a crucial regulatory role in LDL-R protein levels. The company established more than ten in vitro and in vivo screening platforms, synthesized a library of over 300 compounds with novel structures, and identified its current lead candidate, CVI-LM001 (hereinafter referred to as “LM001”). Through cross-validation across these platforms, the company focuses on disorders of lipid metabolism, committed to bringing benefits to patients with hyperlipidemia in China.
Investment firms sharing the same vision as CVI Pharmaceuticals quickly responded. Morningside Venture Partners collaborated with CVI Pharmaceuticals from the outset, providing Series A startup funding. Subsequently, pharmaceutical-focused investors such as Shanghai Zhangjiang Venture Capital, Jiangsu Jiequan Lize Health Industry Venture Investment Fund, and Baifu (Changzhou) Healthcare Investment Fund joined in succession, facilitating CVI Pharmaceuticals’ development of innovative small-molecule drugs for lipid-lowering therapy.
Of course, in addition to CVI Pharmaceuticals’ own robust research capabilities, the high-potential market space for lipid-lowering therapies has also deeply attracted investors’ attention.
Based on the market size of domestic lipid-lowering drugs in 2016 and the compound annual growth rate over the past decade, the market is projected to exceed RMB 40 billion by 2020. On a global scale, the worldwide market for lipid-lowering drugs was valued at USD 19.2 billion in 2017 and is expected to reach USD 23.7 billion by 2025.
In this vast market, common statins account for approximately 85% of the lipid-lowering drug market. However, even in the United States, more than 40% of high-risk ASCVD patients fail to achieve their lipid-lowering targets after receiving high-intensity statin therapy; in Asia, this figure exceeds 50%. Patients in China exhibit poorer tolerance to high-dose statins, with a higher incidence of side effects compared to European patients.
Among non-statin lipid-lowering agents, the main options in China are cholesterol absorption inhibitors and traditional Chinese medicine (TCM) single-ingredient or compound formulations. Abroad, the primary agents are cholesterol absorption inhibitors (ezetimibe) and Nexletol (an ATP citrate lyase inhibitor), which was newly launched this year. In addition, PCSK9 monoclonal antibodies have recently been marketed; while they demonstrate significant efficacy, their requirement for injectable administration results in inconvenience and high costs for the broad population of patients with hyperlipidemia, leaving an unmet clinical need.
Therefore, both patients and clinicians are eagerly awaiting the emergence of a novel, conveniently administered, domestically produced small-molecule lipid-lowering drug. At this juncture, CVI Pharmaceuticals has entered the public spotlight with LM001, a synthetic PCSK9 inhibitor.
The founder’s vision determines the enterprise’s starting point. Dr. Liu Jingwen possesses profound expertise in the fundamental research of cholesterol anabolic metabolism and artificial intervention, leading CVI Pharmaceuticals to target key pathways in lipid metabolism. Through screening 300 potential novel-structure compounds developed in-house, the company identified LM001.
LM001 embodies the key characteristics envisioned by the company’s founders for a lipid-lowering agent, with its profile initially demonstrated in Phase I clinical trials completed by Saiwei Ai. According to VCBeat, results from four Phase I clinical trials indicate that LM001 not only exhibits excellent safety, tolerability, and favorable pharmacokinetic properties, but also shows promising efficacy in preliminary Phase Ib studies, positioning it as a potential standout among non-statin oral small-molecule drugs.
More importantly, CVI Pharmaceuticals has already obtained key proof-of-mechanism data from the Phase I clinical trial of LM001, demonstrating its ability to reduce PCSK9 protein levels in the blood of both healthy subjects and individuals with hyperlipidemia, which is consistent with preclinical screening results. Dr. Liu Jingwen revealed that CVI Pharmaceuticals is continuing to conduct in-depth research on the relevant molecular mechanisms, and the exploration and validation of these mechanisms will further substantiate the advantages of LM001 in lipid-lowering therapy.
Currently, the first patient with hyperlipidemia has been enrolled in the multicenter Phase II clinical trial of CVI-LM001 tablets, a randomized, double-blind, multiple-dose, placebo-controlled study evaluating efficacy and safety in subjects with hypercholesterolemia. This study aims to further assess the safety and efficacy of oral CVI-LM001 in Chinese subjects with hyperlipidemia.
CVI Pharmaceuticals' R&D Pipeline Layout
In addition, SWE is concurrently conducting a Phase II clinical trial of LM001 in the United States to evaluate its lipid-lowering effects in patients with fatty liver disease, and advancing research on CVI-LM002 (hereinafter referred to as “LM002”) for the treatment of NASH and obesity.
Since its inception, CVI Pharmaceuticals has actively prioritized intellectual property protection. Its lipid-lowering technology has secured comprehensive patent coverage, encompassing the chemical structures of CVI-series compounds, their synthesis methods, and indications. Currently, core patents have been granted and entered key markets—including the European Union, the United States, Japan, and China—via the Patent Cooperation Treaty (PCT).
Dr. Liu Jingwen stated that the small molecule CVI-LM001 holds significant commercial potential, and its patent layout and successful registration will establish technical barriers for CVI Pharmaceuticals, enabling it to maintain its leading position in the industry.
Furthermore, benefiting from national support and encouragement for drug development targeting lipid metabolism disorders, CVI Pharmaceuticals has cultivated deep expertise in the field of lipid-lowering therapies for many years, securing multiple grants from both national and local governments, including rolling funding support from the National Major Special Project for New Drug Innovation during the 11th and 12th Five-Year Plan periods.
CVI Pharmaceuticals is gaining strong momentum, ramping up efforts to advance the clinical trials of its small-molecule candidate LM001 and launching new R&D pipelines, with the aim of taking a leading position in the field of hyperlipidemia treatment.
Clinical Trials
CVI Pharmaceuticals will rapidly complete the Phase II clinical trial of LM001 for the treatment of hyperlipidemia in China and advance to Phase III clinical trials, while simultaneously completing the Phase II clinical trial of LM001 in combination with statins.
New Indication Expansion
CVI Pharmaceuticals will conduct a Phase II clinical trial in the United States to evaluate lipid-lowering therapy in patients with fatty liver disease, and will actively explore other metabolic disorders.
In the Area of New Small-Molecule Drug Research
CVI Pharmaceuticals will continue to advance the development of CVI-LM002 and other innovative drugs targeting metabolic disorders.