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NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis)

NAFLD is a common liver disease with extensive fat build up in liver. Some patients continue to progress to more severe liver injuries, manifested by lobular inflammation, hepatocyte damage and fibrosis, as knowns as NASH. Abnormal liver fat accumulation by itself is associated with greater risks of cardiovascular diseases. If untreated, NASH can progress to more serious, life-threatening clinical conditions, including cirrhosis, hepatocellular carcinoma, liver transplantation, and even death.

The growing prevalence of NAFLD and NASH parallels with the dramatic rise in population of obesity and metabolic syndrome in global and China. One study estimated 25% people worldwide have NAFLD, and by 2030 there will be 27 million and 48 million NASH patients in China and U.S., respectively. Treatment for NASH is limited to life style modification. No pharmacological treatment has been approved in major markets yet.

Diabetes

Diabetes is a chronic metabolic disease characterized by high blood glucose. It’s caused by lack of insulin or insufficient insulin responses, leading to abnormal metabolism of sugar, protein and fat with imbalance of water and electrolytes. If uncontrolled, diabetes could result in life threatening conditions like ketoacidosis, and chronic microvascular complications as well as increased cardiovascular risks. Diabetes associated with genetic susceptibility, environmental factors and life style changes.

According to the International Diabetes Federation (IDF), the number of diabetes patients in the world was 463 million (prevalence 9.3%) in 2019, and is estimated to increase to 578 million (+24.8%) in 2030 and 700 million (+51.2%) in 2045. In terms of health care spending, about $760 billion was spent in 2019, which is expected to rise to $825 billion in 2030 and $845 billion in 2045. Diabetes has become one of the fastest growing health problems in the 21st century.

Obesity

Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health. A body-mass-index (BMI, defined as the body mass divided by the square of the body height) of more than 25 is considered overweight and a BMI of more than 30 is considered obese according to WHO classification. East Asian population have lower cutoffs. Some of the known causes of obese are diet, physical activity, life styles, genetic susceptibility, and endocrine disorders.

Globally, a total of 1.9 billion and 609 million adults were estimated to be overweight and obese in 2015, respectively, representing approximately 39% of the world’s population. The prevalence of overweight and obese increased 50% and 80% over the past 40 years. Excessive body weight has a strong link to many diseases and conditions, particularly cardiovascular diseases, type 2 diabetes mellitus, obstructive sleep apnea, certain types of cancer, osteoarthritis and asthma. As a result, obesity has been found to reduce life expectancy. Weight loss through lifestyle interventions, including diet restriction and physical exercise are often successful at the given period, but research shows that maintaining that weight loss over the long term proves to be rare. Medications with safe and durable efficacy are highly desired.

Dyslipidemia

Dyslipidemia,an abnormality in blood lipids consisting of high levels of low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglyceride (TG) or low levels of high density lipoprotein cholesterol (HDL-C) singly or in combination, is an important modifiable risk factor for the development of atherosclerosis and cardiovascular disease (ASCVD). The World Health Organization estimates that dyslipidemia is associated with more than 50% of global cases of ischemic heart disease, and over 4 million deaths per year. About 80% of lipid disorders are related to diet and lifestyle, with the remainder being familial. The overall prevalence of dyslipidemia in Chinese adults is as high as 40%.

Statins are the most important drugs for these diseases. However, up to 40% of patients still have residual cardiovascular risk. In recent years, new targets for lipid-lowering therapy have become a research hotspot. With the development of new lipid-lowering drugs, the treatment of residual risk will be further improved, and eventually reduce the risk of ASCVD events.

Immune-related diseases

The immune system is the foundation of our heathy lives, to defend against external pathogens and maintain internal homeostasis.

Many diseases stem from an imbalance in immune system:

  • • Infection: invasion by harmful bacteria, viruses and other pathogens
  • • Allergy: overactivation to environmental antigens
  • • Autoimmune diseases: overactivation to self-antigens
  • • Cancer: failure of clearance of emerging and metastatic cancer cells

There are more than 100 different autoimmune diseases and even more different cancers that affect people around the world, and many of them have no effective treatments yet. Eccogene immune programs emerges by de novo target discovery efforts based on the internal immunometabolism platform, as well as collaborative partnership.

Osteoarthritis

Osteoarthritis (OA) is a degenerative condition characterized by focal areas of loss of articular cartilage within the synovial joints. It impacts the quality of life from mild to severe, when it progresses from intermittent pain to chronic pain with progressive irreversible structural damage and progressive loss of function. It’s also associated with all cause mortalities likely due to reduced physical activities and self-management of other comorbidities. The prevalence of OA increases along with increasing aging and obese populations. It is estimated that 25% of male and 30% of female are affected in the 45-64 year range, and the proportion increases to 58% for men and 65% for women, respectively.

There is no cure for osteoarthritis. The majority of current treatment options which aim to reduce symptoms and improve the quality of life are lacking in one or both aspects. More than half of patients with osteoarthritis cannot achieve sufficient analgesic effect with existing treatment options. Some comorbidities constitute contraindications to using OA therapies such as non-steroidal anti-inflammatory drugs (NSAIDs). Thus, new therapies with superior efficacy and safety profile are highly desired.