1. Chronic hepatitis B treatment

1.1 Introduction

     WHO estimated that 296 million people were living with chronic hepatitis B infection in 2019, with 10 to 30 million new cases worldwide each year. In patients with chronic hepatitis B, the viruses always exist in the liver. Although the virus will not directly cause damage to the liver, it stimulates the immune cells to attack the liver cells, which will cause severe liver diseases and increase risk of developing cirrhosis and liver cancer.

     Current approved drugs for Hepatitis B virus (HBV) can be divided into two classes: nucleoside/nucleotide analogs (NAs) and interferon-α (IFN-α). NAs can effectively inhibit HBV replication, and are widely used because of their good safety and convenient oral administration. However, NAs drugs cannot eradicate HBV covalently closed circular DNA (cccDNA), which is the transcription template of HBV, must be taken for a long time, and there is still a risk of recurrence after drug withdrawal. IFN-α regulates the immune system to control HBV. However, due to serious side effects, higher price, and injection administration, the patient acceptance of IFN-α is low.

1.2 Unmet medical needs

     Due to the characteristics of HBV, there are still no drugs which can achieve the ultimate goal of "complete cure" in current medical technology.Therefore, new drugs for the treatment of hepatitis B are still being developed to achieve "functional cure" as the goal to prevent the liver from continuing to be in a state of inflammation and reduce the incidence of liver fibrosis, cirrhosis, and liver cancer.

     The best indicator for functional cure is the loss of HBsAg (surface antigen) and HBsAb (surface antibody) positive. However, the probability of HBsAg loss after long-term use of NAs drugs or IFN-α is less than 8%.

     Another indicator for functional cure is HBeAg seroconversion (HBeAg loss and HBeAb positive), which represents HBV being inactivated and its infectivity being greatly reduced. Therefore, the risk of liver cirrhosis and liver cancer is reduced. The HBeAg seroconversion rate is only 20-30% after long-term treatment with NAs or IFN- α.

　　The current challenges of hepatitis B treatment include long-term medication, drug resistance of HBV, viral relapse, and liver inflammation which increases risk of liver cirrhosis and liver cancer. Botanical new drug BEL-X has been developed aiming at improving the HBeAg seroconversion in shorter treatment period. If the efficacy of BEL-X can be proven in clinical trials, it will offer big benefits not only to chronic hepatitis B patients but also to the cost of health care.

 1.3 MOA of botanical new drug for HBV treatment

　　   It has been found that botanical new drug BEL-X blocks viral attachment in cell-based infection system, and, therefore, reduces viral entry amount into hepatocytes.

　　  Using the HBV stable expression cell platform, NAs add-on BEL-X treatment can effectively inhibit both HBV replication and the production of HBe and HBs antigens. We are planning a phase II trial of, using NA add-on BEL-X to treat chronic hepatitis B patients with HBeAg positive and HBeAb negative, to explore the potential improvement of efficacy and reduction of treatment period.

２.  Tumor related diseases: cancer cachexia

2.1Introduction

　　  According to World Cancer Research Fund International there are more than 18 million cancer patients in the world in 2020, with 9 million new cases every year. More than 50% of cancer patients have cachexia symptoms, which are the direct cause of death of 20-40% of terminal cancer patients.

　　The symptoms of cancer cachexia are diverse, including weight loss, severe muscle atrophy, decreased activity, fatigue, anorexia, and etc., which in turn affect the quality of life of cancer patients and also cause family care problems. The overall mechanism of cancer cachexia is not yet fully understood. Hormones secreted by tumor cells trigger systemic inflammatory responses, causing metabolic dysfunction, which in turn increases liver oxidative stress and loss of muscle and fat tissue, which are the main pathogenic factors.

2.2Unmet medical needs

     Although there are many patients affected by cancer cachexia, the FDA has not yet approved any drug for the disease. The current treatment of cancer cachexia mainly provides progesterone or steroids to increase patient's appetite. However, the side effects caused by the above two categories of drugs include edema, insomnia, immune suppression, muscle weakness, and etc., which are very detrimental to the quality of life and survival of patients with advanced cancer.

     Botanical new drug BEL-X focuses on both "maintaining body weight and muscle mass/strength" and "increasing the tolerance of chemotherapy drugs", and thus can improve the quality of life of cancer cachexia patients.

2.3MOA of botanical new drug for cancer treatment

       Botanical new drug BEL-X, offers multiple mechanisms, including reducing oxidative stress and regulating inflammatory responses. In various tumor animal models, botanical new drug BEL-X can inhibit tumor size, improve muscle loss, maintain body weight, and increase both survival rate and survival period. Phase II clinical trials of BEL-X to treat cancer cachexia have been in pipelines.

       In the phase I trial of botanical new drug BEL-X has been obtained that the preliminary efficacies include maintaining body weight, improving quality of life, and increasing survival periods for solid tumor patients.

    Phase II clinical trials of cancer cachexia and different types of cancers have been planned in pipelines to demonstrate botanical new drug BELX’s efficacy and maximize its commercial values.