clinical

RP901

osteoarthritis (OA) refers to a degenerative disease with joint pain as the main symptom caused by multiple factors such as joint cartilage fibrosis, chapping, ulcer and loss. According to the World Health Organization, 355 million people worldwide suffer from osteoarthritis. With the advent of an aging society, under the influence of obesity, diabetes and environmental factors, more than 100 million people in China suffer from osteoarthritis. The global market size of osteoarthritis pain drugs reached 54.3 billion CNY in 2019 and is expected to reach 80.4 billion CNY in 2026, with a compound annual growth rate (CAGR) of 5.7%. RP901 is a new chemical entity discovered and developed by Risen, which plays the role of bone protection and osteoarthritis improvement through rapid transformation in vivo, and is intended to be developed as FIC oral drug for the treatment of osteoarthritis (OA). The results of pre-clinical efficacy study showed that it had clear effects on bone protection and OA improvement. Preclinical pharmacokinetic studies showed that RP901 has a high oral bioavailability in rats and monkeys, and isotope labeling studies showed that RP901 has a good distribution in targeted joint organs. Preclinical safety and Phase 1 clinical trial results indicate that RP901 has a good safety profile. Core compound patent application for this product in many countries and regions around the world has been authorized. The company has global rights of RP901 in manufacturing, using, selling, supply, export, import and other development and commercialization.

RP902

RP902 tablets is a deuterated small molecule drug discovered and developed by Risen for the treatment of Alzheimer's disease (AD). There are currently about 9 million AD patients in China, and it is predicted that the number will reach 21 million by 2050. However, the market demand for AD drugs is far from being met, among which, the clinical development of non-deuterated homotaurine as a potential AD drug has progressed to phase III, and the results show that the cognitive ability of ApoE4 homozygous carriers is more significantly improved after non-deuterated homotaurine treatment. With understanding to the adverse events such as nausea, vomiting and weight loss observed in previous non-deuterated homotaurine clinical trials, the Risen R&D team developed the pro-drug RP902. RP902 features two deuterium (D / 2H) replacement of hydrogens (1H) in the structure as optimization. In vivo, it can be converted into deuterated homotaurine, which has slow bond breaking rate, so that change its pharmacokinetic properties and improving its clinical performance. Preclinical pharmacological studies showed that RP902 could significantly improve image recognition memory, spatial memory and long-term memory impairment in AD model mice. The damage of neuronal cells and dendrites in hippocampus and cerebral cortex of model mice was significantly improved, and synaptic plasticity was improved. The deposition of Aβ in brain and the (insoluble) levels of Aβ1-40 and Aβ1-42 in brain of model mice were decreased.

RP903

RP903 is a stable isotope replaced small molecule drug discovered and developed by Risen. It is an inhibitor targeting PI3Kα for advanced malignant solid tumors with PIK3CA mutation. RP903 has applied for patent protection in several countries/regions (CN201910447749.3, US 62/994,378), obtained NMPA and FDA Phase I clinical approvals in May and June 2022, respectively, and is currently in Phase I clinical trials cooperated with TopAlliance, Shanghai. In pre-clinical studies, RP903 was compared with Alpelisib head-to-head and the results showed that RP903 demonstrated similar efficacy to Alpelisib in human breast cancer cell MCF-7 and BT-474 xenografted tumor mouse models. In addition, RP903 has also shown great efficacy in several animal models of cervical cancer and kidney cancer.

PI3K/Akt/mTOR Pathway

3 sub-types of PI3K

• PAM pathway regulates the survival, proliferation, differentiation and apoptosis of tumor cells • PI3K in PAM channel can be divided into types Ⅰ, Ⅱ, and Ⅲ • The mutation of p110α encoded by the PIK3CA gene causes the PI3K kinase to be continuously activated • This mutation is widespread in malignant solid tumors.