Zhongsheng Ruichuang Focuses on Novel Drug Development in Liver and Respiratory Diseases, with Anti-Influenza Candidate in Phase II Clinical Trials

Deloitte’s 2019 report, “2019 Global Life Sciences Outlook,” reveals that the return on innovation from drug R&D for 12 large biopharmaceutical companies fell to its lowest level in nine years, reaching just 1.9% in 2018, significantly below the 10.1% recorded in 2010. The cost of bringing a single drug to market reached a record high of $2.168 billion in 2018.

Innovative drug development is perpetually a sunrise industry, yet each new drug development endeavor is a high-stakes gamble. Consequently, mitigating the risks associated with innovative drug R&D has become a key focus for pharmaceutical companies. Establishing subsidiaries to diversify R&D risk represents a viable strategy.

In October 2018, Guangdong Zhongsheng Pharmaceutical Co., Ltd. (hereinafter referred to as “Zhongsheng Pharmaceutical”) established its innovative R&D holding subsidiary, Guangdong Zhongsheng Ruichuang Biotechnology Co., Ltd. (hereinafter referred to as “Zhongsheng Ruichuang”). Leveraging collaborations with strategic partners and research institutions, and relying on its in-house R&D team and globally leading technology platforms for NASH and ANIT-PBC, the company focuses on developing major novel drug candidates with significant market potential.

Dr. Liu Dongzhou, President of Zhongsheng Ruichuang, stated: “Zhongsheng Pharmaceutical established Zhongsheng Ruichuang through non-monetary contributions, which facilitates the attraction of strategic financing, shared R&D investment risks, and more effective advancement of innovative drug development. This approach supports the company’s sustained, rapid, long-term, and healthy growth, thereby promoting the achievement of its strategic objectives.” To date, multiple innovative drugs developed by Zhongsheng Ruichuang, including those for non-alcoholic steatohepatitis (NASH) and respiratory diseases, are at various stages of clinical and preclinical research.

Currently, Zhongsheng Ruichuang has six R&D projects: ZSP1601, ZSP0678, ZSYM008, and RCYM001 in the field of liver diseases, and ZSP1273 and ZSP1603 in the field of respiratory diseases.

Dr. Liu introduced that, based on multifaceted considerations, ZR Pharma has concentrated its projects in the fields of liver disease and respiratory disorders. In 2015, Zhongsheng Pharmaceutical entered into a strategic agreement with WuXi AppTec, signing multiple collaborative R&D agreements for innovative drug projects, primarily focusing on respiratory diseases, oncology, and non-alcoholic steatohepatitis (NASH). Among these, the R&D pipelines in the respiratory and liver disease sectors have advanced rapidly, with several drugs obtaining Investigational New Drug (IND) approvals for clinical trials.Zhongsheng Pharmaceutical has transferred these Class I new drugs to its innovative biopharmaceutical holding subsidiary, Zhongsheng Ruichuang, to accelerate drug R&D and product launches, thereby providing patients with safer and more effective pharmaceutical products.

Furthermore, Dr. Liu noted that there is a substantial unmet clinical need in the fields of hepatology and respiratory medicine, particularly for non-alcoholic steatohepatitis (NASH) and influenza.

It is estimated that the global prevalence of NASH ranges from 3% to 5%, with approximately 15% to 25% of patients progressing to cirrhosis. By 2025, NASH is projected to become the leading indication for liver transplantation. Despite the urgent unmet medical need, no drugs have yet been approved for the treatment of NASH, making the NASH therapeutic landscape a promising new frontier in pharmaceutical R&D.

There is also a substantial unmet medical need in the field of influenza. The World Health Organization (WHO) estimates that influenza causes 3 to 5 million cases of severe illness annually, resulting in 250,000 to 500,000 deaths. In the United States alone, the annual economic burden of influenza amounts to $80 billion, with the adult influenza therapeutics market nearing $10 billion. China is a high-prevalence region for influenza, with tens of millions of cases reported each year.

However, existing influenza medications struggle to cope with the highly mutable influenza virus, and vaccine efficacy is often compromised by viral immune escape. Therefore, there is an urgent need for novel anti-influenza drugs in the market to meet substantial clinical demand.

Zhongsheng Ruichuang has established a comprehensive drug development system encompassing bulk API synthesis, purification, scaled-up formulation manufacturing, clinical development, and regulatory registration.

Dr. Liu stated, “According to public information, most NASH drugs currently under development are in Phase I and Phase II clinical trials. The leading global NASH drug candidates include Intercept Pharmaceuticals’ obeticholic acid (for which a New Drug Application [NDA] was submitted to the U.S. FDA on September 27 for the treatment of liver fibrosis caused by NASH) and Genfit’s GFT-505, all of which have completed or entered Phase III clinical trials. Among domestic pharmaceutical companies, Zhongsheng Ruichuang is making relatively rapid progress in the development of new NASH drugs in China.”

ZSP1601 is the first Class 1 innovative drug approved for clinical trials in China for the treatment of NASH, featuring a novel mechanism of action and global independent intellectual property rights, and belongs to the First-in-class category.In preclinical studies, various animal models demonstrated that ZSP1601 was superior to the control product in ameliorating hepatic inflammation, hydropic degeneration, and necrosis, as well as improving fibrosis. Furthermore, the product exhibited potent anti-fibrotic effects and demonstrated an favorable safety and tolerability profile.

Meanwhile, ZSP1601 tablets are also the first domestic innovative drug project for the treatment of NASH to complete pharmacokinetic and safety clinical trials in healthy subjects, and plans are currently underway to initiate Phase Ib/IIa clinical trials.In addition, ZSP0678 tablets for the treatment of NASH have received a clinical trial approval notice; ZSP1603 for idiopathic pulmonary fibrosis is about to complete the Phase I clinical trial report.

ZSP1273 is a Class I innovative drug with a novel mechanism of action and independent global intellectual property rights, clinically indicated for the treatment of influenza A and human avian influenza.This drug is the first small-molecule RNA polymerase inhibitor approved for clinical trials in China for the treatment of influenza A. It features a novel and well-defined mechanism of action, high target selectivity, and potent in vitro activity. It is effective against multiple influenza A virus subtypes, including the legally notifiable Class B influenza A(H1N1) and avian influenza A(H7N9), as well as various oseltamivir-resistant strains of different subtypes.

ZSP1273 demonstrated efficacy in animal models with both prophylactic administration and therapeutic administration exceeding 48 hours, exhibiting a high safety profile and significant potential for clinical application. In Phase I clinical trials, ZSP1273 showed good safety and tolerability, along with favorable pharmacokinetic characteristics.

Currently, the multicenter Phase II clinical trial of ZSP1273 has been launched. “The Phase II clinical trial is being conducted at more than 20 clinical centers across 13 provinces and municipalities in China. The primary objective is to evaluate the safety and efficacy of ZSP1273 in treating adult patients with influenza A. The trial results are expected to be available in 2020, whereupon we will proceed with a comprehensive subsequent clinical development plan and, based on the clinical outcomes, prepare for the submission of a New Drug Application (NDA),” stated Dr. Liu.

R&D and management teams are critical factors determining project progress and success. The R&D team at Zhongsheng Ruichuang boasts extensive experience in both international and domestic drug development. According to Dr. Liu, “Over 70% of the R&D team members hold master’s degrees, and we have recruited doctoral and postdoctoral specialists in medicinal chemistry, pharmacology, toxicology, formulation, and clinical medicine.”

All members of the management team at Zhongsheng Ruichuang possess over 10 to 20 years of experience in drug research and development. Furthermore, the company has recruited numerous PhDs and postdoctoral fellows from prestigious universities and academic institutions, including the Shanghai Institute of Materia Medica, Peking University, and Sichuan University, to strengthen its R&D capabilities.

“Identifying, recruiting, effectively utilizing, and retaining talent” is the goal that Zhongsheng Ruichuang has been tirelessly pursuing. In June 2019, Zhongsheng Ruichuang appointed Dr. Liu Dongzhou, an overseas-returned Ph.D., as President, entrusting him with full responsibility for the company’s management and operations, product pipeline development, and other related work.

Dr. Liu holds a Ph.D. in Biochemical Immunology, completed postdoctoral training in Clinical Pharmacology, and earned an MBA in Finance. Previously, Dr. Liu worked for over 20 years at several large global multinational pharmaceutical and biopharmaceutical companies, serving in roles such as Supervisor, Director, and Head. He was a Senior Scientist and Department Head at Wyeth (now part of Pfizer) in the United States, and served as Project Leader and Chief Scientist at Forest Laboratories (now Allergan) in the United States. After joining GlaxoSmithKline (GSK) in the United States, he held positions as Director and Head of Clinical Development across the Product Development, Medical Affairs, and Clinical R&D departments. During his career, Dr. Liu participated in the research and development of more than ten blockbuster drugs.

Dr. Liu remarked, “I have been deeply impressed by the enthusiasm, investment, and innovative atmosphere surrounding domestic innovative drug R&D. China also offers robust policy support for new drug development, with significantly accelerated drug approval processes and regulatory authorities that are becoming more standardized, institutionalized, and internationalized. The overall ecosystem for innovative pharmaceuticals in China has truly moved and attracted me.”

When asked about his decision to join Zhongsheng Ruichuang, Dr. Liu stated, “During my interactions with Zhongsheng Pharmaceutical and Zhongsheng Ruichuang, I was deeply impressed by their perseverance and willingness to tackle challenges head-on. I also strongly endorse Zhongsheng’s diversified model for innovative drug development. In recent years, domestic new drug R&D has become increasingly internationalized. Zhongsheng Ruichuang boasts a highly competitive product pipeline. I hope to leverage my years of experience in new drug research and development to promote the healthy and sustainable growth of Zhongsheng Ruichuang’s R&D pipeline, accelerate drug commercialization, and help Zhongsheng Ruichuang secure a place in China’s and even the global pharmaceutical industry. At the same time, I aim to make a modest contribution to enabling local pharmaceutical companies to develop their own original modern medicinal products.”

Currently, Zhongsheng Ruichuang has filed over 80 PCT and Chinese invention patent applications, with multiple core patents granted in China, the United States, Japan, Europe, and other countries and regions.

Zhongsheng Ruichuang plans to initiate two to three Phase II/III clinical projects over the next three years or so, and will file an Investigational New Drug (IND) application with the U.S. FDA and conduct clinical studies based on the trial results. In the future, the company will also develop new projects, such as combination therapies, to meet the needs of diverse patient populations.

Dr. Liu stated, “Zhongsheng Ruichuang aims to become a leading, world-class, science-driven innovative pharmaceutical company in China. Upholding the principles of innovation, integrity, pragmatism, and patient-first, we are committed to developing innovative medicines that address unmet medical needs, providing patients with safer and more effective treatments. At the appropriate time, the company will consider initiating its initial public offering (IPO) process.”