Zhishan Weixin Biotech Files IPO Prospectus: Pioneering rAAV Gene Therapies for Genetic and Neurodegenerative Diseases

In 2008, the prestigious medical journal *N Engl J Med* (The New England Journal of Medicine) published study results demonstrating that researchers successfully treated several patients with congenital blindness using rAAV gene therapy, with therapeutic effects lasting for several years.

That same year, Dr. Dong Biao personally witnessed at the Children’s Hospital of Philadelphia (CHOP) in the United States how a blind child regained sight following rAAV gene therapy. “This deeply moved me,” Dr. Dong told VCBeat. “I sincerely hope this emerging therapy can benefit more patients.” His mentor, Professor Weidong Xiao, an internationally renowned rAAV expert, also placed high hopes on him, expecting Dr. Dong to return to China and develop the country’s first approved rAAV gene therapy drug.

Dr. Dong Biao earned his degree in Biology from The Chinese University of Hong Kong and subsequently conducted postdoctoral research at the Children’s Hospital of Philadelphia, University of Pennsylvania. During his postdoctoral tenure, his research group was led by Katherine High, the designer of the rAAV gene therapy used in this clinical trial and the leader behind the successful development of the world’s first rAAV-based gene therapy.

In 2014, Dr. Dong Biao returned to China and joined the State Key Laboratory of Biotherapy at West China Hospital, Sichuan University. At that time, China had no mature products in the field of rAAV gene therapies, nor did it have any clinical pipelines with significant progress. The laboratory at Sichuan University was poised to become an incubator for rAAV gene therapy development. Dr. Dong Biao serves as a researcher at both the State Key Laboratory of Biotherapy at West China Hospital, Sichuan University, and the National Clinical Research Center for Geriatric Diseases. He has led and participated in two National Key R&D Programs, three projects funded by the National Natural Science Foundation of China, and one industry-specific fund, all related to rAAV and genetic diseases. Prior to returning to China, he contributed to three rAAV research projects funded by the NIH.

rAAV gene therapies are not inexpensive. Abroad, a single rAAV gene therapy for congenital blindness can cost as much as $850,000, while treatment for spinal muscular atrophy (SMA) reaches up to $2.12 million per patient. “When targeting the Chinese market, the first priority for R&B Bio is to figure out how to reduce the operational costs of drug development and deliver gene therapies that are affordable for patients,” said Dr. Dong Biao.

Sichuan Real&Best Biotech Co., Ltd., operating under the brand name R&B Bio, is a biotechnology company founded by Dr. Dong Biao upon his return to China, specializing in research on recombinant adeno-associated virus (rAAV) gene therapies. The team comprises multiple experts with extensive experience in translating scientific achievements into industrial applications, as well as senior management professionals with rich industry expertise. Centered on the research and development and manufacturing of gene therapy recombinant viral vectors, the company integrates three core areas: basic research, drug development, and clinical-grade industrial-scale production of recombinant viruses, striving to become a leading enterprise in China’s rAAV gene therapy sector.

R&B Bio’s expert team comprises globally renowned neuroscientist Academician Ashley Bush, prominent clinical genetics diagnostic expert Alexander Valencia, and multiple specialists in viral drug industrialization, neurological disease development, hepatic metabolism, and immunology. The company’s technology transfer team members possess extensive experience in the biopharmaceutical sector, having participated in the R&D, manufacturing, and regulatory filing of numerous biologic drug projects.

Dr. Dong Biao, Founder of R&B Bio

Lei Peng, co-founder of the company, is an internationally renowned expert in neurodegenerative diseases. He is a Professor and Doctoral Supervisor at the Department of Neurology, West China Hospital of Sichuan University, and the State Key Laboratory of Biotherapy. He is also a recipient of the National Natural Science Foundation for Excellent Young Scholars. Dr. Lei has long been engaged in research on the molecular pathological mechanisms and prevention/treatment strategies for various cognitive disorders. Related strategies have entered clinical testing. He has published 44 papers in academic journals such as Nat. Med. and Mol. Psychiatry, and his research findings have been featured and commented on by journals including Nat. Med. and Nat. Rev. Neurol.

Another co-founder of the company is an expert in GMP production and management, with over 25 years of experience in preclinical research, clinical trial applications, production, and quality management of viral vaccines. He has established an industrialized technology platform for biological product manufacturing, centered on large-scale animal cell culture technology. He has completed preclinical studies for multiple vaccines, conducted process development for viral vaccines, and carried out research on scale-up from laboratory to pilot and production scales, securing clinical trial approvals for more than ten new drug products.

“There are currently over 7,000 types of genetic diseases in humans. Among them, hemophilia is one of the most prevalent in terms of patient population. However, the development of innovative drugs for hemophilia faces numerous technical challenges,” Dr. Dong Biao told VCBeat. “Due to these technical barriers, there are relatively few companies engaged in developing therapeutic drugs for hemophilia. As rAAV gene therapies represent an innovative approach capable of curing genetic diseases, the first rAAV gene drug developed by R&B Bio after its establishment was targeted at hemophilia.”

Hemophilia is a major category of genetic disorders characterized by the inability to form blood clots to stop bleeding after injury. The underlying cause is an impairment in the generation of active thromboplastin, which prolongs clotting time. Patients exhibit a lifelong tendency to bleed following minor trauma, and those with severe disease may experience "spontaneous" bleeding even in the absence of obvious external injury. Based on the specific deficient clotting factor, hemophilia is classified into Hemophilia A (deficiency of clotting factor VIII, accounting for 80–85% of cases) and Hemophilia B (deficiency of clotting factor IX, accounting for 15–20% of cases).

Currently, the primary treatment for hemophilia is “replacement therapy,” which involves administering plasma or clotting factors via injection to raise patients’ plasma factor levels to those sufficient for hemostasis. The clotting factors infused back into the patient can be normal clotting factors derived from healthy donors, or normal clotting factors produced through bioengineering techniques. This approach has, to some extent, contributed to the high cost of hemophilia treatment, which can reach up to $350,000 per person per year.

R&B Bio’s strategy involves using recombinant adeno-associated virus (rAAV) vectors to deliver healthy, highly efficient coagulation factor gene fragments back into the patient’s body. The viral vector does not integrate into the patient’s normal chromosomes; instead, it persists long-term as an independent episomal chromosome. By utilizing raw materials such as amino acids within normal cells, it enables the continuous production of coagulation factors, thereby achieving a curative treatment for hemophilia.

Adeno-associated virus (AAV) is a viral vector commonly used in gene therapy. Due to its advantages, including low immunogenicity, high targeting specificity, and the ability to achieve long-term stable expression of exogenous genes, it is currently one of the most widely used tools in gene therapy. Over 100 AAV serotypes have been identified, and R&B Bio has selected a highly infectious AAV8 produced in human-derived cells.

Furthermore, the coagulation factor adopted by R&B Bio exhibits potency more than five times higher than that of conventional coagulation factors. Dr. Dong Biao stated that this advantage stems from his years of research and development experience in the United States. “During my seven years in the U.S., I devoted most of my time to researching coagulation factors and became highly familiar with the various properties of proteins. For me, it is relatively straightforward to determine how modifying amino acids can enhance the potency of coagulation factors.”

This optimization involves specific alterations at several amino acid positions as well as codon optimization, which constitute R&B Bio’s core competitiveness and technological barriers.Dr. Kim Ji-soo, Investment Director at KIP CapitalHe stated, “As early as 2017, the FDA granted formal approval to Luxturna. Spark Therapeutics’ Luxturna was the first gene therapy drug, but its price tag of $855,000 was prohibitively high, making it difficult for patients to accept. In contrast, Professor Dong’s team has been engaged in research on rAAV gene vectors for many years and has achieved significant milestones in scalable production. They not only innovatively improved the packaging system for rAAV vectors but also developed the VV-Ad/AAV process, which overcame bottlenecks in large-scale manufacturing, resulting in safer and more effective vectors. This revolutionary approach has substantially reduced treatment costs for patients and is expected to significantly improve therapeutic outcomes. I believe R&B Bio has precisely positioned its product, and I am very optimistic about its performance after launch.”

By simultaneously enhancing the infectivity of rAAV and the activity of clotting factors, R&B Bio’s dual-pronged approach enables more efficient rAAV gene therapy at the same dosage, thereby reducing treatment costs. Dr. Dong Biao further stated that the subsequent large-scale production of rAAV gene therapies by R&B Bio could reduce the cost of hemophilia treatment by several fold.

Currently, R&B Bio has established corresponding clinical pipelines for rAAV gene therapies targeting both Hemophilia A and Hemophilia B, having completed preclinical validation in animal models. Among these, the clinical pipeline for Hemophilia B is the company’s current key focus, with plans to complete the Investigational New Drug (IND) application next year; meanwhile, the pipeline for Hemophilia A is expected to have its IND submission completed in the first half of 2022.

However, in addition to its pipeline layout for the genetic disorder hemophilia, R&B Bio is leveraging its technological advantages in recombinant adeno-associated virus (rAAV) gene therapy to establish pipelines in anti-aging and neurodegenerative diseases, including rAAV-based gene drug research targeting Parkinson’s disease and Alzheimer’s disease. AAVs can naturally cross the blood-brain barrier and selectively infect neurons, offering new therapeutic avenues for curing neurodegenerative diseases. Currently, these pipelines are still in the preclinical research stage.

It is reported that R&B Bio has completed an angel round of financing amounting to tens of millions of yuan, led by the Sichuan Talent Fund and KIP Capital, with follow-on investment from Chengdu Tianfu International Bio-town Investment Development Co., Ltd. Currently, the company has also launched a new pre-A round financing plan, with the funds raised primarily intended to advance the clinical trials of its rAAV gene therapy for Hemophilia A and to support talent acquisition.