Saimoruo Pharma: 18 Years of Dedicated Research Paves Way for Breakthrough in Novel Neuropathic Pain Therapeutics

For Dr. Li Shuai, entrepreneurship was not his first choice. In the two years prior to leaving the Chinese Academy of Sciences, Dr. Li had been attempting to integrate the efforts of research institutions, hospitals, pharmaceutical manufacturers, and local governments to jointly facilitate the translation of basic scientific achievements into market-driven products. Despite significant investments of time and energy, progress was hindered by systemic barriers and the state of China’s R&D ecosystem. To this day, the domestic ecosystem for original drug development remains in its infancy; academic institutions still prioritize publication output, while the industry focuses largely on the rapid imitation of international products. How can an innovative ecosystem be established within China’s pharmaceutical industry to organically integrate basic scientific research with biopharmaceutical R&D? Dr. Li believes that the first step is to achieve a qualitative leap from 0 to 1 by setting an industry benchmark. This was the original intention behind founding Shanghai Sai Murrow Biotechnology Co., Ltd., and the basic scientific achievements from Dr. Li’s work in Academician Zhang Xu’s laboratory undoubtedly provided the ideal catalyst.

Compared to the stable career at the Chinese Academy of Sciences, entrepreneurship is an uncertain, risky, and protracted journey. Dr. Li Shuai’s confidence stems from the value of the project: Academician Zhang Xu has accumulated 35 years of expertise in this field, while Dr. Li has dedicated 12 years to foundational theoretical research on this topic. Ample foundational theory and clinical translation data support our project’s advantage in replacing existing first-line clinical medications and opioid drugs, thereby meeting clinical needs.

Shanghai Sai Murrow Biotechnology Co. Ltd. has entered its sixth year of operations, having initiated clinical trials for its investigational new drug SR419 in patients with peripheral neuropathic pain and administered the first dose to a patient. Additionally, five other pipeline products are advancing toward clinical development in an orderly manner. The company plans to bring two products into clinical trials annually over the next three years and complete Phase II clinical studies for two products. According to Dr. Li Shuai, Shanghai Sai Murrow’s product portfolio is successively entering a period of rapid growth. His professional focus has shifted from translational research to commercialization, marking both a new challenge and a phase of significant achievement for him.

Neurological disorders can be categorized into two major classes: those caused by abnormal neuronal excitability, such as chronic pain, epilepsy, and depression; and those caused by neuronal death, such as Alzheimer’s disease, Parkinson’s disease, and diabetic retinopathy. Among these, chronic pain has the highest prevalence and imposes the greatest socioeconomic burden. In the United States alone, it results in $680 billion in indirect economic losses, and nearly 50,000 people die annually from opioid misuse. To combat the opioid crisis, the U.S. government declared a “public health emergency” in 2018. Pharmaceutical companies such as Johnson & Johnson and Purdue Pharma were fined more than $10 billion, leading Purdue and several other companies to file for bankruptcy. The global opioid market is currently valued at approximately $25 billion. In recent years, numerous international companies have actively invested in the research and development of non-opioid analgesics aimed at replacing opioids.

According to Dr. Li Shuai, ion channels in neuronal cells are responsible for transmitting electrical signals and often determine neuronal excitability. The underlying cause of pain perceived by the human brain is the reception of electrical signals by brain neurons. Sai Murrow Biotechnology has developed an original new drug based on ion channel mechanisms, which holds the potential to replace opioids. “Through systematic comparisons with commonly used international analgesics and drugs under development, our drug demonstrates advantages in both safety and efficacy. Notably, SR419 shows significant advantages in safety.” Dr. Li also revealed that patient efficacy data are being gradually collected, with partial clinical results expected to be presented at international academic conferences in 2021.

Furthermore, since 2018, Shanghai Sai Murrow Biotechnology Co. Ltd. has expanded its product portfolio to include neuroinflammation therapies. Necrosis of human tissue triggers an inflammatory response; similarly, the death of neurons in the brains of patients with Alzheimer’s disease and other conditions also induces inflammation. By intervening in this inflammatory response, it is possible to protect brain neurons. Prior to launching its neuroinflammation product line, the company’s team conducted in-depth research and discussions for a full year. They concluded that this mechanism holds significant development potential and aligns well with the team’s technical capabilities. Related products are expected to enter clinical trials in the third quarter of next year.Dr. Li Shuai pointed out that recent international M&A transaction prices in the field of neuroinflammation have become excessively high. Investigational projects merely in Phase I clinical trials can often command valuations exceeding $1 billion, with upfront payments no less than several hundred million dollars. “Nevertheless, we must provide more evidence and compare our target with similar international targets to demonstrate that our target is superior to others and that our product quality exceeds industry standards. At the same time, we must maintain a clear-headed understanding of this field. Emerging areas will inevitably encounter various challenges and setbacks. Particularly given that the pathogenesis of Alzheimer’s disease is multifactorial, we will seek collaboration with international professional companies to jointly develop drugs for related diseases after establishing a robust chain of translational evidence.”

Currently, the common challenge facing the two major mechanisms of ion channels and neuroinflammation lies in translational research. Typically, translational research requires comprehensive studies spanning cellular levels, animal tissue levels, and animal behavior and function, supported by pathological data from patient tissues and relevant clinical patient data. Only when all data align perfectly to form a complete theoretical framework can a drug advance into clinical trials. Although such research is highly time-consuming, successful products often bring revolutionary changes to the respective disease fields.

Shanghai Sai Murrow Biotechnology Co. Ltd. designs clinical trials based on its independently developed scientific theoretical models, thereby optimizing and refining its R&D strategy: it selects specific, small patient cohorts for rapid, low-cost, quantitative proof-of-concept studies in clinical settings. Dr. Li Shuai pointed out that this is the key distinction between Sai Murrow and major international pharmaceutical companies. Global big pharma often places insufficient emphasis on the integrity of preclinical research data and translational data, instead prioritizing direct testing in clinical patients. This trial-and-error approach has resulted in exceptionally high clinical failure rates.

Innovation in the pharmaceutical industry is often grounded in advances in scientific theory and technology, with both models jointly driving progress in the biopharmaceutical sector. The CRISPR technology, which garnered the Nobel Prize this year, is a typical example of technological innovation, and many companies both internationally and in China are engaged in related research. In contrast, PD-1 monoclonal antibody drugs represent a case of new drug development based on innovations in scientific theory. In 1992, Dr. Tasuku Honjo’s laboratory discovered PD-1, the first factor identified as inducing programmed cell death in immune cells. It was not until 2014 that Opdivo received approval for marketing in Japan, a journey spanning 22 years of continuous research and collaborative efforts among multiple institutions, including Kyoto University, Ono Pharmaceutical, Medarex, and Bristol-Myers Squibb. From the serendipitous discovery of a biological phenomenon to the refinement of relevant theoretical frameworks, the establishment of comprehensive scientific and translational theories, and ultimately the development of a marketed drug, a 20–25-year cycle is the norm for original drug development, posing significant challenges for both investors and entrepreneurs. However, according to Dr. Li Shuai, at least in the field of neurological drug development, the prolonged timelines for theoretical research and translation have actually enabled the emergence of a number of startups. This is because the time costs for small companies to conduct translational research are substantially lower than those for multinational pharmaceutical corporations, presenting an opportunity for emerging biotechnology firms to challenge industry giants.

In the spring of 2002, Li Shuai entered Academician Zhang Xu’s laboratory and took on the screening of drug targets using gene chips as his first graduate research project. By the autumn of 2020, when the first patient with peripheral neuropathic pain received treatment, Dr. Li had finally led his team to largely complete both the theoretical and translational research on a novel drug mechanism. Each step forward represented an effort to find answers to unknown questions. At this moment, he is firmly convinced that the technology he has dedicated nearly two decades to studying will ignite enthusiasm within the industry. For Dr. Li, the new unknown challenge lies in restructuring the team, which has operated like an R&D center for over six years, to equip it with sufficient commercialization capabilities and establish international influence in the future. He told VCBeat that this is currently the most challenging issue, but it must be resolved within the next year.

Writing Reference:

Chen Kaixian: From Imitative Innovation to Original Innovation, How Can China’s Pharmaceutical Industry Take a Critical Step?