TsingStars Biopharma Targets 55 Anti-Aging Gene-Related Targets and Advances 11 Proprietary Pipelines Within Four Years

“The Capital Winter” was a frequently discussed topic in the biopharmaceutical sector in 2022.

The biopharmaceutical industry encountered numerous challenges this year. As China’s capital market cooled and investors adopted a more cautious approach, biopharmaceutical companies faced increasing difficulties in securing financing. Furthermore, amid the “capital winter,” the market capitalization of listed biopharmaceutical companies continued to shrink, significantly compressing their commercial space. In response, enterprises have resorted to measures such as layoffs, R&D pipeline adjustments, and cost reductions to ensure survival.

However, with the end of the pandemic and the economic recovery, the biopharmaceutical industry has also ushered in many opportunities. Domestic innovative pharmaceutical companies are gradually initiating the processes of "going global" and import substitution. According to a report by Stifel, in the first half of 2023, China became a net exporter of pharmaceutical innovations for the first time, with 12 asset out-licensing deals compared to 8 in-licensing deals.

According to incomplete statistics from VCBeat’s Orange Fruit Bureau, the number of financing and investment deals in China in H1 2023 decreased by five compared with the same period last year, remaining largely flat; the total financing and investment amount was approximately RMB 37.557 billion, a 30% decline year-on-year. Globally, however, the number of financing and investment deals in H1 2023 rose by 29% year-on-year, and the total global financing amount increased by 9% year-on-year. The global capital market was more active this year than last, with an increase in both deal frequency and total financing volume, sending some positive signals to the biopharmaceutical industry and indicating a warming trend in capital markets.

In this context, Shuimu Xingchen Biopharmaceutical (Shenzhen) Co., Ltd. (hereinafter referred to as “Shuimu Xingchen”) seized the opportunity presented by the market recovery and signed an agreement with the Shenzhen International Graduate School of Tsinghua University to jointly promote the commercialization of long non-coding RNA (LncRNA) projects, completing its first round of financing in March 2023. In the field of nucleic acid therapeutics, the company did not pursue the popular mRNA track; instead, considering both clinical and market dimensions, it adopted a differentiated strategy by focusing on the LncRNA track. In July of the same year, it integrated a nanobody pipeline into its portfolio, actively advancing the research, development, and commercialization of antibody-oligonucleotide conjugate (AOC) drugs.

In addition, leveraging its technological and team advantages, Shuimu Xingchen has built and integrated three major technology platforms—RNA therapeutics, nanobodies, and CGT therapies—to strategically position itself in the core competitive areas of future biopharmaceuticals.

Since its establishment, Shuimu Xingchen has successfully launched 11 self-developed product pipelines, with indications covering oncology, anti-infection, tissue repair and anti-aging, neurodegenerative diseases, and other fields. Among them,One tissue repair product is about to enter clinical trials, while three anti-aging products are poised for marketing approval and are expected to go on sale by the end of December.。

Professor Zhang Ya’ou, Chief Scientist of Nucleic Acid Drugs at Shuimu Xingchen, holds an M.D. from West China University of Medical Sciences. He previously served as an Associate Professor and Deputy Chief Physician in Pediatric Hematology-Oncology at West China University of Medical Sciences. He later conducted postdoctoral research in Molecular and Cell Biology at the University of Toronto and simultaneously served as a Postdoctoral Fellow in Molecular and Cell Biology at Harvard University. In 2004, he was appointed as Professor and Doctoral Supervisor at the Shenzhen Graduate School of Tsinghua University. He currently serves as Director of the Shenzhen Key Laboratory of Health Science and Technology.

Professor Zhang Ya’ou has long been engaged in research on non-coding nucleic acids and small nucleic acid therapeutics, serving as the principal investigator of the small nucleic acid drug research group under the National Major Special Project for New Drug Innovation during the 11th and 12th Five-Year Plan periods. With a clinical background, Professor Zhang has been committed to promoting the market translation of scientific research projects, aiming to enable more patients to benefit from his research and provide more affordable and effective therapeutic options for those who currently have limited access to treatments.

Founder Zhao Xuxiang has nearly a decade of experience in the biopharmaceutical industry and is a seasoned entrepreneur. During his tenure at overseas pharmaceutical companies, Zhao witnessed the approval and market launch of multiple cell and gene therapy (CGT) drugs. Although China approved the world’s first CGT drug, Gendicine, in 2003, the number of CGT drugs currently approved for marketing in China remains limited. Zhao stated, “In the field of biomedicine, although China started early, there are still shortcomings in technology and targets, with significant homogenization issues. Moreover, there remain unmet clinical needs in areas such as CGT.”

Therefore, Zhao Xuxiang decided to build a team and establish a company, adopting a differentiated strategy in the cell and gene therapy (CGT) sector. Subsequently, based on an analysis of hotspots in the biopharmaceutical field and market demands, the company expanded its coverage to include small nucleic acid drugs and nanobody therapeutics. To date, Shuimu Xingchen has successfully established 11 proprietary pipelines over four years, with indications spanning multiple therapeutic areas.

Behind the rapid growth of Shuimu Xingchen lies a team with professional backgrounds and extensive experience. Notably, 90% of the R&D team members hold doctoral degrees, while the majority of the management team comes from Fortune 500 companies.

Furthermore, over 72% of the human genome is transcribed into long non-coding RNAs (lncRNAs), which far outnumber proteins, indicating a greater potential for drug targets. However, lncRNAs have a limitation: unlike traditional mRNA knockout methods, lncRNAs cannot be knocked out via frameshift mutations.

Leveraging its technical team, Shuimu Xingchen has successfully addressed the challenge of LncRNA knockout. Professor Zhang Ya’ou and her team discovered that a CRISPR-Cas9-based LncRNA knockout strategy (BESST) can efficiently and specifically induce nuclear degradation of target LncRNAs, thereby ablating their function.

Meanwhile, the company has established an RNA technology platform based on an AI-driven big data drug screening model. This platform enables rapid screening of RNA databases and quick prediction of the druggability of candidate targets, ultimately shortening the drug selection process.

Building on this foundation, Professor Zhang Ya’ou and her R&D team identified a unique target. Studies have shown that upregulating this target enhances the expression of nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) in the hippocampus and exerts positive regulatory effects on 55 anti-aging genes.

This means that intervening at this target can directly increase the expression products of anti-aging genes, enhance their expression, and truly reverse aging at the epigenetic level. In skin cells, targeting this site can increase the expression of facial anti-aging components such as collagen, elastin fibers, and hyaluronan synthase by more than threefold. Further evidence confirms that this target also plays a role in neurodegenerative diseases and other conditions.

On January 12, 2023, Professor David Sinclair of Harvard Medical School (Co-Director of the Paul F. Glenn Center for Biology of Aging Research) published a study in Cell titled “Loss of epigenetic information as a cause of mammalian aging.” He posits that epigenetic alterations are the primary driver of mammalian aging and that restoring epigenomic integrity can reverse signs of aging. Professor David Sinclair has gained worldwide recognition for his research on NMN (nicotinamide mononucleotide, a precursor of NAD+) and was named one of Time magazine’s 100 Most Influential People in 2014.

On March 28, 2023, Professor João Pedro de Magalhães of the University of Birmingham, UK, published a review article titled “Ageing as a software design flaw” in the journal Genome Biology. He argues that aging is not caused by the inevitable deterioration of the body’s hardware, such as chronic inflammation or oxidative damage to cells from free radicals, but rather by inherent design flaws in its software—specifically, epigenetic changes that activate or silence gene expression programs. These epigenetic alterations, in turn, lead to changes in cellular function and phenotype, a perspective that aligns with the research of Professor David Sinclair.

On December 8, 2023, researchers from the University of Copenhagen in Denmark published their latest findings in the journal Science. The study revealed that increased reactive oxygen species (ROS) associated with obesity and aging can activate the ribotoxic stress response (RSR) mediated by ZAKα, a member of the MAP3K family. This activation leads to ribosome stalling and collisions, impairing protein translation and resulting in metabolic dysregulation. These findings provide direct evidence supporting Professor João Pedro de Magalhães’s view that reactive oxygen species directly damage the integrity of the epigenome, thereby driving aging.

The discovery and research of the aforementioned targets by Professor Zhang Ya’ou’s team will usher in a new chapter in anti-aging research, while also providing novel solutions to address the challenges of aging.

To date, 15 oligonucleotide drugs have been approved for marketing worldwide. Among them, Nusinersen (Spinraza), which was launched in 2016, achieved sales of $1.7 billion in 2022. According to incomplete statistics, Nusinersen is currently the best-selling antisense oligonucleotide (ASO) drug.

The commercial success of small nucleic acid drugs has made them a focal point for the industry and investors, attracting numerous companies to enter the field. According to a report by Research And Markets, the global market size for small nucleic acid drugs reached $6.1 billion in 2022 and is projected to grow to $19.9 billion by 2030, with a compound annual growth rate (CAGR) of 15.9%. In the future, the therapeutic applications of small nucleic acid drugs are expected to expand continuously, positioning them to become the third major class of drugs following small-molecule drugs and antibody-based therapies.

As a participant in this hotly contested sector, Shuimu Xingchen has completed a pre-A financing round worth tens of millions of yuan and, leveraging its team’s strengths, has established its technology platform and laid out its product portfolio.

Currently, Shuimu Xingchen is in a new round of financing to further advance its pipeline into clinical trials. In the future, the company will accelerate the progression of its pipeline into clinical trials to rapidly achieve a closed commercial loop. Meanwhile, the company will further expand into overseas markets and promote the global launch of its products and technologies.

Despite the advantages of oligonucleotide drugs, such as simple design, short R&D cycles, strong target specificity, and long-lasting efficacy, challenges remain in their development, including a shortage of R&D talent and a lack of industrialization technologies. In response, Shuimu Xingchen will leverage regional industrial and talent advantages to comprehensively plan and expand its production capacity layout. Meanwhile, the company will increase R&D investment to continue promoting the integrated innovation of RNA, nanobody, and CGT technologies, ensuring smooth progress in R&D and ultimately achieving successful commercial translation of its products.

"In the face of a fiercely competitive market for innovative drugs, Zhao Xuxiang stated, 'Shuimu Xingchen Biopharmaceutical will continue to explore and accelerate its pace to bring more high-value innovative drug products to clinical practice, serving as a genuine practitioner in the biopharmaceutical industry.'"

References:

1. Chi Y,Wang D,Wang J,et al.Long non-coding RNA in the pathogenesis of cancers[J].Cells,2019,8(9):1015.