AceLink Therapeutics Files IPO Prospectus to Advance Innovative GCS Inhibitor AL01211 for Polycystic Kidney Disease and Fabry Disease

There are over 6,000 genetic disorders worldwide, the majority of which remain incurable at present. In 2003, the completion of the Human Genome Project marked a milestone that opened new possibilities for identifying numerous genetic diseases that were previously untreatable. By developing diagnostic tools for genetic testing, scientists have been able to guide precision therapies for these “incurable” conditions, thereby paving the way for novel treatment approaches.

Dr. Shen Yuqiao, with over two decades of experience in the pharmaceutical industry, has devoted himself to new drug development. AceLink Therapeutics is the third company he co-founded, focusing on two genetic disorders: polycystic kidney disease and Fabry disease. Previously, Dr. Shen served as a core R&D executive at several prominent U.S. pharmaceutical companies, including Onyx Pharmaceuticals, Applied Biomics, LEAD Therapeutics, and BioMarin.

After graduating from Fudan University, Dr. Yuqiao Shen pursued advanced studies at the University at Buffalo, State University of New York, where he earned a Ph.D. in Molecular Biology. He subsequently completed his postdoctoral training in the laboratory of Dr. Thomas Shenk at Princeton University. “During my postdoctoral work, I had a strong desire to join the pharmaceutical industry. I felt that it was essential to apply the extensive knowledge I had acquired in drug research and development to help others, thereby creating greater value,” stated Dr. Yuqiao Shen.

Dr. Yuqiao Shen, Founder of AceLink Therapeutics

Upon completing his studies, Dr. Shen Yuqiao joined Onyx Pharmaceuticals as his first employer, where he participated in the research and development of anticancer drugs. In Dr. Shen Yuqiao’s own words, he “learned a great deal and built an extensive professional network” during his first job. Later, Onyx Pharmaceuticals was acquired by Amgen, a well-known U.S. pharmaceutical company.

After leaving Onyx Pharmaceuticals, Dr. Shen Yuqiao embarked on his first entrepreneurial venture by co-founding Applied Biomics, a contract research organization (CRO) specializing in biomarker services. Through the study of protein biomarkers, the company guided physicians in delivering precision anticancer therapies to cancer patients. Although Applied Biomics experienced rapid growth, Dr. Shen’s true aspiration remained rooted in his long-standing desire during his academic years: “to enter the pharmaceutical industry.” He was deeply motivated to develop urgently needed new medicines for patients and to engage more profoundly in clinical research and development.

Dr. Shen Yuqiao’s “highlight moment” was his co-founding of LEAD Therapeutics and serving as a senior executive in drug development. There, Dr. Shen spearheaded the early-stage development of small-molecule drugs, achieving significant accomplishments. One of the company’s antibacterial agents was acquired by China’s Chia Tai Tianqing Pharmaceutical Group, while several other candidates—including talazoparib, a PARP inhibitor later approved for marketing in the United States and Europe—were integrated into BioMarin Pharmaceutical’s drug pipeline following its acquisition of LEAD Therapeutics.

Following the company’s acquisition, Dr. Shen Yuqiao served as Executive Director at BioMarin. In addition to overseeing the clinical development of talazoparib (Phase 1 to Phase 3), he led drug discovery programs targeting several rare genetic diseases. Talazoparib, whose development was spearheaded by Dr. Shen at LEAD Therapeutics and BioMarin, received marketing authorization from the U.S. FDA in 2018 and from the European EMA in 2019.

It was this experience at BioMarin that laid the foundation for Dr. Shen Yuqiao’s subsequent establishment of AceLink Therapeutics. “BioMarin is a pharmaceutical company specializing in genetic disorders, where I gained extensive experience. Patients with genetic disorders are geographically dispersed and have historically received insufficient attention, while drug development costs remain prohibitively high. I hope AceLink Therapeutics can contribute to this field by developing innovative therapies for patients with genetic disorders.”

In 2019, Dr. Yuqiao Shen founded AceLink Therapeutics and serves as its CEO. His college classmates, Dr. Li Li and Dr. Jianhong Zheng, co-founded AceLink with him. Leveraging their extensive backgrounds in biotechnology and new drug development, they serve as Vice President of Operations and Vice President of China Region at AceLink, respectively. The company also appointed Dr. Marvin Garovoy as Chief Medical Officer and Dr. Michael Babcock as Senior Director of Research and Development.

Marvin Garovoy, M.D., is a specialist in nephrology and immune-mediated diseases. He previously served as a professor at Harvard Medical School and the UCSF School of Medicine, and after leaving academia, he spent over two decades in clinical drug development within the biopharmaceutical industry. Prior to joining AceLink Therapeutics, Inc., he held senior executive positions, including Chief Medical Officer, at several prominent pharmaceutical companies such as Genentech, XOMA, Hyperion, Arriva, Medgenics, and BioMarin.

Dr. Michael Babcock, Senior Director of R&D at AceLink, has over 15 years of experience in the pharmaceutical industry and has led numerous drug development and exploratory research projects. He previously worked on high-throughput functional genomics and small-molecule screening at Elan Pharmaceuticals, and later joined Dr. Yuqiao Shen’s team at BioMarin, where he spearheaded several small-molecule drug development programs targeting rare diseases.

Why polycystic kidney disease and Fabry disease? Because both conditions represent significant unmet clinical needs.

Polycystic Kidney Disease (PKD) is a genetic disorder characterized primarily by the development of numerous cysts in both kidneys, leading to progressive renal enlargement and eventual complete loss of kidney function. Symptoms typically manifest between the ages of 30 and 40, with accelerated disease progression around age 50; approximately 50% of patients progress to end-stage renal disease by age 60. According to estimates from the National Institutes of Health (NIH) and other research institutions, the prevalence of PKD is approximately 1 in 500 to 1 in 1,000, making it a relatively common "rare disease."

Treatment options for patients with this disease are very limited, often resorting to hemodialysis or kidney transplantation only when renal failure occurs. Currently, only one drug is approved worldwide for the treatment of autosomal dominant polycystic kidney disease (ADPKD)—Otsuka Pharmaceutical's small-molecule drug tolvaptan. However, its efficacy is less than ideal, and it carries risks of hepatotoxicity and numerous side effects, which significantly limit its clinical application.

From 2014 to 2018, tolvaptan was successively approved in Japan, Europe, and the United States for the treatment of polycystic kidney disease. Despite concerns such as hepatotoxicity, its global sales in the ADPKD market reached $800 million in 2019, with projected sales of $1 billion in 2020, reflecting the substantial market potential for ADPKD therapies.

Dr. Yuqiao Shen and Dr. Michael Babcock oversaw the small-molecule glucosylceramide synthase (GCS) inhibitor program while at BioMarin. Following the establishment of the independent company AceLink, the company has obtained a patent license for the GCS inhibitor program from BioMarin, securing exclusive (sublicensable) rights and global patent protection worldwide.

GCS inhibitors have demonstrated safety in humans across multiple clinical trials, and a small-molecule GCS inhibitor has already been approved for the treatment of type 1 Gaucher disease. Leveraging the successful clinical development experience of existing GCS inhibitors, AceLink Therapeutics is developing small-molecule GCS inhibitors targeting polycystic kidney disease (PKD). In multiple mouse models of PKD, GCS inhibitors have shown significant therapeutic effects, including reductions in kidney size and cyst volume, as well as preservation of renal function.

Regarding the underlying therapeutic mechanism, Dr. Shen Yuqiao explained, “GCS inhibitors can suppress the synthesis of various glycolipids, thereby reducing renal epithelial cell proliferation and alleviating kidney inflammation. Excessive glycolipid synthesis is the root cause that stimulates renal epithelial cell growth and triggers kidney inflammation, which further exacerbates the progression of polycystic kidney disease.”

Currently, AceLink has selected a non-blood-brain barrier-penetrating GCS inhibitor (pipeline candidate AL01211) for the treatment of polycystic kidney disease. Patients require only once-daily oral administration to slow and reverse the decline in renal function. AceLink anticipates initiating clinical trials for AL01211 around the end of 2020.

In addition to polycystic kidney disease, GCS inhibitors can be used to treat Fabry disease. All Phase I clinical and preclinical data from the company’s AL01211 pipeline can be shared across both indications, further increasing the likelihood of success for the AL01211 project.

Fabry disease is an X-linked lysosomal storage disorder (Gb3 accumulation) caused by mutations in the GLA gene, leading to systemic organ involvement.

Currently, the standard treatment for Fabry disease is enzyme replacement therapy (ERT). Although ERT is effective in controlling the progression of Fabry disease, its therapeutic efficacy is limited in certain organs due to the poor tissue penetration of large-molecule enzymes; for instance, it has limited effectiveness in treating renal lesions. Furthermore, ERT is prohibitively expensive, with annual treatment costs reaching up to $300,000 per patient, and requires intravenous administration, which is highly inconvenient.

Small-molecule GCS inhibitors may offer new oral therapies for this condition that are more effective, convenient, and cost-effective. Globotriaosylceramide (Gb3), which causes Fabry disease, is a glycolipid whose synthesis depends on the activity of the enzyme glucosylceramide synthase (GCS). GCS inhibitors can directly suppress Gb3 synthesis, thereby reducing its accumulation in patients’ cells.

In 2017, the global market for Fabry disease treatments was valued at $1.57 billion, with enzyme replacement therapy accounting for over 85% of the market share. AceLink’s small-molecule GCS inhibitor, currently in clinical development for Fabry disease, aims to provide new therapeutic opportunities for patients and address unmet clinical needs.

Currently, AceLink Therapeutics completed a seed funding round worth tens of millions of RMB in July 2019, with joint investment from Viva Biotech, Cathay Capital, Shengshan Capital, and Hua’an Bio. The company has recently initiated a new pre-A financing round to advance the Phase I clinical trial of AL01211 and to introduce new R&D projects for genetic disease drugs.