LONDON, UK — October 27, 2026
Purespring Therapeutics, a precision nephrology company developing genetically targeted therapies for kidney diseases, announced new preclinical findings supporting the advancement of PS-003, an investigational gene therapy candidate for X-linked Alport Syndrome (XLAS). The findings were presented at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado, alongside a global genetic analysis examining more than 1.2 million genomes. PS-003 is designed to address the underlying genetic cause of XLAS by delivering a functional copy of the COL4A5 gene to podocytes, specialised kidney cells responsible for producing key components of the glomerular basement membrane. In studies involving human podocytes, PS-003 enabled production of full-length COL4A5 and supported the formation of functional collagen protein complexes. Additional studies in an XLAS mouse model and Göttingen minipigs demonstrated kidney-targeted gene delivery and supported further development. Purespring plans to submit an Investigational New Drug (IND) application in 2027, with the aim of progressing PS-003 towards first-in-human studies.
Preclinical Results Demonstrate Functional COL4A5 Production
The presentation, titled “GlomThera™ platform enables durable COL4A5 expression for the treatment of X-Linked Alport Syndrome,” described PS-003’s ability to produce and secrete full-length COL4A5 in human podocytes without detectable unwanted by-products. The protein formed functional COL4A3/4/5 collagen heterotrimers in a dose-dependent manner, supporting the potential to restore an essential component of the kidney’s filtration structure. COL4A5 was also detected in the glomerular basement membrane-like matrix of a three-dimensional glomerulus model, providing additional evidence of biological activity in a system designed to represent relevant kidney structures. In an XLAS mouse model, a single intravenous dose of a murine surrogate vector produced sustained COL4A5 expression localised to the glomerular basement membrane. The treatment also restored COL4A3 and COL4A4 protein signals that were largely undetectable in untreated animals. Together, these findings support further investigation of PS-003 as a potential approach to addressing the molecular defect underlying XLAS.
Minipig Studies Support Kidney Delivery and Further Safety Evaluation
Additional studies in Göttingen minipigs, a translational model used in kidney research, demonstrated that a surrogate PS-003 vector delivered the full-length COL4A5 gene to the kidney, with messenger RNA detected in most glomeruli. Purespring reported no treatment-related safety concerns in these studies, including at doses substantially above the highest dose planned for clinical development. The findings provide encouraging evidence on kidney delivery and preliminary safety in an animal model, although they do not establish safety or efficacy in humans. PS-003 is built on the company’s proprietary GlomThera™ platform, which is designed to target podocytes and enable local delivery of genetic therapies. The platform also underpins PS-002, Purespring’s kidney-targeted gene therapy candidate for IgA nephropathy, which has already been administered to patients and is in clinical development. The company believes the PS-003 approach may have potential beyond XLAS, including certain forms of Alport Syndrome associated with variants in COL4A3 and COL4A4, subject to further research and development.
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Global Genetic Study Highlights Alport Syndrome Burden and Unmet Need
A second presentation examined the global mutational landscape of COL4A3, COL4A4 and COL4A5 using data from more than 1.2 million genomes across the United States, United Kingdom, Europe and Japan. The analysis was assessed against real-world clinical data from Natera’s Renasight™ database and the European Rare Kidney Disease Reference Network. Using a conservative method focused on known disease-causing variants and variants predicted to switch off gene function, researchers estimated that approximately 150,000 people in the United States have moderate or severe XLAS. The analysis also estimated that 3.2 million people in the US, or approximately one in 107, carry a disease-causing variant in one of the two Alport-associated genes on chromosome 2. More than 1,800 distinct pathogenic variants across the three genes were identified, highlighting substantial genetic diversity and differences in the most common variants between geographical populations. The findings also suggested that later-onset variants and intronic variants may contribute to underdiagnosis, reinforcing the importance of genetic testing for patients with suspected inherited kidney disease. Purespring said the combined preclinical and epidemiological findings strengthen the rationale for advancing PS-003 towards clinical development, with an IND submission planned for 2027.
Source:Purespring Therapeutics Press release
