Purespring Therapeutics presents preclinical data at the 61st ERA Congress

London— 24 May 2024

Purespring Therapeutics, a pioneering gene therapy company focused on transforming the treatment of kidney diseases, is presenting preclinical data at the 61st European Renal Association (ERA) Congress, showing that transgenes can be efficiently targeted to podocytes to replace defective genes or to use the podocyte as a protein factory to modulate kidney biology.

The presentation: “A novel podocyte gene therapy enables pathway to clinical translation for the treatment of glomerular diseases” is being presented today at the ERA Congress, taking place in Stockholm, Sweden from 23-26 May.

Adeno associated vector (AAV) gene therapy has the potential to treat a wide range of kidney disease via the targeted delivery of genes to kidney cells, but historically, kidney AAV gene therapy has been challenging due to technical and physiological hurdles limiting effective delivery.

The presentation, by Sam Illingworth, Purespring’s Head of Translational Research, demonstrates the development of Purespring’s novel AAV gene therapy which can efficiently deliver transgenes to podocytes, a specialised kidney cell implicated in the majority of glomerular kidney disease. Exemplified through the development of PS-001, both murine model and large animal data show this approach can effectively target transgenes to podocytes to replace defective genes and rescue kidney function, providing an important novel modality for treating a broad range of kidney diseases.

Alice Brown, Purespring’s Chief Scientific Officer, commented:

“These data show that an AAV gene therapy can be used to deliver transgenes effectively, specifically, and safely to podocytes and establish this approach as a modality to treat many glomerular diseases. This sets us on a clear pathway towards clinical development for PS-001 and other kidney indications in our pipeline, and we’re excited to be able to present this to the international nephrology community.”

Julian Hanak, Purespring’s Chief Executive Officer, added:

“This highlights the potential of our podocyte-targeting approach to stop, reverse and potentially cure chronic kidney diseases. Affecting over 840 million people worldwide, chronic kidney disease places an innumerable burden both on patients and their families, as well as on global health systems.”

Methods to translate Purespring’s approach to a clinical setting were also established, with additional toxicological assessments of renal and other organ function showing no pre-clinical treatment-related safety concerns.

PS-001 is being developed as a novel approach to treat steroid resistant nephrotic syndrome caused by mutated NPHS2 and may become the first podocyte targeted gene therapy to enter clinical development.

Results

Using our AAV gene therapy platform, which includes a capsid that is highly effective at transducing human podocytes and promoter that drives gene expression specifically in the podocyte, the gene therapy product PS-001 encoding NPHS2 has been generated.

Using a murine analogue of PS-001, in vivo proof of concept studies in a translationally relevant murine disease model (Nphs2R140Q/-) showed NPHS2 delivery and podocin expression in glomeruli and efficacy in terms of renal function rescue. This was demonstrated by resolution of severe proteinuria improved serum albumin and reduction in glomerulosclerosis.

The methods to translate the approach to the clinical setting were established in pigs. Administration of PS-001 resulted in transgene mRNA expression across 89% ± 11% of kidney glomeruli as assessed by RNAScope, and transgene derived podocin protein could be specifically detected in podocytes. Using qPCR, RT-PCR and ELISA it was shown that using local administration, podocin gene expression was restricted exclusively to the kidney glomerulus, with gene expression undetectable in off-target organs including the liver. Additional toxicological assessments of renal and other organ function from urine and blood, and post-study histopathological assessments revealed no pre-clinical treatment-related safety concerns.