Purespring Therapeutics presents preclinical data at the 61st ERA Congress
May 24 2024 - 9:57AM
Purespring Therapeutics presents
preclinical data at the 61st ERA
Congress
Data establishes the potential of AAV gene
therapy to deliver transgenes to the podocyte to replace defective
genes or to modulate protein production
Data underpin the potential of AAV as an
important novel modality to treat a broad range of kidney
disease
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.
For further information,
contact:
Purespring:
Julian Hanak, CEOcontact@purespringtx.com+44 (0)20 3855
6324LinkedIn
ICR Consilium
Amber Fennell, Jessica Hodgsonpurespring@consilium-comms.com
Notes to Editors
About Purespring
Purespring is the first and leading company to
treat kidney diseases by targeting the podocyte, a specialised cell
implicated in many renal diseases, through AAV gene therapy
administered directly to the kidney.
Purespring was founded on the work of Professor
Moin Saleem, Professor of Paediatric Renal Medicine at the
University of Bristol, where he heads a world leading
multidisciplinary group researching glomerular diseases. Purespring
seeks to advance gene therapies for the treatment of both monogenic
and non-monogenic chronic renal diseases that are currently poorly
addressed with existing treatments.
For more information please visit:
purespringtx.com and follow us on LinkedIn.