ADPKD

Autosomal Dominant Polycystic Kidney Disease
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DISEASE OVERVIEW

ADPKD is a severe disease that causes cysts to form in a patient’s kidneys, which can ultimately lead to kidney failure, dialysis and transplantation.

ADPKD is caused by insufficient expression of the PKD1 gene in the renal tubular epithelial cells of the kidney. There are no available therapies for patients with ADPKD that address the underlying cause of the disease.

PYC has developed PYC-003, a treatment that could arrest the disease course of ADPKD and enable regeneration and restoration of kidney function. PYC is currently conducting investigational new drug (IND) enabling studies in PYC-003.

ADPKD at a glance

An overview of key disease information.
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An urgent need to create treatments

ADPKD affects 1 in every 1,000 people.1

An icon of two strands of RNA next to each other. The strand on the left is navy blue and the strand on the right is orange. Both strand are otherwise identical. They are both gently curved vertical lines with short horizontal lines staggered downwards like the rungs of a ladder.

ADPKD is a monogenic disease

Approximately 80% of ADPKD patients have a mutation in one of their two copies of the PKD1 gene.2

An icon of a set of navy blue kidneys connected by a large blood vessel with orange cysts all over them.

Development of fluid-filled cysts

Patients with ADPKD develop fluid-filled cysts in their kidneys that destroy kidney function, with more than 50% of patients reaching end-stage renal failure in their 50s.3 The cysts cause patient’s kidneys to expand up to the size of a football, significantly larger than a normal fist-sized kidney.

An icon of two navy blue kidneys connected by a large blood vessel. There are two curved orange arrows around the kidneys that create the appearance of a circle.

PYC's therapy, PYC-003, seeks to restore function

ADPKD patients have a mutation in one copy of the PKD1 gene – this leads to their kidney cells producing half as much PC1 protein as is required for normal function. PYC-003 increases PKD1 gene expression, which could arrest disease progression, enable damaged kidneys to regenerate, and restore function.

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Encouraging results

PYC-003 is currently in IND enabling studies.

ADPKD at the genetic level

Understand how a single genetic mutation causes lifelong disease.
An icon of four DNA spirals organised into two sets of pairs. The DNA pairs on the left are both blue and white, and are titled 'Unaffected DNA'. One DNA pair on the right is orange and white while the other is blue and white. This set of DNA is titled 'ADPKD patient DNA'.

Genetic mutation

ADPKD patients have a mutation in one of their two copies of the PKD1 gene – this mutation is present in all the cells in their body but it causes disease in the retinal tubular cells of the kidney.

An icon of two sets of RNA pairs side-by-side. The set on the left is blue and is titled 'Unaffected person'. There is a white arrow below this pair pointing down towards two strands of PC1 protein chains. On the right, one strand is orange and one is blue within the pair. It is titled 'ADPKD patient'. There is a white arrow below this pair pointing down towards one strand of PC1 protein chain and a white bubble containing the text '-50%'.

Decreased protein production

The PKD1 gene mutation creates an unstable RNA message – this leads to approximately half as much PC1 protein production as is required to function normally. PYC’s therapeutic, PYC-003, seeks to increase protein expression in the remaining healthy copy of the PKD1 gene to restore PC1 protein production to levels that are sufficient for the cells to function normally.

An icon of a set of kidneys connected by a large blood vessel with orange cysts all over them. Beneath the icon, the title 'kidney phenotype' is printed.

Cellular changes

Underproduction of the PC1 protein causes increased epithelial cell proliferation and fluid secretion, which leads to cyst formation in the kidneys.

 

PYC-003 has disease-modifying potential to halt cellular changes and arrest disease progression – it’s a potentially life-changing therapeutic.

An icon of a set of enlarged and deformed kidneys connected by a large blood vessel with orange cysts all over them. Beneath the icon, the title 'enlarged kidneys' is printed.

Patient symptoms

Over time, insufficient PC1 protein production causes these cysts to increase in size and count, which leads the kidneys to enlarge (up to the size of a football) and decline in function – this results in renal failure for most patients, with the patient ultimately requiring regular dialysis and organ transplant

 

At PYC, we aim to eradicate the development of ADPKD symptoms with our first-in-class drug candidate, PYC-003.

The human impact of ADPKD

ADPKD is a severe, progressive disease characterised by the development of fluid-filled cysts in the kidney, which often results in kidney failure.
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10 years old

Patients start to develop kidney cysts in childhood, although symptoms don’t typically occur until adulthood.

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40 years old

At first, patients can experience symptoms or signs including high blood pressure, blood in the urine, abdominal and side swelling or pain, urinary tract infections and kidney stones.

An image of a smiling elderly man seated on a chair. There is a clinician wearing blue scrubs and a stethoscope who is standing behind him. The clinician has their right hand placed on the man's shoulder and the man has his hand placed over the top.

60 years old

Approximately 50% of patients develop end-stage kidney failure that requires dialysis or a kidney transplant to treat.

PYC-003 is a potentially life-changing treatment

PYC-003 is a transformative RNA therapeutic that addresses the underlying PKD1 gene mutation to effectively treat disease at its root cause. By treating ADPKD at the genetic level, PYC-003 has the potential to halt disease progression and allow ADPKD-affected kidneys to restore function.

A table that contains three columns titled 'Unaffected individual', 'ADPKD patient' and 'ADPKD patient + PYC-003' from left to right. In the 'Unaffected individual' column there is light and dark blue DNA, two strands of dark blue RNA and two strands of PC1 protein, these are labelled '100%'. In the 'ADPKD patient' column there is dark blue and orange DNA, one strand of dark blue and one strand of orange RNA and one strand of PC1 protein, labelled '~50%'. In the 'ADPKD patient + PYC-003' column there is dark blue and orange DNA, one strand of dark blue and one strand of orange RNA and two strands of PC1 protein, these are labelled 'up to 100%'.

In pre-clinical testing, high concentrations of PYC-003 reached target kidney cells affected by ADPKD, and PYC-003 increased PC1 protein production by approximately 50% three days after a single dose.

Cells from ADPKD patient kidneys were grown and treated with PYC-003 in-vitro. Visible reductions in cyst size and frequency were observed in PYC-003-treated patient cells compared to untreated cells – demonstrating the potential efficacy of PYC-003 for ADPKD patients.

A bar graph with two images to the right of it. The y-axis of the bar graph is titled 'Cyst area (um2 fold change)'. There are two clusters of dots on the bar graph. The cluster to the left is titled 'Untreated' and achieves an average value of approximately 1.0. The cluster to the right is titled 'PYC-003 (20um)' and achieves an average value of 0.4. To the right of this bar graph there is a scientific photo of large purple, pink and red cysts. This photo is titled 'Untreated 3D cyst model'. There is an arrow pointing away from this photo to a second photo titled 'PYC-003 treated 3D cyst model'. This photo has much smaller purple, pink and red cysts in it.
Reduction in cyst size and frequency following treatment with PYC's drug candidate (PYC-003) in a human 3D model generated using tissue collected directly from the kidneys of ADPKD patients. The assay shows larger cysts (stained with blue and red) in the untreated 3D model when compared to the PYC-003-treated 3D model. Untreated control samples treated with 5% H2O. *representing a p value of <0.0001 using student's t-test.

Patients are our priority

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Our commitment to patients

We believe it is essential to understand the people living with the genetic diseases that we are aiming to treat. At PYC, we make it a priority to collaborate with patients and caregivers across our development process – to ensure that our RNA therapeutics best meet their needs.

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Our patient trials

At PYC, we conduct responsible patient trials to ensure that our treatments are safe and effective. These trials rely on patient volunteers and are crucial to the development of disease-modifying therapies for genetic diseases.

References

  1. Willey C, Kamat S, Stellhorn R et al. Analysis of Nationwide Data to Determine the Incidence and Diagnosed Prevalence of Autosomal Dominant Polycystic Kidney Disease in the USA: 2013-2015. Kidney Dis (Basel). 2019 Mar;5(2):107-117. doi: 10.1159/000494923. ↩︎
  2. Cordido A, Besada-Cerecedo L, García-González MA. The Genetic and Cellular Basis of Autosomal Dominant Polycystic Kidney Disease-A Primer for Clinicians. Front Pediatr. 2017 Dec;5:279. doi: 10.3389/fped.2017.00279. ↩︎
  3. Cloutier M, Manceur AM, Guerin A et al. The societal economic burden of autosomal dominant polycystic kidney disease in the United States. BMC Health Serv Res. 2020 Feb;20(1):126. doi: 10.1186/s12913-020-4974-4. ↩︎
  4. PYC Therapeutics. Press release: PYC’s fourth drug candidate has disease-modifying potential in polycystic kidney disease [internet]. Australia: PYC Therapeutics; 2023. Available from: https://www.aspecthuntley.com.au/asxdata/20231113/pdf/02738807.pdf ↩︎
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