RP11

Retinitis Pigmentosa type 11
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DISEASE OVERVIEW

RP11 is a devastating, progressive and blinding eye disease caused by under-expression of the PRPF31 gene.

Patients experience vision changes from childhood, leading to legal blindness by 40–50 years of age. Disease management consists of visual aids and genetic counselling, but there are currently no available treatments for RP11 that treat the course of the disease.

PYC has developed VP-001, a therapy that addresses the underlying genetic cause of RP11 and has achieved breakthrough pre-clinical results in the rescue of the appearance of affected retinal cells in patient-derived models. VP-001 is the first drug candidate to enter clinical trials for RP11 and is currently in a mid-stage clinical study in RP11 patients. VP-001 has provided promising safety and efficacy insights from RP11 patients dosed in this Phase 1 study.

Our patients

“As I become increasingly blind, there are countless changes and losses. I try to mentally prepare myself for some of the harder losses that I know are coming. But, I simply cannot bring myself to imagine a world in which I cannot see my young daughters' smiles when they come in for a "running hug." PYC may allow me to avoid ever facing a world in which I cannot see their smiles.”

Christine, RP11 patient
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RP11 at a glance

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

RP11 affects 1 in every 3,500 people.1,2

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.

RP11 is a monogenic disease

RP11 is caused by a mutation in one of the patient’s two copies of the PRPF31 gene; this mutation causes insufficient production of the PRPF31 protein, which is required for normal retinal function.

An icon of a navy blue eye with an orange diagonal slash across the front of it from the top right corner to the bottom left corner.

Loss of central vision and legal blindness

Patients with RP11 initially experience night blindness, followed by tunnel vision and ultimately loss of central vision and legal blindness.

An icon of a navy blue double-helix of DNA tilted on an angle from the top right corner to the bottom left corner. This DNA has a clear circle with an orange outline around it.

PYC's drug candidate, VP-001, seeks to stop disease progression

RP11 patients have a mutation in one copy of the PRPF31 gene – this leads to their retinal cells producing half as much PRPF31 protein as is required for normal function. VP-001 seeks to restore the production of PRPF31 protein in patients, therefore rescuing function of retinal cells and thus stopping disease progression.

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Encouraging results

VP-001 is currently in mid-stage clinical trials treating RP11 patients, which have provided early safety and efficacy results.

RP11 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 'RP11 patient DNA'.

Genetic mutation

RP11 patients have a mutation in one of their two copies of the PRPF31 gene – this mutation is present in all the cells in their body but has a significant effect in the retinal cells of the eye, causing the loss of function of these cells that are necessary for sight.

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 PRPF31 protein chains. On the right, one strand is orange and one is blue within the pair. It is titled 'RP11 patient'. There is a white arrow below this pair pointing down towards one strand of PRPF31 protein chain and a white bubble containing the text '-50%'.

Decreased protein production

The PRPF31 gene mutation creates an unstable RNA message – this leads to the gene producing approximately half as much PRPF31 protein as is required to function normally. PYC’s therapeutic, VP-001, seeks to increase protein expression in the remaining healthy copy of the PRPF31 gene to restore PRPF31 protein production to levels that are sufficient for the cells to function.

An sagittal cross-section infographic of an eye. The retina is depicted in white at the back of the eye and is peeling away into the centre of the eye. This is titled 'Deteriorating retina'.

Cellular changes

Underproduction of the PRPF31 protein causes photoreceptor cells in the retina to lose function and ultimately die. These photoreceptor cells are responsible for detecting light that enters the eye and are dependent on the PRPF31 protein to function normally.

 

VP-001 has disease-modifying potential to halt cellular changes and arrest disease progression – it’s a potentially life-changing therapeutic.

An icon of a white eye with an orange diagonal slash through it.

Patient symptoms

As the number of photoreceptors in the eye decline, RP11 patients experience changes in their vision, including night blindness and deterioration of peripheral vision, ultimately progressing to legal blindness.

 

At PYC, we aim to eradicate the development of RP11 symptoms with our first-in-class drug candidate, VP-001.

The human impact of RP11

RP11 leads to degenerative sight changes, beginning in childhood.
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6 years old

At first, a child is noticed to be clumsy, especially at night.

A photo of a beach with a cityscape in the background. There are two black swans standing in the foreground on the beach. However the image is darker and difficult to see and the centre and corners of the image are completely black.

26 years old

Over time, patients experience night blindness and increasing tunnel vision as their peripheral vision begins to decline.

A black square.

46 years old

Patients are diagnosed with legal blindness around 40–50 years of age, which significantly impacts their quality of life.

VP-001 is a potentially life-changing treatment

VP-001 is a molecular therapeutic that targets the underlying PRPF31 gene mutation and aims to increase PRPF31 protein production back to levels sufficient for cell function. VP-001 is designed to halt the progression of the disease in RP11 patients and enable them to retain their sight.

In-vitro experiments demonstrate the ability of VP-001 to restore PRPF31 expression to levels seen in unaffected people – demonstrating the potential for VP-001 to restore gene expression in patients.

A bar graph containing three bars. The y-axis is titled 'PRPF31 expression'. The left bar is titled 'Unaffected' and reaches a value of approximately 1.0. The middle bar is titled 'Untreated RP11 cells' and reaches a value of approximately 0.7. The right bar is titled 'RP11 cells + VP-001' and reaches a value of approximately 1.2.
*PRPF31 mRNA expression in RP11 iPSC-RPE as measured by ddPCR (PRPF31_ex3–4 normalised to HPRT1 and SENP5). Student's t-test. **=p<0.0001.
A table that contains three columns titled 'Unaffected individual', 'RP11 patient' and 'RP11 patient + VP-001' 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 PRPF31 protein, these are labelled '100%'. In the 'RP11 patient' column there is dark blue and orange DNA, one strand of dark blue and one strand of orange RNA and one strand of PRPF31 protein, labelled '~50%'. In the 'RP11 patient + VP-001' column there is dark blue and orange DNA, one strand of dark blue and one strand of orange RNA and two strands of PRPF31 protein, these are labelled 'up to 100%'.

RP11 retinal cells in 'retina in a dish' models

With recent advances in technology, PYC can grow retinal cells of RP11 patients – using ‘retina in a dish’ models – and treat them with VP-001 to test its efficacy. Retinal cells derived from an RP11 patient and treated with VP-001 demonstrate the ability to rescue the appearance and function of RP11 retinal cells in these patient-derived models.
A black and white image of some retinal eye cells in a person who does not have RP11. All of the cells are sitting tightly next to each other.

An 'unaffected' individual

A black and white image of some retinal eye cells in a patient with RP11. There are large spaces between many of the cells.

A patient with RP11

A black and white image of some retinal eye cells in a patient with RP11 who has received a single dose of VP-001. All of the cells are sitting tightly next to each other.

A patient with RP11 after a single dose of VP-001

RP11-affected retinal cells treated with VP-001 visibly improve in appearance, resembling retinal cells from unaffected people.

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. Daiger P, Bowne SJ, Sullivan LS. Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa. Cold Spring Harb Perspect Med. 2014 Oct;5(10):a017129. doi: 10.1101/cshperspect.a017129. ↩︎
  2. Sullivan LS, Bowne SJ, Seaman CR et al. Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4579–88. doi: 10.1167/iovs.06-0440. ↩︎
  3. PYC Therapeutics. Press release: commencement of RP11 multiple dose trial [internet]. Australia: PYC Therapeutics; 2024. Available from: https://www.aspecthuntley.com.au/asxdata/20240710/pdf/02826505.pdf ↩︎
  4. PYC Therapeutics. Press release: bioshares biotech summit presentation [internet]. Australia: PYC Therapeutics; 2024. Available from: https://www.aspecthuntley.com.au/asxdata/20240712/pdf/02827325.pdf ↩︎
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