Precision medicine company PYC Therapeutics, (ASX: PYC) has filed for patent protection for a precision medicine for the treatment of Diabetic Retinopathy (DR), a leading cause of vision loss in adults aged 20-74 years.
The company also believes its unique treatment has potential for application in neovascular Age-related Macular Degeneration (nAMD).
This drug will become the second program in PYC’s pipeline and is expected to have a rapid path into clinical development due to the ability to leverage both the Cell Penetrating Peptide (CPP) delivery technology and backbone chemistry for the Anti Sense Oligonucleotide (ASO) used in our lead drug programme.
Proliferative retinal diseases (including diabetic retinopathy and nAMD) are characterised by new blood vessel growth in the retina that destroys the retinal tissue and consequently, sight. This new blood vessel growth is caused by a protein called Vascular Endothelial Growth Factor (VEGF). Antibodies that inhibit VEGF are the current gold standard treatment for proliferative retinal diseases and provide exceptional validation of VEGF as a drug target.
Recently, the importance of an additional ‘pro-survival’ role of VEGF has been recognised. VEGF supports the maintenance and viability of delicate cells in the retina, specifically the retinal nerve cells.
VEGF inhibitors successfully stop the destruction of retinal tissue due to new blood vessel growth but they also remove this critical ‘pro-survival’ signal and are suspected of causing the retinal nerve cells to die over time.
A better therapeutic strategy than simply inhibiting VEGF is, therefore, to stop the new blood vessel growth (ie. replicate the outcomes of the current gold standard treatments) whilst retaining the ‘pro-survival’ function of VEGF.
Achieving this outcome would improve the treatment options for the ~50% of Diabetic Retinopathy patients who fail to respond to currently available therapies3.
A mechanism to achieve these objectives has been identified through switching from the ‘pro’ new blood vessel isoform of VEGF protein (VEGF165a) to the ‘anti’ new blood vessel isoform of VEGF protein (VEGF165b) (a protein isoform is coded for by the same gene, but due to different RNA-splicing the proteins have different or opposing functions). This type of approach has recently been recognised in one of the leading ophthalmology journals as an ‘excellent therapeutic strategy.
PYC’s drug candidate acts to promote expression of VEGF165b over VEGF165a during RNA splicing. This therapeutic strategy is known as ‘splice switching’. This increases the proportion of the ‘favourable’ VEGF over the ‘unfavourable’ (‘pro-blood vessel growth’) VEGF.
PYC’s Chief Scientific Officer, Professor Sue Fletcher, said the company will now progress the lead drug candidate into formal pre-clinical efficacy evaluation in the most relevant animal models of proliferative retinal disease (to demonstrate the ‘anti new blood vessel growth’ capabilities of the drug) and/or patient derived cell models (to demonstrate the ‘pro-survival’ capabilities of the drug).
The prospect of a second drug candidate to treat ocular disease and to potentially save the sight of an additional group of patients is a very important development for our team,” Professor Fletcher said.
“The ability to ‘switch’ isoforms is one of the great advantages of antisense oligonucleotide therapeutics, and we are excited that we have been able to leverage this strategy as a potential treatment for diabetic retinopathy and nAMD.”
