Reaching previously unreachable intracellular targets
Our Science
The Problem
The highest value drug targets exist within the cell, including DNA, RNA, and many proteins. Numerous diseases can be corrected through intracellular interventions such as rare genetic disorders, certain cancer genes (oncogenes) and processes, and cardiovascular diseases. These high-value targets are protected by a formidable barrier; the cell membrane, which has evolved over millions of years to keep foreign molecules out, including drugs.
These high-value targets often require a large molecule to correct the disease, such as a gene in gene therapy, antisense oligonucleotide in RNA therapy, or CRISPR-Cas9 in gene editing. These are the type of molecules the cell wall specialises in keeping out, meaning many of these drugs face a significant challenge - they cannot get inside the cell where they are needed.
Our Solution
PYC Therapeutics has a next-generation delivery platform to overcome this barrier, cell-penetrating peptides (CPPs). CPPs are short chains of amino acids known as peptides, which due to their sequence and properties, can deliver drugs across a cell membrane. Despite much research and significant investment, the biotechnology industry has identified only a few safe, functional CPPs.
PYC Therapeutics has leveraged its proprietary peptide libraries, which contain billions of peptide fragments from diverse and evolutionarily distinct microbial genomes - organisms which have known cell-penetrating properties.
Combined with our proprietary high throughput screening and advanced analytics, PYC can identify safe, high efficacy, and specific CPPs.
Our Results
As part of our flagship ocular program, PYC has been able to demonstrate outperformance compared the current gold standard CPP by 400% in a mouse model (see fig 1.) and effective delivery in human cells (see fig 2.)
Our Therapeutic Application
PYC Therapeutics is combing its breakthrough CPP platform with world-leading expertise in next-generation Antisense Oligonucleotides (ASOs) to create a pipeline of drugs known as CPP-ASOs. Our initial focus is to deliver to market a CPP-ASOs which treats an Inherited Retinal Disease called Retinitis Pigmentosa, the leading cause of childhood blindness.
ASOs are a leading RNA therapeutic, with 2 significant ASO drugs on the market: Biogen's Spinzara for Spinal Muscular Atrophy, and Sarepta's Exondys 51 for Duchene's Muscular Dystrophy. ASOs correct disease before it presents, including through correcting a protein deficiency or toxicity - it turns the problem off at the tap rather than just mopping up the water like many modern drugs.
ASOs correct genetic coding errors by using the cells exisitng machinery. In the human body, all our cells and their proteins are encoded in our DNA which makes up our genes and genome. DNA is transcribed into another molecule called RNA, which is a copy of the DNA the cell uses as instructions to make proteins. If you have a mutation in your gene, this mutation will be copied across to your RNA, and then your cell will not have the right instructions, and so it might not make the right protein. The creation of these non-functional proteins cause the genetic disease.
ASOs are a molecule which is somewhat similar to RNA in that is has the same 'chemical instructions'. These ASOs bind to the RNA before it's used to make protein and alter the RNA's instructions to the cell to produce health, or functional, protein.