"1 The reference peptide for clinical development is an oligo-arginine peptide with a chemically stabilised backbone (RXR4). The peptide resembles a CPP known as ‘PepK’ which represents the CPP with the greatest body of evidence to support clinical development of Anti-Sense Oligonucleotide delivery."
* PYC’s CPPs performed substantially better than the current CPP benchmark for clinical development. You might want to do some research as to who is using the RXR4 peptide in a pre-clinical setting.
Phylogica's objective with regards to their CPP platform is all about delivering a drug to a targeted tissue, a target cell within a tissue and a target location within a cell. What does the company need to achieve in order for their delivery platform to be successful? As SoT highlighted, a 30-60 x increase in cargo to correct a disease process occurring within a cell.
* PYC have demonstrated that their second generation CPPs can achieve the objective of delivering a sufficient amount of cargo inside animal cells in a safe manner - that's the major pre-clinical milestone in the development of their platform.
"Therapeutic in vivo outcomes are the primary reference point for Pharma partners assessing whether pre-clinical (animal) outcomes will translate into clinical (human) outcomes"
* PYC will now evaluate the remainder of their 2nd generation CPP candidates in human retinal cells and animal models as they progress to selection of their leads for clinical development.
At the time of the announcement below (March 2019), I was interested in understanding what the protein produced by all cells in the body was.
"The reporter ASO, when effectively delivered to its target inside the cell, causes the production of a shortened version of a protein that is produced by all cells in the body (allowing evaluation across all types of tissue). The ratio of the mRNA coding for the shortened version of the protein (indicating successful exon skipping by the ASO in the cell’s nucleus) to the mRNA coding for the full-length protein is then used as an objective measure of the functional efficacy of the CPP-ASO molecule.
All routes of administration demonstrated effective exon skipping in the target tissues harvested following administration. The systemic injection resulted in exon skipping in the eye, liver and kidney (with other tissues harvested yet to be processed). The intra-vitreal injections resulted in exon skipping in the anterior and posterior segment of the eye."
The reporter protein is the Survival of Motor Neuron 1 protein (SMN1) as highlighted on page three in yesterday's announcement.
"Transition from the ‘reporter’ ASO described here to therapeutic ASOs is a rapid process with a high degree of reproducibility of result. These models are, therefore, a good indicator of our prospects of success in in vivo therapeutic models."(BIG tick).
1. It was able to deliver the ASO cargo in three different segments of the eye.
2. It was able to do so at a single dose of 1.6 micrograms per eye at 5 days post-administration (a dose that is substantially lower than competitive approaches).
3. Successful exon skipping by the ASO in the cell's nucleus. So the higher the doses without compromising safety, the higher the percentage of exon skipping which means the CPP-ASO has gotten to its target.
4. There was no toxicity observed even at a dose of 30mg/kg in a separate mouse model, whereas the clinical benchmark peptide demonstrated toxicity when administered at the lower dose of 20mg/kg.
5. PYC's platform technology has the potential to scale across many other areas of high unmet medical need (priority indications in other tissues include motor neuron disease in the brain).
You may also be interested to have a look at what the company Stoke Therapeutics are targeting.
Tony
PYC Price at posting:
2.9¢ Sentiment: Buy Disclosure: Held
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