* PYC have addressed the major hurdle in the pre-clinical development of their platform.
* They've successfully demonstrated that their first generation CPPs can deliver ASOs inside cells to reach their target across multiple tissue types in an animal.
But it was these two paragraphs below that stood out for me. Why?
"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." and...
"The results shown below in Figure 1 represent a read-out of two versions of mRNA transcripts from organ homogenates harvested 4 days after a single intravenous injection of 20mg/kg CPP-ASO. Successful delivery of the ASO by the CPP is reflected in an mRNA transcript for a shortened (truncated) version of the protein." 1. More research on my behalf, but I'm interested in knowing what the protein is that's produced by all cells in the body. Allows evaluation across all types of tissues. Amazing.
2. 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.
3. One single intraveneous injection of 20mg/kg CPP-ASO. I'm very encouraged by this data. Why? Looks to me like its a low dose, based on the company's first generation CPPs. How does PYC's flagship program compare to other programs? Have a read of this article below.
https://musculardystrophynews.com/2018/05/14/new-exon-51-skipping-therapy-for-dmd-srp-5051-explained-by-sarepta-cmo-in-webinar/ 4. The the platform becomes very scaleable based on the reporter ASO and the success of program of course. Can't wait until they switch from the 'reporter' ASO to the 'therapeutic' ASO.
"Transition from the ‘reporter’ ASO described here to therapeutic ASOs is a rapid process with ahigh degree of reproducibility of result. These models are, therefore, a good indicator of ourprospects of success in in vivo therapeutic models."5. Page 6...
"Therapeutic in vivo outcomes are the primary reference point for Pharma partners assessing whether pre-clinical (animal) outcomes will translate into clinical (human) outcomes."https://phylogica.com/wp-content/uploads/2018/11/181116_AGM-Company-Presentations_1871405.pdf Tony
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