Something for everyone, page-5

Thanks for posting the article ds.
In the article it mentions Arrowhead Pharmaceuticals, a company that claimed to have endosome escaping technology. In 2016 Arrowhead dropped their three clinical programs that included endosome escape due to toxicity. In the article, it shows Arrowhead have been using a pore-forming melittin peptide obtained from bee venom (for endosome escape).
Our mate in the other chat room, has believed Arrowhead was using Phylomer IP. This is obviously not the case with Phylomer libraries being sourced from microbes.
from the Nature.com article:
Arrowhead Pharmaceuticals developed a two-molecule dynamic polyconjugate (DPC) system¹⁰³. The siRNA is conjugated to cholesterol, which forms a large aggregate (low-density lipoprotein) in blood that is transported to the liver and taken up by endocytosis into hepatocytes. The second molecule is a derivative of the pore-forming melittin peptide (derived from bee venom) that lyses membranes¹⁰⁴. To tame melittin, Arrowhead synthesized it with pH-sensitive protecting groups and conjugated it to GalNAc. In the low pH of hepatocyte endosomes, melittin is deprotected, becomes active and lyses the endosome to release the siRNA into the cytoplasm (Fig. 4). Unfortunately, owing to toxicity likely from the melittin, Arrowhead had an FDA clinical hold placed on their lead program and decided to drop all three clinical programs that rely on melittin to escape the endosome¹⁰⁵. The inclusion of an endosomolytic molecule as powerful and potentially toxic as melittin shows the degree of difficulty required to address the endosomal escape problem.

To date PYC's tox studies appear to be in line with their expectations. In their last update it's shown they have achieved their goal for the POC:
Evidence of maintenance of viability for FPP vs FPP-cargo at micromolar concentrations in-vitro.
In the Murdoch Uni work, tox is also high focus.
from PYC shareholder update:
Last quarter, we reported that preliminary IV animal experiments showed evidence of efficacy and low-toxicity in the delivery of exon-skipping oligonucleotides in models of both Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) to muscles in a range of locations (including cardiac, diaphragm and tibia). Further animal experiments and analysis are underway to reinforce the evidence of lower toxicity of FPPs versus other CPPs.
SoT