Ann: Fourfold Delivery Improvement in a New Lead Candidate, page-46

Hi Andrew,

In my view, I think the market has underestimated the results re TAT outperformance.

https://thewest.com.au/business/public-companies/phylogica-makes-new-drug-delivery-discovery-ng-b881005715z

One of the challenges with TAT fused cargoes is that they are inefficient at delivering the particular cargo and thus remain trapped within the endosome. It's imperative to get the cargo inside the the cell to reach its target, not the endosome. That's why I mentioned that improving the hit rate for cell specific CPPs is extremely important, as TAT peptides are non specific and cell specificity is critical. Toxicity is the other important factor when non cell specific CPPs are in question. Why? Because they are distributed throughout the whole body and not to the diseased target. Therefore they're much more likely to show side effects due to the cargo itself. The point about toxicity was nicely summed up in the last paragraph in this announcement below. If you recall, these were for the BEN peptides. I can only imagine how things may potentially improve hit-rate wise now that high throughput screening at scale is in play.

https://phylogica.com/wp-content/uploads/2017/10/171004_PYC-Granted-US-Patent-for-Peptides-Entering-Brain-Cells_1722426.pdf

Now coming back to the Cre enzyme, the company was able to deliver i.e. the cargo into the nucleus of the cell across many different tissue types and that was using peptide CPP1 in vivo. That was all pre high throughput screening. That's very exciting imv. Delivery of cargo into different tissues and cell types is the first step. Then there's the work on peptide CPP2 in vitro, which appears to be twice as effective as CPP1, which will be tested in the same animal model in vivo. Any improvement in the CPPs from here and things could get very interesting.

https://phylogica.com/wp-content/uploads/2018/07/180730_Achievement-of-Major-Milestone-In-vivo-Cre-Delivery1824712.pdf

Tony