Ann: FNA Presentation, page-19

OK, I asked the company about the graph and the concerns expressed here. Here's the reply, with some minor amendments.

• The lower the concentration, the greater the outperformance of Phylogica's CPPs over 'conventional' CPPs.

• This isn’t well represented in the page from the FNA presentation - this is a function of the sensitivity of the assay at lower concentrations rather than evidence of better performance of the 'conventional' CPPs.

• The 1, 2 and 4 micromolar readings in the graph show a nice relationship between higher concentration and greater effect - this effect does not hold for the sub-1 micromolar concentrations indicating the loss of sensitivity of the assay at these concentrations.

• One can better see comparisons in the sub 1-micromolar range in some of PYC’s older materials (see graph below)

• Here, the 'conventional' CPPs are not effective at all below 1 micromolar (no positive results were recorded at all hence their exclusion from the key) and seem to 'step up' significantly at higher concentrations (much bigger than the increment for PYC's CPPs at higher doses) indicating a change in mechanism of action (possibly due to forming holes in the cell wall that may well lead to toxicity).

• With respect to therapeutically relevant concentrations, that is an indication specific question. The Feldan evaluation of their 'shuttle' for delivery of Cas9 evaluated doses of between 4 and 35 micromolar, for example. Given PYC’s CPPs have relatively greater outperformance at lower doses, they have a greater competitive advantage the lower the administered dose - ie. the lower you have to go, the more favourable the setting for PYC's CPPs versus 'conventional' CPPs.

• The more relevant question is whether PYC can get enough cargo inside the cell to correct the absolute threshold of disease and that is the issue that the company is interested in addressing through the upcoming in vivo therapeutic read-outs.