PYC - General Discussion, page-16

My recollection is that the drugs for RP11 and ADOA, although distinct oligonucleotide drugs both use the same cell penetrating peptide. However I note that in the E & P report it is stated that each asset uses a different CPP.

Certainly, the RP11 and ADOA drugs both target the retina, but different cell layers –the RP11 asset (VP-001) targets retinal pigment epithelium cells whereas the ADOA asset (PYC-001) targets retinal ganglion cells. Both eye drugs are administered via intravitreal injection.

The ADPKD drug is a different oligonucleotide and a different CPP – one that has been chosen because it is preferential to the kidney but also slightly to the liver, where cysts can also develop from ADPKD. This drug will use i.v. administration which will present a different risk profile to the eye drugs.

The Phelan-McDermid asset is different again. Two initial versions have been developed – one uses a different CPP whereas the other is a naked antisense (one with no CPP). Each has its own advantage/disadvantage profile. Whichever PMS drug is used, it will be administered into the brain using intrathecal delivery (lumbar puncture).

So, similar in that all are PMO antisense drugs, but different in the PMO used, the CPP used (or not used), the target cells and in route of administration.

One other similarity that is shared by this pipeline of drugs is a much higher probability of success in clinic than standard drugs because all PYC pipeline drugs target monogenic diseases and all will undergo rigorous preclinical testing, including use of human disease models.