Ann: Kidney Disease Drug Candidate Progressing to Human Trials, page-18

Some interesting points from E & P's note today as the results were better than anticpated:

• To put this result into context: Sarepta’s (NASDAQ:SRPT) drug candidate (SRP-5051; a similar peptide-conjugated oligonucleotide to PYC-003) for Duchenne muscular dystrophy (DMD) also showed a dose dependent and sustained exposure persisting for 28 days, but from double the initial dose (60 mg/kg) and at fraction of the concentration in muscle tissue (~500 ng/mL) that PYC observed in the kidneys at an equivalent time point (>30,000 ng/mL; the actual concentration was above the quantitation limit of the assay).
• Importantly, SRP-5051 at this markedly reduced PD profile to PYC-003 was able to generate ~20% exon skipping.
• Based on these data, PYC-003 could achieve day-30 target tissue concentrations orders of magnitude greater than SRP-5051.
• Obviously PKD and DMD are different conditions in different target organs, but the pharmacodynamic implications of this comparison are relevant and encouraging.
• Taken together, this suggests that PYC-003 could be dosed and tolerated well above the putative therapeutic range (1 – 5 mg/kg), achieving impressive target tissue concentrations, with significant safety headroom.