Replies to post #226053 on Biotech Values

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ARO-ENaC rat poster...

Targeting aENaC with an Epithelial RNAi Trigger Delivery Platform for the Treatment of Cystic Fibrosis

CONCLUSIONS

•EpLintegrin avb6 receptor ligands improve endocytosis of RNAi triggers in cultured epithelial cells

•EpLconjugates employing ligands to the integrin avb6 receptor improve functional delivery of an aENaCRNAi trigger to the pulmonary epithelium after inhalation, producing deeper and more consistent reduction of whole lung aENaCmRNA at lower doses

•Loss of airway epithelial aENaCprotein expression is observed at exposures that produce ~50% reduction in whole lung aENaCmRNA, with remaining protein expressed in alveolar epithelium

•Reduction of lung aENaCmRNA expression is durable, maintaining >50% knockdown at 3 weeks post-dose and requiring 6-7 weeks for recovery to baseline expression

•Aerosol inhalation improves delivery efficiency of EpL-aENaCRNAi trigger conjugates approximately tenfold over intratracheal administration

•EpL-aENaCRNAi trigger conjugates are well-tolerated with no observed changes in renal aENaCmRNA expression

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ARWR > shows 3-6 month dosing possible using RNAi for dyslipidemias...

Arrowhead Pharmaceuticals Presents Initial Top-Line Clinical Data and Preclinical Data on RNAi Candidates ARO-APOC3 and ARO-ANG3

slide deck...http://ir.arrowheadpharma.com/static-files/ebe9c688-444c-43d4-97e6-bb4393652862

The data demonstrate that, in two Phase I single-dose clinical studies in healthy volunteers, ARO-APOC3 reduced plasma Apolipoprotein C-III (apoC-III) and ARO-ANG3 reduced plasma angiopoietin like protein 3 (ANGPTL3), and both candidates reduced triglycerides without drug-related serious or severe adverse events. These initial clinical data also indicate that ARO-APOC3 and ARO-ANG3 administration led to a long duration of effect that potentially enables once every three-month or once every six-month dosing intervals.

Top-line data from a single dose of 100 mg of ARO-APOC3 in healthy volunteers demonstrated mean maximal reductions of plasma triglycerides of 63% and APOC3 protein of 94% without serious or severe adverse events
The most common adverse events observed to date, all mild or moderate, have been headache, upper respiratory infection and mild injection site findings

Top-line data from a single dose of 200 mg of ARO-ANG3 in healthy volunteers demonstrated mean maximal reductions of plasma triglycerides of 66% and ANGPTL3 protein of 79% without drug-related serious or severe adverse events

The most common adverse events seen to date, all mild or moderate, have been headache and upper respiratory infection