Arrowhead Says ARC-LPA Achieved 98% Knockdown, Long Duration of Effect After Subcutaneous Admin

Arrowhead Pharmaceuticals, Inc.

today presented a poster on ARC-LPA, its preclinical development program targeting lipoprotein (a), or Lp(a), for the treatment of cardiovascular disease at the Arteriosclerosis, Thrombosis and Vascular Biology | Peripheral Vascular Disease (ATVB|PVD) 2016 Scientific Sessions in Nashville. ARC-LPA is the first RNAi therapeutic program to use Arrowhead's new delivery vehicles designed for subcutaneous (SQ) administration. Chris Anzalone, Ph.D., president and CEO of Arrowhead Pharmaceuticals, said: "These data are exciting for several reasons. First, they represent continued progress in our SQ delivery platform, creating opportunities to address various diseases that require chronic treatment and where SQ administration may be preferable for patients and physicians. We are enabling very deep target gene knockdown with long duration of effect that may enable monthly, bi-monthly, or even less frequent administration. Second, reducing Lp(a), as we have seen now in multiple animal models, could represent an important leap forward in the treatment of cardiovascular disease. High levels of Lp(a) are associated with increased risk of cardiovascular disease independent of cholesterol and LDL, and there is currently no good way to deeply reduce circulating levels of Lp(a)." The poster titled, "Lipoprotein(a) targeting with RNAi delivery platforms in transgenic mice and cynomolgus monkeys" (presentation 428), describes data from in vitro screening of RNAi triggers and multiple in vivo models, including transiently transgenic mice, transgenic mice (Tg), and non-human primates (NHPs). Key findings from these studies include the following: Screening of RNAi triggers in Tg mice identified those that exhibited substantial and sustained knockdown of serum apo(a) and Lp(a) levels RNAi trigger sequences were active in both intravenous and SQ platforms Structure activity relationship (SAR) studies looking at chemical modifications to the RNAi trigger identified a lead that demonstrated greater than 98% maximum knockdown after a single 3 mg/kg SQ dose in transgenic mice Duration of effect gains were also made with greater than 85% knockdown still seen at 6 weeks post dose In NHPs, 85-90% reduction of serum Lp(a) levels was observed after three weekly 3 mg/kg SQ doses Duration of effect in NHPs was long, with Lp(a) levels still reduced by 75% 6 weeks after the final dose A copy of the poster presentation will be made available on the Events and Presentations page under the Investors section of the Arrowhead website.