Arrowhead Pharmaceuticals Presents New Data On ARC-F12 And ARC-LPA Using DPCsqTM Subcutaneous RNAi Delivery Vehicle

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today delivered oral presentations on ARC-LPA, its preclinical development program targeting lipoprotein (a), for the treatment of cardiovascular disease, and ARC-F12, its preclinical development program targeting factor XII (F12) for the prophylactic treatment of thromboembolism and hereditary angioedema, at the American Heart Association's Scientific Sessions 2016 in New Orleans. These data show advancements being made in the ARC-LPA and ARC-F12 programs and in the development of Arrowhead's proprietary DPC sq TM delivery vehicle designed for subcutaneous administration of RNAi therapeutics.

Chris Anzalone, Ph.D., president and CEO of Arrowhead Pharmaceuticals, said: "We have made rapid advancements to our DPC sq TM subcutaneous RNAi delivery platform. F12 and Lp(a) are both very attractive targets for RNAi, and the data presented today on ARC-F12 and ARC-LPA show substantial improvements in activity over previous generations. In addition, through multiple rounds of SAR studies, substantial gains in potency continue to be made by Arrowhead scientists. Data shown today are from the first and second generation triggers. Studies that are ongoing in NHPs that use our fourth generation RNAi triggers and the DPC sq TM platform, are achieving even higher levels of target knockdown with longer duration using lower and less frequent doses (data not shown)."

The oral poster titled, " Targeting factor XII (F12) with a novel RNAi delivery platform as a prophylactic treatment for thromboembolism", describes advancements in the preclinical development of ARC-F12. Key details of the presentation include the following:
  • F12 is an attractive target for an RNAi therapeutic
    • It is key component at the top of the contact (intrinsic) coagulation cascade
    • It is predominantly expressed in the liver and circulates in blood
    • Inhibition is genetically validated and deficiency protects from thromboembolic disease but is not associated with either bleeding or thrombotic disorders
  • Arrowhead developed RNAi triggers that gave greater than 95% reductions of serum F12 levels after a single subcutaneous injection
  • Dose dependent reductions in serum F12 levels were observed with single injections of ARC-F12 of 1 mg/kg and 3 mg/kg leading to mean reductions of 86% and 96% respectively
  • A statistically significant reduction (p=0.002) in thrombus weight was observed at greater than 95% F12 knockdown in a rat arterio-venous shunt model
  • There was no increased bleeding risk in ARC-F12 treated mice, even with greater than 99% knockdown of F12 levels

The oral presentation titled, " Targeting apolipoprotein(a) with a novel RNAi delivery platform as a prophylactic treatment to reduce risk of cardiovascular events in individuals with elevated lipoprotein (a)", describes advancements in the preclinical development of ARC-LPA, which is part of a recently announced license and collaboration agreement with Amgen. Key details of the presentation include the following:
  • Lipoprotein (a) [Lp(a)] is an attractive target for an RNAi therapeutic
    • Lp(a) is an independent risk factor for cardiovascular disease through its atherogenic potential
    • Higher levels of Lp(a) correlate with increased risk of cardiovascular disease
    • Lp(a) levels in humans are genetically defined and do not change significantly with diet and exercise
    • Approximately 25% of the U.S. population has greater than 30 mg/dL of Lp(a) (normal levels: 0.1 - 25 mg/dL)
    • It is predominantly expressed in the liver and circulates in blood
  • Screening of LPA RNAi triggers in Lp(a) transgenic (Tg) mice identified several that induced substantial and sustained knockdown of serum Lp(a) levels
  • Structure activity relationship (SAR) studies assessing structure and chemical modifications identified triggers that achieved greater than 98% maximum knockdown after a single 3 mg/kg SQ dose in Tg mice
  • In NHPs, 85-90% reduction of serum Lp(a) levels was observed after three weekly 3 mg/kg SQ doses
  • In an atherosclerosis model, data suggest that RNAi triggers can be effectively delivered to a fatty liver using the DPC sq TM platform

A copy of presentation materials will be made available on the Events and Presentations page under the Investors section of the Arrowhead website.

About ARC-F12

Arrowhead's RNAi-based candidate ARC-F12 is in preclinical development as a potential treatment for factor XII (F12) mediated diseases. Arrowhead sees clear unmet need in hereditary angioedema (HAE) and thromboembolic diseases. The biology of factor 12 as part of the coagulation cascade and the kinin-kallikrein system suggest that its reduction through RNAi may present opportunities in both disease areas. The company is currently conducting studies in order to advance ARC-F12 into clinical trials.

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