Arrowhead Research Corp (NASDAQ:ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, announced that it completed dosing healthy volunteers and will begin dosing patients in an on-going phase 1 study of ARC-AAT, the Company’s clinical candidate for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD). AATD is a rare genetic disorder that can severely damage the liver and lungs of affected individuals. The study was designed to begin dose escalation in healthy volunteers (Part A) and transition into patients (Part B) when a predefined knockdown target is achieved. That target is at least 30% reduction of serum AAT levels in 3 subjects or greater than 60% reduction in a single subject. This was met during the third cohort. All three dose levels tested appear to be generally well tolerated and the data safety committee has cleared the study to move into patients with AATD. Dosing in patients may now begin at the highest dose level used in Part A and then continued dose escalation may proceed under the protocol. The company expects to complete the Phase 1 study by the end of 2015.

“We are excited that Part A of the phase 1 study is complete and that we can now begin studying ARC-AAT directly in patients with PiZZ genotype AATD,” said Bruce D. Given, M.D., Arrowhead’s Chief Operating Officer. “The lung disease associated with AATD is frequently treated with AAT augmentation therapy. However, there is a great need in the field to identify new treatment options for the AATD-related liver disease. Currently, the only option for severe cases is liver transplant, with all of its attendant risks and availability issues. We think ARC-AAT is a very promising program that may potentially provide a better option for patients and physicians.”

ARC-AAT is comprised of novel unlocked nucleobase analog containing RNAi trigger molecules (UNA) that are co-administered with Dynamic Polyconjugates (DPCs) to enable the escape of the UNA from endosomes. The ratio of UNA to DPC is 2:1 by weight. In Part A of the study, three cohorts of six participants each received ARC-AAT at doses of 0.38 mg/kg, 1.0 mg/kg, and 2.0 mg/kg of UNA, and 0.19 mg/kg, 0.5 mg/kg, and 1.0 mg/kg of DPC, respectively.

The Phase 1 trial is a multi-center, randomized, placebo-controlled, double-blind, single dose-escalation first-in-human study to evaluate the safety, tolerability and pharmacokinetics of ARC-AAT and the effect on circulating AAT levels. The study has been enrolling in dose cohorts of six participants each, with participants randomized at a ratio of 2:1 (active:placebo) to receive a single intravenous injection of either ARC-AAT or placebo (normal saline). The study consists of two parts; Part A in healthy volunteers, which has been completed, and Part B to be conducted in patients with PiZZ genotype AATD. The study evaluates participants for 28 days following dosing, with additional follow-up if needed every 2 weeks until AAT levels return to baseline.

“The Alpha-1 Foundation and the entire Alpha-1 community are excited to see this program move forward,” said John Walsh, president and chief executive officer of the Alpha-1 Foundation. “We and The Alpha-1 Project, the Foundation’s venture philanthropy arm, will continue to work closely with Arrowhead on clinical trial recruitment and provide additional assistance to get this potentially life saving therapy to adults and children with liver disease due to Alpha-1.”¬†(Original Source)

Shares of Arrowhead closed yesterday at $6.94 . ARWR has a 1-year high of $17.42 and a 1-year low of $4.95. The stock’s 50-day moving average is $7.26 and its 200-day moving average is $6.78.

On the ratings front, Arrowhead¬†has been the subject of a number of recent research reports. In a report issued on April 14, Jefferies Co. analyst Thomas Wei downgraded ARWR to Hold, with a price target of $9, which represents a potential upside of 29.7% from where the stock is currently trading. Separately, on January 22, Deutsche Bank’s Alethia Young downgraded the stock to Hold and has a price target of $7.

According to, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Thomas Wei and Alethia Young have a total average return of 12.6% and 10.2% respectively. Wei has a success rate of 60.2% and is ranked #309 out of 3589 analysts, while Young has a success rate of 52.5% and is ranked #868.

Arrowhead Research Corp is engaged in developing novel drugs to treat intractable diseases by silencing the genes. The Company’s drug candidate ARC-520 is designed to treat chronic hepatitis B infection.