Arrowhead Completes Enrollment in Phase 1 Study of ARC-520 for the Treatment of Chronic Hepatitis B

  Arrowhead Completes Enrollment in Phase 1 Study of ARC-520 for the Treatment
  of Chronic Hepatitis B

    - Safety and tolerability support advancement of ARC-520 into Phase 2a

Business Wire

PASADENA, Calif. -- October 8, 2013

Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company
developing targeted RNAi therapeutics, today announced that it completed
enrollment in a Phase 1 clinical trial of ARC-520, its RNAi-based candidate
against chronic hepatitis B virus infection. Initial data indicate that
ARC-520 is generally safe and well tolerated at all six dose levels studied,
enabling the company to proceed with plans to initiate a Phase 2a pilot
efficacy study in chronic HBV patients.

“We are very pleased with these results and the pace at which we were able to
complete the Phase 1 study. This positive readout on safety and tolerability
of ARC-520 and the Dynamic Polyconjugate (DPC) delivery platform has broad
implications for Arrowhead. It gives us additional confidence as we move into
an upcoming Phase 2a study and we believe it represents a key de-risking event
for expanding our pipeline of RNAi therapeutics based on the DPC platform,”
said Christopher Anzalone, Ph.D., President and Chief Executive Officer.

The Phase 1 trial was designed to characterize the safety profile of ARC-520
across a range of doses and evaluate pharmacokinetics. It is a single-center,
randomized, double-blind, placebo-controlled, single dose-escalation,
first-in-human study of ARC-520 administered intravenously to healthy adult
volunteers. All subjects have been dosed and received either placebo or
ARC-520 in doses ranging from 0.01 mg/kg to 2 mg/kg.

The study was planned to enroll 36 subjects in six cohorts of six subjects
each, with 2 subjects receiving placebo and 4 receiving ARC-520.The study
successfully enrolled all 36 subjects (24 received ARC-520, 12 placebo) at a
single center in Melbourne, Australia.All subjects received their full,
assigned dose and there were no discontinuations for adverse events or
otherwise.

Based on pre-clinical studies, including GLP toxicology, it is expected that
if any clinically significant or dose-limiting toxicities were to occur, they
would be observed within the first 24-48 hours after administration, and would
be apparent in elevations in blood chemistries. The anticipated organs of
interest for potential toxicity and the resultant chemistries are liver (ALT),
kidney (creatinine, urea), and muscle (CK, AST, LDH, Troponin I). In this
Phase 1 study, laboratory results have not indicated any organ toxicity
involving the liver, kidney, or muscle in any subject.

There have been no serious or severe adverse events reported in any
subject.Overall, adverse events have been consistent with those typically
seen in normal volunteer studies, including in placebo subjects. The most
common events reported were upper respiratory infection (7), which were not
unexpected as the trial was enrolled during the Australian winter, and
headache (7).The only other events reported in more than one subject were
mild lightheadedness (2), which were not accompanied by any changes in vital
signs, laboratories or physical examinations. One subject developed an
urticarial rash with no other physical findings, and was treated successfully
with anti-histamine. Adverse events appear to have been randomly scattered
across all six dosing groups with no apparent dose-related increases in
occurrence rate or severity with the possible exception of mild
lightheadedness.Both subjects with mild lightheadedness were in the 2 mg/kg
group.Laboratory abnormalities have occurred sporadically across groups and
time points pre- and post-dosing.None of these indicate any organ toxicity
and the frequency and severity do not appear to be dose-related.

The study remains blinded and follow-up is ongoing. Arrowhead intends to
report additional data including pharmacokinetics and relative occurrence
rates for adverse events in placebo and ARC-520 treatment groups at an
appropriate venue when those data become available. The company plans to use
the blinded analysis available now to move forward with a filing seeking
approval to proceed with a Phase 2a trial in Hong Kong.

About ARC-520

Approximately 350 million people worldwide are chronically infected with the
hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the liver
and is responsible for 80% of primary liver cancers globally. Arrowhead’s
RNAi-based candidate ARC-520 is designed to treat chronic HBV infection by
reducing the expression and release of new viral particles and key viral
proteins. The goal is to achieve a functional cure, which is an immune
clearant state characterized by hepatitis B s-antigen negative serum with or
without sero-conversion. The siRNAs in ARC-520 intervene at the point of DNA
transcription, upstream of where nucleotide and nucleoside analogues act. In
transient and transgenic mouse models of HBV infection, a single co-injection
of Arrowhead’s DPC delivery vehicle with cholesterol-conjugated siRNA
targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins
and viral DNA with long duration of effect. In a chimpanzee chronically
infected with HBV and high viremia and antigenemia, ARC-520 induced rapid
reductions of 90-95% in HBV DNA, e-antigen, and s-antigen. Arrowhead has
completed enrollment in a phase 1 single ascending dose study in normal
volunteers, which the company expects to follow with a phase 2a study in
chronic HBV patients.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a biopharmaceutical company developing
targeted RNAi therapeutics. The company is leveraging its proprietary drug
delivery technologies to develop targeted drugs based on the RNA interference
mechanism that efficiently silence disease-causing genes. Arrowhead
technologies also enable partners to create peptide-drug conjugates that
specifically home to cell types of interest while sparing off-target tissues.
Arrowhead’s pipeline includes clinical programs in chronic hepatitis B virus
and obesity and partner-based programs in oncology.

For more information please visit http://www.arrowheadresearch.com, or follow
us on Twitter @ArrowRes. To be added to the Company's email list to receive
news directly, please send an email to ir@arrowres.com

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of
the "safe harbor" provisions of the Private Securities Litigation Reform Act
of 1995. These statements are based upon our current expectations and speak
only as of the date hereof. Our actual results may differ materially and
adversely from those expressed in any forward-looking statements as a result
of various factors and uncertainties, including our ability to finance our
operations, the future success of our scientific studies, our ability to
successfully develop drug candidates, the timing for starting and completing
clinical trials, rapid technological change in our markets, and the
enforcement of our intellectual property rights. Arrowhead Research
Corporation's most recent Annual Report on Form 10-K and subsequent Quarterly
Reports on Form 10-Q discuss some of the important risk factors that may
affect our business, results of operations and financial condition. We assume
no obligation to update or revise forward-looking statements to reflect new
events or circumstances.

Contact:

Arrowhead Research Corporation
Vince Anzalone, CFA, 626-304-3400
or
The Trout Group
Lauren Glaser, 646-378-2972
ir@arrowres.com
 
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