Arrowhead Presents Data Suggesting ARC-520 Induces Therapeutic Flare in Chronic Hepatitis B

  Arrowhead Presents Data Suggesting ARC-520 Induces Therapeutic Flare in
  Chronic Hepatitis B

- Presentation at the Annual Meeting of the American Association for the Study
of Liver Diseases (AASLD) demonstrates reduction of key HBV antigens and DNA,
and evidence of immune reactivation in a chimpanzee with chronic HBV infection

AASLD Annual Meeting 2013

Business Wire

PASADENA, Calif. -- November 4, 2013

Arrowhead Research Corporation (NASDAQ:ARWR), a biopharmaceutical company
developing targeted RNAi therapeutics, today announced that it presented new
data on ARC-520, its clinical candidate for the treatment of chronic hepatitis
B virus, at the 2013 AASLD Annual Meeting. The data demonstrate that
intravenous administration of two doses (2 mg/kg, 3 mg/kg) of ARC-520 in a
chimpanzee chronically infected with HBV, resulted in substantial and
sustained reductions in HBV DNA, HBeAg, and HBsAg, which did not return to
baseline until study day 43, 43, and 71 respectively. In addition, an increase
in serum alanine transaminase (ALT) occurred 4 weeks after the last dose,
coincident with the nadir of circulating HBsAg. This is suggestive of a
therapeutic immunological flare, which is thought to be part of a cascade that
under chronic therapy may lead to HBsAg seroconversion and functional cure.
Robert E. Lanford, Ph.D., of the Texas Biomedical Research Institute where the
study was conducted, presented these data and the poster was selected as a
Presidential Poster of Distinction indicating that it was in the top 10% of
all abstracts selected for poster presentation.

“This study would have been important if ARC-520 just demonstrated safe and
effective HBsAg reduction because this is thought to be a necessary step in
achieving a functional cure,” said Dr. Lanford. “What is really exciting about
these data, however, is that we appear to have seen immune de-repression, the
next step toward HBsAg seroconversion and functional cure. The timing of the
ALT rise and associated increases in key chemokine/cytokine mRNAs suggest that
they were related to the therapy-induced reduction in circulating HBsAg and
represented an immunological event.”

The study was a proof-of-concept antiviral efficacy trial for ARC-520, which
is composed of 2 cholesterol-conjugated siRNAs and the hepatocyte-targeted
membrane-lytic Dynamic Polyconjugate (DPC) delivery vehicle. It was conducted
at the Texas Biomedical Research Institute in a single chimpanzee chronically
infected with HBV since 1979 (chimpanzee 4x0139; genotype B; viral load
~1.3x10^10 GE/ml; HBsAg 824 μg/ml). Activity was monitored using serum levels
of HBV DNA, HBeAg, and HBsAg. Safety was monitored using CBC, blood
chemistries, and serum levels of 39 cytokines and chemokines. Liver histology,
viral antigens, and host transcripts were monitored in the liver.

Arrowhead previously reported initial data through day 29 of this study. The
animal was monitored at additional time points through day 85 to assess
duration of effect for ARC-520 and other outcome measures. HBV DNA levels
dropped by 17-fold by day 4, exhibited a 36-fold decline following the second
dose, and returned to baseline by day 43. HBeAg levels declined by more than
one log by day 4 and returned to baseline by day 43. HBsAg levels declined
gradually reaching a 5.2-fold reduction on day 29 and did not return to
baseline until day 71. HBsAg is a serum lipoprotein complex and has a
significant half-life in circulation, thus declines for this marker were more
gradual but also more sustained. An increase in ALT was observed near the
HBsAg nadir.

“This is an important addition to our data set and a milestone for the
development plan of ARC-520,” said Christopher Anzalone, Ph.D., Arrowhead’s
President and CEO. “We successfully completed enrollment in a Phase 1 clinical
study in healthy volunteers with initial data indicating that ARC-520 is
generally safe and well tolerated in humans. We will be filing with Hong Kong
regulatory authorities this quarter to enable a Phase 2a study in patients
with chronic HBV infection.”

Arrowhead also recently presented a poster at the 2013 International Meeting
on Molecular Biology of Hepatitis B Viruses. The data presented indicate that
treatment with ARC-520 in combination with entecavir appears to be additive
and possibly synergistic. These results support plans to initiate a Phase 2a
study of ARC-520 in combination with entecavir, pending regulatory approval.

Copies of both poster presentations can be found on the Presentations and
Events page of the Arrowhead website at
www.arrowheadresearch.com/presentations.

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 mRNA level,
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 and deep reductions 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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