Arrowhead Presents Data Showing Robust Sustained Anti-viral Effects with ARC-520 in Hepatitis B Infected Chimpanzees

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Arrowhead Presents Data Showing...

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical

company developing targeted RNAi therapeutics, presents data at the

AASLD Liver Meeting 2015® in an oral presentation and

a poster showing that ARC-520, its drug candidate against chronic

hepatitis B infection (HBV), leads to robust, sustained anti-viral

effects in chimpanzees with chronic HBV. Arrowhead also describes an

important new discovery that HBV DNA integrated into the host genome is

likely an important source of HBV surface antigen (HBsAg) production,

particularly in chimps that are negative for hepatitis B e-antigen

(HBeAg). The company plans to present additional data from this study at

the 2015 Hep Dart conference in December demonstrating that two of four

HBeAg-positive chimps exhibited signs of immune reactivation, which is

believed to be a necessary step toward achieving a functional cure of

HBV.

“We believe that these data change current HBV biology dogma,” said

Bruce D. Given, M.D., Arrowhead’s chief operating officer. “We have

gained insights about the HBV life cycle during the chimpanzee study,

and this has informed our clinical program for ARC-520. In addition, it

has enabled us to expand our HBV portfolio to include ARC-521, our new

drug candidate that may be highly active against HBsAg in patient

populations with higher relative levels of integrated DNA.”

ARC-520 led to a dramatic drop in circulating HBsAg, with the degree of

HBsAg reduction correlating with HBeAg status. HBeAg-positive and

-negative chimps demonstrated HBsAg reductions of 1.5 – 2.7 log (96.8% –

99.8%) and 0.5 – 0.9 log (68.4% – 87.4%), respectively, with an

intermediate response in a chimp transitioning from HBeAg positive to

negative. In addition, one chimp seroconverted for HBeAg during ARC-520

therapy and had a sustained virologic response with respect to HBeAg,

HBV DNA, and HBsAg. This persisted off therapy and through at least 32

weeks after ARC-520 and NUC therapy was removed, which was the last

time-point observed. A second chimp demonstrated effects consistent with

immunologic reactivation.

In the study, Arrowhead found that the predominant form of liver HBV DNA

differed in HBeAg-negative versus HBeAg-positive chimps. Most HBV DNA in

HBeAg-positive chimps was cccDNA, while less than 5% of HBV DNA in

HBeAg-negative chimps was cccDNA. In addition, Arrowhead found that the

HBV RNA profiles in HBeAg-negative chimps were consistent with

transcripts arising from integrated DNA. These data and others, strongly

suggest that integrated DNA is likely an important source of HBsAg

production in HBeAg-negative chimps.

Direct confirmatory data was obtained by treating HBeAg negative chimps

with a siRNA designed to target transcripts originating from integrated

HBV DNA. Up to an additional 2 logs (99%) of HBsAg knockdown was

achieved, resulting in overall relative knockdown levels that are

similar to those observed using ARC-520 in HBeAg-positive chimps.

Arrowhead has incorporated one of these RNAi triggers and one targeting

predominantly cccDNA derived transcripts into a new complementary drug

candidate, ARC-521, that is planned to be in clinical trials in 2016.

The study presented at AASLD included 9 chimpanzees chronically infected

with HBV. At the beginning of the study four were HBeAg-positive, four

were HBeAg-negative, and one was in the process of transitioning from

HBeAg-positive to HBeAg-negative. To reduce viral replication prior to

treatment with ARC-520, chimps were treated for 8-24 weeks with

entecavir (ETV) and in one case with ETV plus tenofovir (TDF). Following

the NUC lead-in period, animals were administered ARC-520 intravenously

at 4-week intervals (q4w). Dose levels were 2, 3, or 4 mg/kg ARC-520,

along with maintenance doses of ETV or ETV and TDF. The response to NUCs

during the lead-in period was similar to therapy in humans with deep

decreases in serum HBV DNA but minimal effects on HBsAg levels.

Copies of presentation materials can be accessed by visiting the Events

section of the company’s website at http://ir.arrowheadresearch.com/events.cfm.

About ARC-520

Arrowhead’s RNAi-based candidate ARC-520 is being investigated in the

treatment of chronic HBV infection. The small interfering RNAs (siRNAs)

in ARC-520 intervene at the mRNA level, upstream of the reverse

transcription process where current standard of care nucleotide and

nucleoside analogues act. Arrowhead is investigating ARC-520

specifically to determine if it can be used to achieve a functional

cure, which is an immune clearant state characterized by hepatitis B

s-antigen negative serum with or without seroconversion. Arrowhead is

conducting Phase 2b multiple dose and combination studies in chronic HBV

patients. Approximately 350-400 million people worldwide are chronically

infected with the hepatitis B virus, which can lead to cirrhosis of the

liver and is responsible for 80% of primary liver cancers globally.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a biopharmaceutical company developing

targeted RNAi therapeutics. The company is leveraging its proprietary

Dynamic Polyconjugate™ delivery platform to develop targeted

drugs based on the RNA interference mechanism that efficiently silences

disease-causing genes. Arrowhead’s pipeline includes ARC-520 and ARC-521

for chronic hepatitis B virus, ARC-AAT for liver disease associated with

alpha-1 antitrypsin deficiency, ARC-F12 for hereditary angioedema and

thromboembolic diseases, and ARC-HIF2 for renal cell carcinoma.

For more information please visit http://www.arrowheadresearch.com,

or follow us on Twitter @ArrowRes.

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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.

DYNAMIC POLYCONJUGATES is a trademark of Arrowhead Research

Corporation.

Source: Arrowhead Research Corporation

Arrowhead Research Corporation
Vince Anzalone, CFA, 626-304-3400
ir@arrowres.com
or
Investor

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Source: Arrowhead Research Corporation

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