Arrowhead Late-Breaking Clinical Data Shows that ARC-520 Can Produce Deep and Durable Reductions of Hepatitis B Viral Antigens and DNA

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Arrowhead Late-Breaking Clinical...

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical

company developing targeted RNAi therapeutics, presented data from a

Phase 2a clinical study at The AASLD Liver Meeting 2015®

demonstrating that ARC-520, its lead drug candidate against chronic

hepatitis B infection (HBV), effectively reduced HBV viral antigens

derived from cccDNA. HBV surface antigen (HBsAg) was reduced

substantially with a maximum reduction of 1.9 logs (99%) and a mean

maximum reduction of 1.5 logs (96.8%) in treatment naïve e-antigen

(HBeAg)-positive patients. This direct antiviral effect was still

evident 57 days after a single dose. These data strongly support

advancement of ARC-520, and Arrowhead has initiated multiple studies

aimed at producing a functional cure of HBV.

Christopher Anzalone, Ph.D., Arrowhead’s president and chief executive

officer said, “At AASLD we presented data from our clinical program and

from a nonclinical study in chimpanzees. Both of these studies show that

ARC-520 can produce deep and durable knockdown of HBV viral antigens.

These data give us additional confidence in the program as we move

forward with multiple-dose and combination studies of ARC-520, that we

hope will lead to host immune reconstitution, HBsAg seroclearance, and

functional cure.”

Man-Fung Yuen, M.D., Ph.D., chair of gastroenterology and hepatology,

The University of Hong Kong, and deputy chief of service, Queen Mary

Hospital department of medicine, Hong Kong, and a principal investigator

for Arrowhead’s Phase 2a clinical study, delivered a late-breaking

poster presentation titled, “ARC-520 produces deep and durable

knockdown of viral antigens and DNA in a phase II study in patients with

chronic hepatitis B“.

In this presentation, Dr. Yuen and co-authors show that in the

Heparc-2001 clinical study, ARC-520 in combination with entecavir

achieved maximum reductions of HBsAg, HBV DNA, HBeAg, and core-related

antigen (HBcrAg) of 1.9 logs (99%), 4.3 logs (99.995%), 1.7 logs (98%),

and 1.2 logs (93.7%), respectively.

HBeAg-positive, treatment naïve patients achieved consistent reductions

in HBsAg with a mean maximal reduction of 1.5 logs (96.8%). ARC-520

caused a direct antiviral effect after a single dose that was still

evident after 57 days, which was the last time-point available.

Consistent with findings from Arrowhead’s chimpanzee study, also

presented at AASLD, variations in viral antigen reduction indicated that

patients previously treated with chronic entecavir and patients that

were treatment-naive and negative for HBeAg likely had lower levels of

cccDNA derived mRNA transcripts. As such, HBeAg-positive treatment naïve

patients experienced a greater relative reduction in HBsAg than patients

that were HBeAg-negative or treatment experienced. One transitional

patient in cohort 7 was HBeAg-positive at baseline and became

HBeAg-negative at days 3 to 43. This patient experienced an intermediate

response initially, however HBsAg continued to trend downward through

day 57, the last time-point available.

In the clinical study, 58 patients with chronic HBV received doses of

1mg/kg – 4 mg/kg of ARC-520 in 7 cohorts. The cohorts varied by ARC-520

dose, HBeAg status, and prior NUC treatment status. The primary

objective of the study was to measure the depth and duration of HBsAg

reduction in response to a single dose or two doses (cohort 6) of

ARC-520 in combination with entecavir. Arrowhead also assessed safety

and tolerability and additional secondary and exploratory endpoints.

ARC-520 was well tolerated with no serious adverse events (AE), no dose

limiting toxicities, no discontinuations due to medication AEs, and a

modest occurrence rate (23%) of AEs that were all deemed unrelated to

study drug by the principal investigator. No AE occurred more than once.

There were no AEs amongst 10 patients receiving placebo. There was a low

occurrence rate of abnormal laboratory tests, with no observed

relationship to timing or dose.

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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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

Relations:
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Chad Rubin
646-378-2947
ir@arrowres.com
or
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Source: Arrowhead Research Corporation

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