Arrowhead Data Reveal Important Considerations for Future Hepatitis B Treatment

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Arrowhead Data Reveal Important...

– Results May Guide New Clinical Approaches, Science Translational

Medicine Study Shows –

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced results

from studies of ARC-520, a prior-generation RNAi therapeutic candidate

against chronic hepatitis B virus (HBV) infection, in a Phase 2 clinical

study in HBV patients and a complementary study in chimpanzees

chronically infected with HBV. These studies demonstrated that HBV DNA

integrated into the host genome is an under-appreciated source of HBV

surface antigen (HBsAg), a key protein implicated in maintaining chronic

HBV infection.

In many patients, integrated HBV DNA appeared to be the dominant source

of HBsAg production. The findings expand the understanding of HBV

biology and host interactions, and could have important implications for

future trial design and endpoint expectations for new therapies

developed to cure chronic HBV. These data from study, “RNAi-based

treatment of chronically infected patients and chimpanzees implicates

integrated hepatitis B virus DNA as a source of HBsAg” were published in Science

Translational Medicine.

Bruce D. Given, M.D., chief operating officer and head of R&D for

Arrowhead Pharmaceuticals, said: “Our experience from Arrowhead’s

multiple clinical studies of our prior therapeutic candidates ARC-520

and ARC-521, and the extensive non-clinical research we completed, have

provided us with invaluable insights that guide the development path of

follow-on candidate ARO-HBV, a new therapy for patients with chronic HBV

that utilizes the company’s next generation Targeted RNAi Molecule

(TRiM™) platform. We think long-term immune control of HBV will require

reduction of HBsAg from both integrated DNA and cccDNA, which ARO-HBV is

designed to do. Importantly, the findings described in the Science

Translational Medicine paper extend beyond HBsAg in showing reductions

in other viral antigens and viral DNA. The ARC-520 and ARC-521 data

suggest that an RNAi-based approach, like ARO-HBV, could serve as a

cornerstone therapy for combinations intended to cure chronic HBV

because it can act as a direct anti-viral against all HBV viral products

and has the potential to synergize with other agents.”

The paper entitled, “RNAi-based treatment of chronically infected

patients and chimpanzees implicates integrated hepatitis B virus DNA as

a source of HBsAg,” by Christine I. Wooddell and Man-Fung Yuen et al,

was made available online ahead of print in the journal Science

Translational Medicine (27 September 2017).

In the publication, several independent lines of evidence demonstrate

that HBsAg is expressed not only from the episomal covalently closed

circular DNA (cccDNA) minichromosome, but also from transcripts arising

from HBV DNA integrated into the host genome. The latter was a large

source of HBsAg production in HBeAg negative chimpanzees and presumed,

by extension, in HBeAg negative and NUC experienced patients.

“This is an important finding with wide-reaching implications for the

field because production of viral proteins was previously thought to

depend only on transcription of viral cccDNA. We now understand that

integrated HBV DNA is a means of producing circulating HBsAg that is not

dependent on viral replication, which may contribute to sustained

suppression of the immune system and allow for continued virion

production,” commented Christine I. Wooddell, Ph.D., lead study author.

“Just a few cccDNA-containing cells able to escape immune surveillance

can maintain chronic infection. Therefore, only complete immune control

of HBsAg can be expected to prevent reinfection off therapy and result

in a functional cure.”

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable

diseases by silencing the genes that cause them. Using a broad portfolio

of RNA chemistries and efficient modes of delivery, Arrowhead therapies

trigger the RNA interference mechanism to induce rapid, deep, and

durable knockdown of target genes. RNA interference, or RNAi, is a

mechanism present in living cells that inhibits the expression of a

specific gene, thereby affecting the production of a specific protein.

Arrowhead’s RNAi-based therapeutics leverage this natural pathway of

gene silencing.

For more information, please visit www.arrowheadpharma.com,

or follow us on Twitter @ArrowheadPharma.

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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 the safety and efficacy of our product

candidates, the duration and impact of regulatory delays in our clinical

programs, 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. Our 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.

Source: Arrowhead Pharmaceuticals, Inc.

Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
626-304-3400
ir@arrowheadpharma.com
or
Investors

and Media:
LifeSci Advisors, LLC
Brian Ritchie
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www.lifesciadvisors.com

Source: Arrowhead Pharmaceuticals, Inc.

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