Arrowhead Pharmaceuticals Presents New Data on ARC-AAT

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Arrowhead Pharmaceuticals Presents...

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) delivered a poster

presentation with Phase 1 clinical data and an oral presentation with

preclinical data on ARC-AAT, its investigational medicine for the

treatment of liver disease associated with alpha-1 antitrypsin

deficiency (AATD), at The Liver Meeting® 2016, the Annual Meeting of the

American Association for the Study of Liver Disease (AASLD), in Boston.

The data indicate that in a first-in-human clinical study, ARC-AAT was

well tolerated and induced deep and durable reduction of the target AAT

protein. The preclinical data suggest that treatment with ARC-AAT over

time may improve liver health and prevent further damage.

Bruce Given, M.D., chief operating officer of Arrowhead Pharmaceuticals,

said: “We showed some exciting data today indicating that ARC-AAT, both

clinically and in a preclinical model, is doing precisely what it is

designed to do. In these studies, ARC-AAT led to deep, durable, and

dose-dependent silencing of the liver production of the AAT protein.

Accumulation of the mutant Z-AAT is believed to be the cause of

progressive liver disease in patients with AATD, and reducing the

production is important as it is expected to halt the progression of

liver disease. Specifically, in the clinical study ARC-AAT led to a

maximum reduction of up to 90% in the highest dose group, which we

believe to be near full suppression of the liver production of the

protein, and a mean maximum reduction of 88%. We are also pleased that

in the clinical study ARC-AAT was well tolerated at all dose levels

studied (0.3 – 8 mg/kg), which is consistent with the tolerability

profile of our other clinical programs that use the same DPCivTM

(EX1) delivery vehicle.”

The poster titled, “RNA interference (RNAi) with ARC-AAT provides

deep and prolonged knockdown of alpha-1 antitrypsin levels in healthy

volunteers,” publication LB-24 in the late-breaking poster session,

describes data from a Phase 1, multi-center, randomized,

placebo-controlled, double-blind, single dose-escalation first-in-human

study to evaluate the safety, tolerability, pharmacokinetics of ARC-AAT

and the effect on circulating alpha-1 antitrypsin (AAT) levels. Key

findings from the study include the following:

  • Dose-dependent reductions in serum AAT of up to 90% were observed

  • Duration of effect indicates that monthly, or less frequent, dosing is

    likely

  • Pharmacokinetic (PK) parameters were linear across dose levels with a

    constant half-life

  • There have been no drop outs due to adverse events (AE), no clinically

    significant changes in ECGs, DLCO or FEV1, and one serious adverse

    event (SAE) in a placebo subject

  • No clinically significant transaminase (ALT, AST) elevations were

    reported

  • The most frequently reported ARC-AAT related AEs were headache, nausea

    and rigor (each, 3 events in 36 [8%] subjects)

The oral presentation titled, “RNA interference therapeutic ARC-AAT

prevents production of Z-alpha1 antitrypsin polymers and reverses liver

disease phenotype in PiZ mouse model,” publication 124 in the

session Parallel 19: Pediatric and Metabolic Liver Diseases: Basic and

Translational, describes data from a 33-week study of ARC-AAT in the PiZ

mouse model. Key findings from the study include the following:

  • Cleared Z-hAAT protein from the cytoplasm and reduced by &#62 90% in serum

  • Prevented and reversed polymer accumulation, with Z-hAAT monomer

    reduced by 87% and polymer by 42% at week 33

  • Halted accumulation of Z-hAAT globules in the liver, with 61% less in

    ARC-AAT treated compared to saline controls and 24% less than at

    baseline

  • Improved liver health and prevented further damage based on

    histopathology improvements compared to baseline and saline controls

  • Prevented liver inflammation with fewer inflammatory foci and reduced

    total area of inflammation

  • Prevented liver tumors

  • Normalized gene expression associated with liver disease

A copy of presentation materials will be made available on the Events

and Presentations page under the Investors section of the Arrowhead

website.

About ARC-AAT

Arrowhead’s ARC-AAT is being investigated for the treatment of liver

disease associated with alpha-1 antitrypsin deficiency (AATD), a rare

genetic disease that severely damages the liver and lungs of affected

individuals. The mean estimated prevalence of AATD in the U.S. is 1 per

3000-5000, or approximately 100,000 patients. AATD is also an important

cause of pediatric liver disease with an estimated prevalence in

children of approximately 20,000 patients, and 50-80% likely to manifest

liver disease during childhood. It is a rare disease that is frequently

misdiagnosed or undiagnosed. ARC-AAT employs a novel unlocked nucleobase

analog (UNA) containing RNAi trigger molecule designed for systemic

delivery using the Dynamic Polyconjugate™ delivery system.

ARC-AAT is highly effective at knocking down the alpha-1 antitrypsin

(AAT) gene transcript and reducing the hepatic production of the mutant

AAT (Z-AAT) protein in animal studies. Reduction of liver production of

the inflammatory Z-AAT protein, which is believed to be the cause of

progressive liver disease in AATD patients, is important as it is

expected to halt the progression of liver disease. ARC-AAT was granted

orphan drug designation in both the United States and in Europe, the

latter being held on Arrowhead’s behalf by a local EU representative

Pharma Gateway AB. Arrowhead is conducting a Phase 1 clinical study of

ARC-AAT, with part A in healthy volunteers (now complete) and part B in

AATD patients, and a Phase 2 multiple dose study in AATD patients.

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. The company’s pipeline includes ARC-520 and ARC-521 for

chronic hepatitis B virus infection, ARC-AAT for liver disease

associated with alpha-1 antitrypsin deficiency, ARC-F12 for hereditary

angioedema and thromboembolic disorders, ARC-LPA for cardiovascular

disease, and ARC-HIF2 for renal cell carcinoma.

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

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and subsequent Quarterly Reports on Form 10-Q discuss some of the

important risk factors that may affect our business, results of

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revise forward-looking statements to reflect new events or circumstances.

DYNAMIC POLYCONJUGATES is a trademark of Arrowhead

Pharmaceuticals, Inc.

Source: Arrowhead Pharmaceuticals, Inc.

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

Relations:
The Trout Group
Chad Rubin
646-378-2947
ir@arrowheadpharma.com
or
Media:
Russo

Partners
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212-845-4272
matt.middleman@russopartnersllc.com

Source: Arrowhead Pharmaceuticals, Inc.

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