Arrowhead Pharmaceuticals Presents New Preclinical Data on ARO-ENaC for Treatment of Cystic Fibrosis

Home/Newsroom/

Arrowhead Pharmaceuticals Presents...

PASADENA, Calif.–(BUSINESS WIRE)–May 21, 2018–
Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced the
presentation of new preclinical data on ARO-ENaC, formerly referred to
as ARO-Lung1, for the treatment of cystic fibrosis (CF), at the American
Thoracic Society (ATS) 2018 International Conference in San Diego,
CA. ARO-ENaC is the first product candidate to leverage the Targeted
RNAi Molecule (TRiM™) platform targeting the pulmonary epithelium to
address diseases of the lung.

ARO-ENaC is an inhaled RNA interference (RNAi) therapeutic targeting the
epithelial sodium channel alpha subunit (αENaC) for the treatment of CF,
a rare disease caused by a genetic mutation that leads to mucus buildup
in the lungs and pancreas. CF patients can have difficulty breathing and
experience frequent and persistent lung infections. Increased ENaC
activity contributes to drying mucus in the airway and a reduced ability
of the lung to clear toxins and infectious agents. Inheritance of poorly
functioning ENaC genes by CF patients leads to milder lung disease.

Researchers have been interested in developing therapeutics that
decrease ENaC activity in CF patients. However, the development of
inhaled small molecule inhibitors has been limited by their short
duration of action and unwanted effects resulting from ENaC inhibition
in the kidney. ARO-ENaC is designed specifically to address those
deficiencies by selectively reducing ENaC in the lung, while sparing the
kidney, with a long duration of effect.

Christopher Anzalone, Ph.D., president and chief executive officer at
Arrowhead, said, “The Targeted RNAi Molecule, or TRiM™, platform has
several important advantages over the prior generation and competing
technologies, including the ability to target tissues and diseases
outside of the liver. ENaC is a genetically and biologically validated
target for cystic fibrosis with a profile that we believe is well-suited
for an RNAi-based intervention. We view ARO-ENaC as an important proof
of concept for future TRiM™ enabled candidates targeting additional
pulmonary diseases.”

A poster titled, “Targeting αENaC with an epithelial RNAi trigger
delivery platform for the treatment of cystic fibrosis,” was presented
by Erik Bush, Ph.D., Arrowhead’s director of extra-hepatic targeting.
Dr. Bush’s presentation contained new preclinical data on ARO-ENaC and
advancements being made with the TRiM™ platform. The data presented
included the following:

  • Integrin αvβ6 receptor ligands improve endocytosis of RNAi triggers in
    cultured epithelial cells
  • Conjugates employing targeting ligands to the integrin αvβ6 receptor
    improve functional delivery of an αENaC RNAi trigger to the pulmonary
    epithelium after inhalation, producing deeper and more consistent
    reduction of whole lung αENaC mRNA at lower doses
  • Loss of airway epithelial αENaC protein expression is observed at
    exposures that produce approximately 50% reduction in whole lung αENaC
    mRNA, with remaining protein expressed in alveolar epithelium
  • Reduction of lung αENaC mRNA expression is durable, maintaining
    greater than the target level of 50% knockdown at 3 weeks post-dose
    and requiring 6-7 weeks for recovery to baseline expression
  • Aerosol inhalation improves delivery efficiency approximately tenfold
    over intratracheal administration
  • Conjugates were well-tolerated with no observed changes in renal αENaC
    mRNA expression
  • The ability of the TRiM™ platform to facilitate functional delivery of
    RNAi triggers to the lung suggests that additional therapeutic targets
    in the pulmonary epithelium could be considered, particularly those
    that are currently inaccessible to traditional small molecule or
    antibody approaches

A copy of presentation materials may be accessed on the Events
and Presentations page under the Investors section of the Arrowhead
website.

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.
To be added to the Company’s email list and receive news directly,
please visit http://ir.arrowheadpharma.com/email-alerts.

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.

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
212-915-2578
britchie@lifesciadvisors.com
www.lifesciadvisors.com