Arrowhead Presents New Clinical Data on ARO-AAT at Alpha-1 National Education Conference

Home/Newsroom/

Arrowhead Presents New Clinical...

PASADENA, Calif.–(BUSINESS WIRE)–Jun. 29, 2018–
Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today will present
preclinical and initial clinical data on ARO-AAT, the company’s second
generation subcutaneously administered RNA interference (RNAi)
therapeutic being developed as a treatment for a rare genetic liver
disease associated with alpha-1 antitrypsin (AAT) deficiency, at the
Alpha-1 National Education Conference in San Francisco. These results
represent the first human data derived from Arrowhead’s pipeline of RNAi
therapeutics that leverage its proprietary Targeted RNAi Molecules
(TRiM™) platform.

Key new clinical data to be presented include the following:

  • In the AROAAT1001 Phase 1 clinical study, a single, open-label dose of
    100 mg of ARO-AAT in four subjects achieved 93% maximum serum AAT
    knockdown and 87% mean maximum serum AAT knockdown. At 8 weeks
    post-dose, mean serum AAT knockdown remained at 83%.
  • The single 100 mg dose of ARO-AAT equates to an average dose of 1.4
    mg/kg (range 1.0-1.6 mg/kg) in the subjects studied, who had an
    average weight of 72.9 kg (range 61.8-98.9 kg)
  • ARO-AAT appeared to be generally well-tolerated and as of the data
    cutoff of June 11, 2018, the following safety measures were observed
    in 40 subjects (24 received ARO-
    AAT and 16 received placebo):

    • No serious or severe adverse events (AEs)
    • Most AEs reported were mild (one moderate gastroenteritis)
    • 2 cases of injection site erythema at 100 mg after 1st dose

      • Both were classified as mild and resolved within 48 hours
    • No clinically meaningful adverse changes in BUN, creatinine, ALT,
      AST or total bilirubin
    • No dose-related pattern of adverse laboratory changes seen

Preclinical data previously presented showed:

  • Treatment with ARO-AAT for 8 weeks led to reductions in Z-AAT monomer
    and polymer content, and prevention of globule accumulation in the
    livers of young PiZ mice
  • Two doses of 3 mg/kg of ARO-AAT led to 92% maximum serum AAT knockdown
    that was sustained for over 7 weeks following the second dose in
    nonhuman primates

A copy of the presentation slides can be accessed now on the Events
and Presentations page under the Investors section of the Arrowhead
website.

Chris Anzalone, Ph.D., president and chief executive officer of
Arrowhead, said, “In our presentation today at the Alpha-1 National
Education Conference, we will present initial human clinical data from a
cohort of healthy volunteers in a Phase 1 study of ARO-AAT, the first
clinical candidate to leverage Arrowhead’s proprietary Targeted RNAi
Molecule, or TRiM™, platform. The 100 mg open-label, single-dose cohort
showed strong activity with a maximum serum AAT reduction of 93%. Based
on our experience in primates and prior human clinical studies, we
believe this knockdown level represents near full suppression of the
liver production of AAT. In addition, the duration of effect we’re
seeing should enable monthly or less frequent dosing. We are excited by
these results and would like to thank the Alpha-1 Foundation for
providing us with a forum to discuss the development of ARO-AAT with the
Alpha-1 community.”

Henry R. Moehring, president and chief executive officer of the Alpha-1
Foundation, said, “We know the Arrowhead team well and thank them on
behalf of the Alpha-1 community for their dedication to developing a
treatment for the liver disease associated with alpha-1 antitrypsin
deficiency. We view the partnership between Arrowhead, the Alpha-1
Foundation, and our venture philanthropy subsidiary, The Alpha-1
Project, as a great example of how industry and disease foundations can
work together on new innovative treatments that benefit patients with
rare diseases.”

Arrowhead’s presentation is part of a session titled, “Driving New
Therapies and Tools in Alpha-1 – Presentation & Panel Discussion,”
scheduled for 3:45-5:20 p.m. PDT. The Alpha-1 National Conference is the
largest annual gathering of Alphas, their families, leading healthcare
professionals, and industry in the world. It is a three day event with
educational programs given by national experts and leaders in the
Alpha-1 field. Additional information about the conference can be found
on the Alpha-1
Foundation website.

AROAAT1001 (NCT03362242)
is a Phase 1 single- and multiple-ascending dose study to evaluate the
safety, tolerability, pharmacokinetics, and effect of ARO-AAT on serum
alpha-1 antitrypsin levels in healthy adult volunteers. The study
includes 7 cohorts in which 16 subjects receive placebo and 28 subjects
receive single or multiple doses of ARO-AAT at doses of 35, 100, 200, or
300 mg. Additional cohorts were planned at a dose of 400 mg, but were
deemed unnecessary based on the observed activity at lower doses.

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