Arrowhead Pharmaceuticals Hosts R&D Day on Pipeline of RNAi Therapeutics

PASADENA, Calif.–(BUSINESS WIRE)–$arwr–Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) is hosting a Research &
Development (R&D) Day today in New York to discuss its emerging pipeline
of RNAi therapeutics that leverage the Company’s proprietary Targeted
RNAi Molecule (TRiM™) platform. In addition to senior members of the
Arrowhead team, the R&D Day includes, Ira J. Goldberg, M.D., Bronfman
Professor of Medicine, Chief of the Division of Endocrinology, Diabetes,
and Metabolism, New York University Langone School of Medicine.

Presentations will begin at 1:00 p.m. EDT. A live and archived webcast
of the event, with slides, may be accessed 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 Pharmaceuticals, said: “We have made great progress since we
unveiled our proprietary TRiM™ platform just a year ago. Our first two
candidates, ARO-AAT and ARO-HBV, have advanced into clinical studies
with speed and precision and the initial data have been very promising.
In addition, our ability to target extrahepatic tissues is expanding.
This now includes lung, tumor, and today we will show initial data
demonstrating good knockdown in multiple muscle types. With this
validation and the forthcoming capital from the ARO-HBV partnership with
Janssen, we confidently enter the next phase of rapid growth for
Arrowhead. Looking forward, we expect to accomplish the following: file
2-3 new CTAs every year; target a new cell type with the TRiM™ platform
every 18 months; and, have 10 TRiM™ enabled candidates in clinical
studies by the end of 2020.”

Select R&D Day Highlights

ARO-APOC3

ARO-APOC3 is designed to reduce production of Apolipoprotein C-III
(apoC-III), a component of triglyceride rich lipoproteins (TRLs)
including very low density lipoprotein (VLDL) and chylomicrons and is a
key regulator of triglyceride metabolism. The company believes that
knocking down the hepatic production of apoC-III may result in enhanced
triglyceride metabolism and clearance of VLDL and chylomicron remnants.
Elevated triglyceride levels are an independent risk factor for
cardiovascular disease. Severely elevated triglycerides (often over
2,000 mg/dL) in patients with familial chylomicronemia syndrome (FCS), a
rare genetic disorder, can result in potentially fatal, acute
pancreatitis. Arrowhead has conducted work in multiple preclinical
models, including in transgenic mice, cynomolgus monkeys (cynos), and
high fructose fed rhesus monkeys that suggest ARO-APOC3 strongly reduces
the liver production of apoC-III and has a desired effect on serum
triglyceride levels. The company will present additional data, including
liver biopsy measurements in cynos, in an oral presentation at the
American Heart Association (AHA) meeting on November 12, 2018. In
addition, a CTA filing is planned for late 2018 to request approval to
begin a Phase 1, single and multiple ascending dose study in heathy
volunteers and in patients with elevated triglycerides.

ARO-ANG3

ARO-ANG3 is designed to reduce production of angiopoietin-like protein 3
(ANGPTL3), a liver synthesized inhibitor of lipoprotein lipase and
endothelial lipase. ARO-ANG3 is being developed for the treatment of
dyslipidemias and metabolic diseases. ANGPTL3 inhibition has been shown
to lower serum LDL, serum and liver triglyceride and has genetic
validation as a novel target for cardiovascular disease. In multiple
animal models, ARO-ANG3 led to deep ANGPTL3 knockdown in both Western
diet or chow-fed mice and significant improvements in lipid parameters.
A CTA was recently filed to begin AROANG1001, a Phase 1 single and
multiple dose study to evaluate the safety, tolerability,
pharmacokinetics, and pharmacodynamic effect of ARO-ANG3 in adult
healthy volunteers and dyslipidemic patients. The study is designed to
enroll up to 70 subjects. Arrowhead will also present additional data at
the AHA meeting on November 12, 2018.

Targeted RNAi Molecule Platform (TRiM)

Arrowhead’s Targeted RNAi Molecule platform, or TRiM™, utilizes
ligand-mediated delivery and is designed to enable multi-tissue
targeting, while being structurally simple. TRiM™ represents an
evolution in RNAi therapeutics from biologic complexity to small
molecule precision and execution. It was designed to optimize potency,
activity, durability, and safety. Important differentiators of the TRiM™
platform include:

  • TRiM™ platform demonstrates versatility for both hepatic and
    extrahepatic targets

    • Potency, activity, durability and safety
    • Speed and high success rates
  • Hepatocyte targets

    • Expertise in RNAi chemistry and biology
    • We have yet to encounter a hepatocyte gene that we could not knock
      down effectively and with a wide therapeutic index
  • Extrahepatic targets

    • Requires all TRiM™ platform modules to be fully optimized
    • Expertise in uncovering ligand/receptor pairs
    • Expertise in ligand designs to enable maximal uptake through
      endocytosis
  • Successful extrahepatic, systemic delivery of RNAi triggers via IV and
    subcutaneous administrations in ccRCC
  • Expanding extrahepatic capabilities to now include delivery to the
    lung, tumor, and muscle tissue

ARO-ENaC Gen 1

ARO-ENaC is designed to reduce production of the epithelial sodium
channel alpha subunit (αENaC) in the airways of the lung. In cystic
fibrosis patients, increased ENaC activity contributes to airway
dehydration and reduced mucociliary transport. ENaC inhibitors promise a
genotype-agnostic therapeutic approach for potentially all CF patients,
including those with Class I mutations that produce no CFTR protein.
Inhaled small molecule inhibitors transiently improve lung mucociliary
clearance, but they are rapidly absorbed and systemic exposure results
in renal ENaC inhibition and hyperkalemia. Inhalation of aerosolized
ARO-ENaC Gen 1 selectively and durably silences ENaC mRNA expression in
the rat lung while sparing the kidney. In addition, improved mucociliary
clearance was observed in sheep two weeks after inhalation of
aerosolized ARO-ENaC Gen 1. Work on a next-generation ARO-ENaC is
focused on further increasing potency to produce in vivo clearance
increases similar to short-acting small molecule ENaC inhibitors. A CTA
is planned for ARO-ENaC in 2019. The platform may also be adapted to
additional therapeutic targets in the pulmonary epithelium, particularly
those that are currently inaccessible to traditional small molecule or
antibody approaches.

ARO-HIF2

ARO-HIF2 is designed to inhibit the production of HIF2α, which has been
linked to tumor progression and metastasis, for the treatment of clear
cell renal cell carcinoma (ccRCC). Arrowhead believes it is an
attractive target for intervention because most ccRCC tumors express a
mutant form of the Von Hippel-Landau protein that is unable to degrade
HIF-2α, leading to its accumulation during tumor hypoxia and promoting
tumor growth. ARO-HIF2 has demonstrated effective tumor delivery and
deep HIF2α mRNA knockdown in tumors. In addition, ARO-HIF2 led to
inhibition of tumor growth and improved overall survival in tumor
models. Initial rat exploratory toxicity studies predict that ARO-HIF2
may have a wide safety margin. Additional data is planned to be
presented as a late-breaking poster at the EORTC/AACR/NCI symposium
being held November 13-16, 2018. A CTA is planned for ARO-HIF2 in 2019.

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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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 likelihood and
timing of the receipt of future milestone and licensing fees, the future
success of our scientific studies, our ability to successfully develop
and commercialize 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.

Contacts

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

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