Arrowhead Pharmaceuticals Begins Dosing in Phase 1 Study of ARO-APOC3 for Treatment of Hypertriglyceridemia

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Arrowhead Pharmaceuticals Begins...

PASADENA, Calif.–(BUSINESS WIRE)–Mar. 11, 2019–
Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it
has dosed the first subjects in a Phase 1 clinical study of ARO-APOC3,
an RNAi-based investigational medicine targeting Apolipoprotein C-III
(apoC-III) being developed for the treatment of hypertriglyceridemia.

Bruce Given, M.D., chief operating officer and head of R&D at Arrowhead,
said: “Patients with severe hypertriglyceridemia, and particularly
patients with Familial Chylomicronemia Syndrome, or FCS, do not have
adequate treatment options. Due to its activity as a triglyceride
regulator, apoC-III has the potential to be an important therapeutic
target for cardiovascular disease. The design of the ARO-APOC3 Phase 1
study is intended to provide a readout on safety and tolerability, as
well as a robust view of the pharmacologic activity and duration of
effect. ARO-APOC3 is Arrowhead’s second cardiometabolic candidate to
enter clinical studies this year, following ARO-ANG3 for the treatment
of dyslipidemias and metabolic diseases. It also represents the fifth
clinical stage RNAi therapeutic derived from our proprietary Targeted
RNAi Molecule, or TRiMTM, platform.”

AROAPOC31001 (NCT03783377)
is a Phase 1 single and multiple dose-escalating study to evaluate the
safety, tolerability, pharmacokinetics, and pharmacodynamic effects of
ARO-APOC3 in adult healthy volunteers, hypertriglyceridemic patients,
and patients with FCS. The study is designed to enroll up to 63 subjects.

The single-ascending dose (SAD) portion of the study is designed to
include 4 cohorts of 10 adult healthy volunteers with elevated
triglycerides. Each SAD subject will receive a single-dose
administration of either placebo or ARO-APOC3 at dose levels of 25, 50,
100, or 200 mg. The multiple-dose portion is designed to include 3
cohorts of patients with severe hypertriglyceridemia and 1 cohort of
patients with FCS. The multiple-dose cohorts will receive two monthly
doses of ARO-APOC3.

ApoC-III has emerged as a therapeutic target for triglyceride reduction.
ApoC-III regulates triglyceride-rich lipoproteins (TRLs) and is a known
inhibitor of lipoprotein lipase (LPL) activity and LPL-mediated
lipolysis of TRLs. ApoC-III also delays the clearance of lipoprotein
remnants by the liver by inhibiting hepatocyte receptor-mediated uptake.
Human genetic studies indicate that people with apoC-III
loss-of-function mutations show reduced risk for cardiovascular disease,
with reductions in plasma triglycerides levels, while appearing to be
phenotypically normal.

FCS is a severe rare genetic disease, with a prevalence of 1 in
1,000,000, and is often caused by single gene mutations that lead to
extremely high triglyceride levels, typically over 900 mg/dL,
representing the top 0.1% of triglyceride values measured. Such severe
elevations lead to various serious signs and symptoms, including acute
pancreatitis, which can be fatal, chronic daily abdominal pain, type II
diabetes mellitus, hepatic steatosis, and cognitive issues. There is no
currently available therapy that can adequately treat FCS.

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,
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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
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uncertainties, including the safety and efficacy of our product
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Source: Arrowhead Pharmaceuticals, Inc.

Source: Arrowhead Pharmaceuticals, Inc.

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

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LifeSci Advisors, LLC
Brian Ritchie
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