Arrowhead to Present Late-Breaking Clinical Data on ARO-AAT and ARO-HBV at AASLD Liver Meeting® 2018

Arrowhead to Present Late-Breaking...

PASADENA, Calif.–(BUSINESS WIRE)–Oct. 11, 2018–
Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) will make two
late-breaking poster presentations at The Liver Meeting® 2018, the
Annual Meeting of the American Association for the Study of Liver
Disease (AASLD) being held on November 9-13, 2018, in San Francisco. The
abstracts became available today on the Online
Planner on the AASLD website.

ARO-HBV Presentation Details

First Results with RNA interference (RNAi) in Chronic Hepatitis B
(CHB) Using ARO-HBV

Publication Number: LB-25
Session: Late-Breaking Poster Session
Session Date and Time: November 12, 2018 from 8:00 AM to 5:30 PM PT
Location: Moscone Center North/South Building, Hall C
Authors: Dr. Edward J. Gane, et al.

Abstract

Background: RNAi has shown promise as a potential component of
finite therapy for patients with chronic hepatitis B (CHB) based on its
ability to silence HBV mRNA thereby reducing all viral products, most
notably HBsAg. Clinical utility has been limited by IV delivery and/or
safety concerns. ARO-HBV is composed of two siRNAs, each directly
conjugated to N-acetyl galactosamine to drive hepatocyte delivery.
Administered subcutaneously (SQ), it is designed to silence all mRNA
from cccDNA and host integrated viral DNA, without need for additional
delivery elements.

Methods: Normal healthy volunteer (NHV) cohorts (4 active, 2
placebo) received single SQ doses of 35, 100, 200, 300 or 400 mg. CHB
cohorts 2b-5b (n=4, HBeAg pos or neg, NUC treated or not on NUCs)
received monthly doses x 3 of 100, 200, 300 or 400 mg. Cohorts of HBeAg
pos, NUC naïve and experienced CHB (cohorts 8, 9 respectively, n=4 each)
are receiving 300 mg monthly x 3. NUC untreated receive NUCs from day 1.
Results reported are from 28 days after 3rd dose (day 85) when available
or most recent.

Results: No serious AEs or dropouts in NHVs or CHBs have been
reported. AEs were mild and similar in occurrence for active or placebo.
Injection site AEs (all mild) occur in ~11% of injections. For cohorts
2b-5b (n=16 active), 14 were BLQ for HBV DNA and 13 were HBeAg negative
at baseline; 14 on chronic NUCs. In CHB, mean (max) log10 reductions in
HBsAg were: 100 mg 2.0 (4.0) through Day 85, 200 mg 1.6 (2.2) through
Day 85, 300 mg 1.5 (2.2) through Day 85 and 400 mg 1.7 (3.0) through day
71 in cohorts 2b-5b and 1.5 (3.0) in cohort 8 through day 43 and 1.0
(1.3) through day 15 in cohort 9. All patients reaching day 85 have >
1.0 log10 reduction in HBsAg with additional HBsAg decreases observed
after the second and third doses. Of these 24 CHB, 21 had HBsAg >100
IU/ml at baseline and currently 17 have achieved HBsAg <100, 7 ≤10, 4
≤1. In CHB with other viral parameters above LLOQ at baseline, all have
improved following ARO-HBV, including reduction to BLQ in: HBV DNA (2 of
7), HBV RNA (8 of 14), HBeAg (0 of 11) and HBcrAg (3 of 15).

Conclusions: ARO-HBV has been well tolerated in NHVs and CHB.
~11% of SQ injections were associated with mild injection site AEs.
Monthly RNAi with ARO-HBV effectively reduces all measurable viral
products, including HBsAg. ARO-HBV has characteristics desirable for
RNAi to become a cornerstone therapy in finite regimens aimed at HBsAg
clearance in CHB.

ARO-AAT Presentation Details

A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the
Safety, Tolerability, Pharmacokinetics and Effect of ARO-AAT on Serum
Alpha-1 Antitrypsin levels in Normal Adult Volunteers

Publication Number: LB-9
Session: Late-Breaking Poster Session
Session Date and Time: November 12, 2018 from 8:00 AM to 5:30 PM PT
Location: Moscone Center North/South Building, Hall C
Authors: Dr. Christian Schwabe, et al.

Abstract

Background: Alpha-1 antitrypsin deficiency (AATD) is an autosomal
co-dominant genetic disorder causing liver disease in children and
adults. Alpha-1 antitrypsin (AAT) is a glycoprotein produced primarily
in hepatocytes. The PiZ mutation causes improper AAT folding and
impaired secretion by hepatocytes leading to accumulation in the liver
of AAT aggregates known as globules. Accumulated globules can lead to a
recurrent cycle of hepatic injury, fibrosis, cirrhosis and
hepatocellular carcinoma. ARO-AAT is a hepatocyte targeted RNAi
therapeutic designed to silence production of Z-AAT protein with the
intent of reducing liver globules. In a mouse model, reduced liver Z-AAT
synthesis correlated to reduced serum AAT and reduced Z-AAT globules
prevented progression and development of AATD-associated liver disease.

Methods: 45 healthy volunteers (age 18-52) received escalating
single or multiple doses of ARO-AAT by subcutaneous injection. Subjects
were randomized (4 placebo:4 active) to receive single 35 mg doses of
ARO-AAT or placebo. Multi-dose cohorts (4 placebo:4 active) received
three doses every 28 days at doses of 100, 200 or 300 mg. In parallel,
open label cohorts enrolled 4 subjects each receiving a single dose of
ARO-AAT at 100, 200 and 300 mg to assess single dose duration of
response. Assessments included safety (including pulmonary function
tests), tolerability, pharmacokinetics, and pharmacodynamics. Subjects
were evaluated through at least Day 29 (35 mg single dose cohort) or Day
113 (open label and multi-dose cohorts) or until AAT levels returned to
20% below baseline or above 90 mg/dL.

Results: No deaths, SAEs or severe AEs have been reported. The
most common AEs were headache (22%) and rhinorrhea (13%). Single dose
serum AAT mean nadir reductions from baseline of 79%, 87%, >91% and >91%
were reported at 35, 100, 200 and 300 mg respectively. Multi-dose mean
nadir serum AAT reductions were >91% at all dose levels with most
subjects BLQ. Maximum AAT reduction across all cohorts was >94%. A
greater than 90% reduction was sustained for at least 8 weeks following
the last dose in the lowest multi-dose cohort (100 mg), the only cohort
with data of this duration.

Conclusions: ARO-AAT has been well tolerated at doses as high as
300 mg given three times every 28 days. Maximum nadir reduction of >94%
from baseline indicates potent siRNA inhibition of hepatic AAT
synthesis. Based on duration of response, quarterly or less frequent
dosing appears feasible.

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

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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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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candidates, the duration and impact of regulatory delays in our clinical
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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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Source: Arrowhead Pharmaceuticals, Inc.

View source version on businesswire.com: https://www.businesswire.com/news/home/20181011005617/en/

Source: Arrowhead Pharmaceuticals, Inc.

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