Arrowhead Presents Data on ARC-520 and ARC-AAT at AASLD The Liver Meeting® 2014
– ARC-520 shows statistically significant reduction in HBsAg through day
43 after a single injection (p < 0.05)
– Repeat dosing of ARC-AAT in primates shows reduction of approximately
90% of serum alpha 1 antitrypsin (AAT) with long duration of effect
suggesting that monthly or less frequent dosing may be sufficient for
sustained suppression of hepatic AAT production
– ARC-AAT abstract highlighted in the AASLD President’s Press Conference
as a promising new treatment
– Arrowhead will host an investor event and presentation to discuss
results that will be webcast at 8:00 p.m. EST
PASADENA, Calif.–(BUSINESS WIRE)–
Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical
company developing targeted RNAi therapeutics, today announced that
initial data from the ongoing Phase 2a study of ARC-520, its RNAi
therapeutic candidate for the treatment of chronic hepatitis B (HBV)
infection, was presented today in the late-breaking poster session at
the 2014 American Association for the Study of Liver Diseases (AASLD)
Liver Meeting in Boston. Arrowhead also delivered a plenary presentation
with new preclinical efficacy data on ARC-AAT, its RNAi therapeutic
candidate for the treatment of liver disease associated with Alpha-1
antitrypsin deficiency.
The Company will host an investor event and presentation to discuss
these results that will be webcast tonight at 8:00 p.m. EST. Investors
may access the webcast and presentation slides on the Events page of the
Company’s website at http://ir.arrowheadresearch.com/events.cfm.
An audio only version of the live webcast may also be accessed by
calling 844-825-4406 toll-free from the U.S., or 315-625-3230 for
international callers, using conference ID 31449966. An archive of the
call will be available for seven days and may be accessed by calling
855-859-2056 or 404-537-3406. Copies of the AASLD poster and plenary
presentation will also be available to view on the Events page of the
Company’s website.
“We presented some important advancements today for both ARC-520 and
ARC-AAT,” said Christopher Anzalone, Ph.D., Arrowhead’s President and
Chief Executive Officer. “These programs and our expanding pipeline of
RNAi therapeutics continue to generate exciting data that further
validate the utility of the DPC delivery system. We have seen clear
activity across multiple preclinical models and are now seeing activity
in humans. We are still dose escalating in the ARC-520 Phase 2a, where
dosing is complete in the 3 mg/kg cohort and screening has begun for 4
mg/kg. We believe that the initial data from the first two dose cohorts
as well as safety data from the Phase 1 volunteer study are encouraging
and support advancement of the program into multi-dose Phase 2b studies.
We are currently preparing regulatory filings for the ARC-520 Phase 2b
and the ARC-AAT Phase 1, both of which we expect to be filed this
quarter. We intend to initiate those studies soon after receiving
regulatory permission to begin.”
ARC-520 Data
In a Late-Breaking Poster titled, “Phase II, dose ranging study of
ARC-520, a siRNA-based therapeutic, in patients with chronic hepatitis B
virus infection,” interim data on ARC-520 was presented by Man-Fung
Yuen, M.D., Ph.D., Chair of Gastroenterology and Hepatology, and Li Shu
Fan Medical Foundation Professor in Medicine, The University of Hong
Kong, and a principal investigator for the study. The poster included
up-to-date safety data on ARC-520 from this study, an ongoing Phase 2a
multicenter, randomized, double-blind, placebo-controlled,
dose-escalation study, as well as a recently completed Phase 1 normal
volunteer study.
The nine dose group, Phase 1, normal volunteer trial was designed to
characterize the safety profile of ARC-520 across a range of doses and
evaluate pharmacokinetics. It was a single-center, randomized,
double-blind, placebo-controlled, single dose-escalation, first-in-human
study of ARC-520 administered intravenously to healthy adult volunteers
for which partial data has been previously reported. All subjects
received either placebo or ARC-520 in doses ranging from 0.01 mg/kg to
4.0 mg/kg. The study successfully enrolled all 54 subjects (36 received
ARC-520, 18 placebo). The Phase 2a study has enrolled three dose cohorts
including 24 patients, 18 receiving drug and 6 receiving placebo.
Unblinded data is available for the first two cohorts. Cohort 3 data
collection is ongoing and this cohort remains blinded. Full results for
the first two dose cohorts at 1.0 mg/kg and 2.0 mg/kg and partial
(blinded) safety results from the 3.0 mg/kg dose cohort were included in
the poster.
In both studies, there have been no reports of serious AEs, no dose
limiting toxicities, no discontinuations due to AEs, and a modest
overall occurrence rate of AEs without a clear dose-related increase in
frequency or severity. There has been a modest occurrence rate of
non-clinically significant abnormal laboratory tests. There were no
reported drug related or clinically significant differences for vital
signs or ECGs between subjects receiving drug versus placebo. To date,
ARC-520 when administered as a single dose up to 4.0 mg/kg to healthy
volunteers and up to 3.0 mg/kg to patients with chronic HBV appears to
be well tolerated.
Arrowhead also reported initial results for depth and duration of
hepatitis B surface antigen (HBsAg) reduction in the Phase 2a study. In
cohort 1 (1.0 mg/kg), the mean nadir of HBsAg was -39% (range -22 to
-57) with a mean change on day 85 of -31% (range -14 to -39). In cohort
2 (2.0 mg/kg), the mean nadir of HBsAg was -51% (range -46 to -59) with
a mean change on day 85 of -22% (range -7 to -40). For cohort 2, the
percent reduction in HBsAg was statistically significant versus placebo
(p < 0.05) for days 3 through 43 post-dose. For cohort 2, the mean day
of HBsAg nadir was day 33 with a range of day 8 to day 57.
Arrowhead believes that this is the first time that a reduction in HBsAg
mediated through RNA interference has been demonstrated in patients with
chronic HBV infection. This study is ongoing with follow up continuing
on Cohort 3 (3.0 mg/kg) and recruitment underway for a fourth cohort of
patients at 4.0 mg/kg.
Preparations are underway to initiate a series of multi-dose Phase 2b
studies of ARC-520, for which the Company plans to file with regulatory
authorities in the fourth quarter of 2014. These studies are planned to
have clinical sites in the US, Western Europe, Asia, and potentially
other countries and/or regions. Several studies are currently
contemplated, including ARC-520 in combination with entecavir or
tenofovir as well as combination studies that add an immunostimulatory
agent.
ARC-AAT Data
Arrowhead also presented data on ARC-AAT, its clinical candidate for the
treatment of liver disease associated with Alpha-1 Antitrypsin
Deficiency (AATD), a rare genetic disease that severely damages the
liver and lungs of affected individuals. These patients synthesize a
mutant form of AAT (Z-AAT) in the liver which is poorly secreted and
accumulates, resulting in liver injury. The goal of treatment with
ARC-AAT is to silence production of Z-AAT thereby preventing further
accumulation of Z-AAT in the liver and potentially reversing
pre-existing liver injury and fibrosis.
The presentation in the prestigious Plenary Session titled, “A
hepatocyte-targeted RNAi-based treatment for liver disease associated
with alpha-1 antitrypsin deficiency,” was presented by Christine
Wooddell, Ph.D., Group Leader, Arrowhead Research. AASLD President Dr.
Adrian Di Bisceglie, MD, FACP also highlighted the presentation, along
with just ten others, in the President’s Press Conference as a program
that holds great promise for patients.
In preclinical studies with PiZ mice, which are genetically modified to
produce the mutant human AAT (Z-AAT), ARC-AAT induced a greater than 95
percent reduction in circulating AAT after a single dose with a long
duration of effect. Area covered by Z-AAT globules and globule size
within the liver were significantly reduced after a single dose of
ARC-AAT at day 15 post-dose (p < 0.005) and day 29 post-dose (p < 0.01).
Multi-dose studies in PiZ mice showed that ARC-AAT was effective at
reducing and preventing Z-AAT aggregates in the liver. At week 13 of the
study, after 4 biweekly doses, the ARC-AAT treated group show 99% less
soluble (monomer) Z-AAT and 79% less insoluble (polymer) Z-AAT,
normalized to a saline control group. Thus, injection of ARC-AAT in
transgenic mice expressing human Z-AAT resulted in prevention and
reduction of Z-AAT globules and, importantly, liver inflammation.
In primate studies, a 90% reduction of AAT in serum was observed after a
single injection, which persisted for over ten weeks with greater than
80 percent knockdown observed at the six-week time point. Multi-dose
studies in primates showed a sustained reduction of AAT with once every
six weeks dosing, suggesting that once monthly or less frequent dosing
may be sufficient to maintain approximately 80-90% knockdown in humans.
The treated animals showed no changes in clinical chemistry (ALT, AST,
BUN, Creatinine), indicating that ARC-AAT appeared to be well tolerated
at these optimal therapeutic dose levels.
About ARC-520
Arrowhead’s RNAi-based candidate ARC-520 is designed to treat chronic
HBV infection by reducing the expression and release of new viral
particles and key viral proteins. The goal is to achieve a functional
cure, which is an immune clearant state characterized by hepatitis B
s-antigen negative serum with or without sero-conversion. The siRNAs in
ARC-520 intervene at the mRNA level, upstream of where nucleotide and
nucleoside analogues act. In transient and transgenic mouse models of
HBV infection, a single co-injection of Arrowhead’s Dynamic
Polyconjugate (DPC) delivery vehicle with cholesterol-conjugated siRNA
targeting HBV sequences resulted in multi-log knockdown of HBV RNA,
proteins and viral DNA with long duration of effect. Arrowhead has
completed enrollment in a Phase 1 single ascending dose study in normal
volunteers. The company is conducting a single dose Phase 2a study in
chronic HBV patients, and expects to follow with multi-dose,
multi-national Phase 2b studies. Approximately 350 million people
worldwide are chronically infected with the hepatitis B virus. Chronic
HBV infection can lead to cirrhosis of the liver and is responsible for
80% of primary liver cancers globally.
About ARC-AAT
Arrowhead has developed ARC-AAT for the treatment of liver disease
associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic
disease that severely damages the liver and lungs of affected
individuals. ARC-AAT employs a novel unlocked nucleobase analog (UNA)
containing RNAi trigger molecule designed for systemic delivery using
the Dynamic Polyconjugate delivery system. ARC-AAT is highly effective
at knocking down the Alpha-1 antitrypsin (AAT) gene transcript and
reducing the hepatic production of the mutant AAT (Z-AAT) protein.
Reduction of liver production of the inflammatory Z-AAT protein, which
has been clearly defined as the cause of progressive liver disease in
AATD patients, is important as it is expected to halt the progression of
liver disease and potentially allow fibrotic tissue repair. The Company
plans to file with regulatory authorities in the fourth quarter of 2014
and commence clinical studies shortly after receiving permission to
begin.
About Arrowhead Research Corporation
Arrowhead Research Corporation is a biopharmaceutical company developing
targeted RNAi therapeutics. The company is leveraging its proprietary
Dynamic Polyconjugate delivery platform to develop targeted drugs based
on the RNA interference mechanism that efficiently silences
disease-causing genes. Arrowhead’s pipeline includes ARC-520 for chronic
hepatitis B virus, ARC-AAT for liver disease associated with Alpha-1
antitrypsin deficiency, and partner-based programs in obesity and
oncology.
For more information please visit http://www.arrowheadresearch.com,
or follow us on Twitter @ArrowRes.
To be added to the Company’s email list and receive news directly,
please visit http://ir.arrowheadresearch.com/alerts.cfm.
Source: Arrowhead Research Corporation
Arrowhead Research Corporation
Vince Anzalone, CFA
626-304-3400
ir@arrowres.com
or
Investor
Relations:
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Lauren Glaser
646-378-2972
ir@arrowres.com
or
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Partners
Martina Schwarzkopf, Ph.D.
212-845-4292
martina.schwarzkopf@russopartnersllc.com
Source: Arrowhead Research Corporation
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