Arrowhead Presents Data on Potential RNAi Candidate Targeting Factor 12 Mediated Angioedemic and Thromboembolic Diseases
May 06 2015 - 3:15PM
Business Wire
Arrowhead Research Corporation (NASDAQ: ARWR), a
biopharmaceutical company developing targeted RNAi therapeutics,
today presented data at IBC’s 17th Annual TIDES Conference in San
Diego on the preclinical development of an RNAi therapeutic as a
potential treatment for factor 12 (F12) mediated angioedemic and
thromboembolic diseases. The presentation included data from in
vitro screenings, in vivo evaluations, a disease model, and a
multiple dose study in nonhuman primates. These data support
advancement of ARC-F12 as a potential new candidate in Arrowhead’s
growing pipeline of RNAi-based therapeutics enabled by the
company’s Dynamic Polyconjugate (DPC) delivery platform. A copy of
the presentation may be viewed on the Events and Presentations
section of the company’s website at
http://ir.arrowheadresearch.com/events.cfm.
"We see factor 12 as an extremely attractive target to add to
our pipeline. There is clear unmet need in thrombosis and
angioedema and the biology of factor 12 as part of the coagulation
cascade and the kinin-kallikrein system suggest that its reduction
through RNAi may present opportunities in both disease areas,” said
Christopher Anzalone, Ph.D., president and chief executive officer.
“We will be conducting additional studies in relevant disease
models shortly to provide us with further data to decide on the
advancement of ARC-F12 as a clinical candidate and initiation of
IND enabling studies.”
David Lewis, Ph.D., chief scientific officer, presented initial
data from wild type mice, showing that various RNAi triggers
selected from in vitro screening sets and co-administered with DPCs
achieved significant and sustained knockdown of F12 levels of
greater than 99% at nadir for most triggers. Strategic
incorporation of various modifications to the most potent RNAi
trigger increased the depth and duration of F12 knockdown activity
as shown in dose response studies. In a study in mice, these
modified triggers exhibited a dose-dependent increase in F12
knockdown. A single intravenous dose of 0.5 mg/kg reduced F12 by
greater than 80%. When the dose was increased to 2 mg/kg, the
reduction increased to greater than 95% at nadir, with greater than
70% knockdown observed at the one month time point. The lead RNAi
trigger was also highly active in multiple dose nonhuman primate
studies. With four intravenous doses of 2 mg/kg given once every
four weeks, approximately 90% F12 knockdown was achieved after the
first dose with even greater knockdown following subsequent doses.
Knockdown was also highly durable with greater than 80% reduction
maintained between monthly doses. The combination of RNAi trigger
and DPC appeared to be generally well-tolerated and no drug-related
changes in toxicity markers were observed as measured by clinical
chemistry and hematologic parameters.
Dr. Lewis also presented data from a relevant disease model on
the lead RNAi trigger and DPC combination. In this mouse model,
thromboembolism is induced by exposure of carotid artery to ferric
chloride. The time to blood flow occlusion is then measured as a
clinically relevant indicator of physiological response to F12
knockdown. Animals were treated with saline or the lead RNAi
trigger and DPC combination 15 days prior to ferric chloride
challenge. Treated animals showed approximately 99% knockdown in
serum F12 levels at Day 15 relative to baseline, while animals
receiving saline showed no reduction. A dramatic increase in
occlusion times as a measure of the inhibition of thrombus
formation was observed in treated mice.
Arrowhead believes that ARC-F12 may present opportunities to
target multiple diseases, including in thrombosis. The company is
currently planning to investigate ARC-F12 in hereditary angioedema
(HAE) as the first target indication. HAE is a rare genetic
disorder with a prevalence of approximately 1/5,000-1/10,000 that
is most commonly caused by mutations in the complement factor 1
esterase inhibitor gene (C1INH). Patients with HAE can experience
recurrent and dangerous acute inflammatory attacks in multiple
tissues, with attacks of laryngeal edema being particularly serious
and potentially fatal. Current treatments seek to reduce the
severity, duration, and frequency of acute HAE attacks, but
frequent intravenous dosing of 1-3 times weekly is required and
many patients do not respond adequately. Arrowhead believes the
novel mechanism of ARC-F12 may fill an unmet need for patients and
physicians who desire long term prophylaxis and may view
intravenous dosing every 4-6 weeks as a significant advance.
The company is currently planning additional evaluation of
ARC-F12 in relevant HAE disease models including C1INH knockout
animals and captopril-induced vascular leak, among potential other
studies to support advancement of ARC-F12 into IND enabling
studies.
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 and ARC-AAT for
liver disease associated with Alpha-1 antitrypsin deficiency.
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.
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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 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, actions of the U.S. Food
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rapid technological change in our markets, challenges to the
validity of our intellectual property rights, and the enforcement
of our intellectual property rights. Arrowhead Research
Corporation's most recent Annual Report on Form 10-K and subsequent
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Source: Arrowhead Research Corporation
Arrowhead Research CorporationVince Anzalone,
CFA626-304-3400ir@arrowres.comorInvestor Relations:The Trout
GroupTodd James646-378-2926ir@arrowres.comorMedia:Russo
PartnersMatt Middleman,
M.D.212-845-4272matt.middleman@russopartnersllc.com
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