Arrowhead Pharmaceuticals Presents New Data on ARC-F12 and ARC-LPA Using DPCsqTM Subcutaneous RNAi Delivery Vehicle

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Arrowhead Pharmaceuticals Presents...

PASADENA, Calif.–(BUSINESS WIRE)–

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today delivered oral

presentations on ARC-LPA, its preclinical development program targeting

lipoprotein (a), for the treatment of cardiovascular disease, and

ARC-F12, its preclinical development program targeting factor XII (F12)

for the prophylactic treatment of thromboembolism and hereditary

angioedema, at the American Heart Association’s Scientific Sessions 2016

in New Orleans. These data show advancements being made in the ARC-LPA

and ARC-F12 programs and in the development of Arrowhead’s proprietary

DPCsqTM delivery vehicle designed for

subcutaneous administration of RNAi therapeutics.

Chris Anzalone, Ph.D., president and CEO of Arrowhead Pharmaceuticals,

said: “We have made rapid advancements to our DPCsqTM

subcutaneous RNAi delivery platform. F12 and Lp(a) are both very

attractive targets for RNAi, and the data presented today on ARC-F12 and

ARC-LPA show substantial improvements in activity over previous

generations. In addition, through multiple rounds of SAR studies,

substantial gains in potency continue to be made by Arrowhead

scientists. Data shown today are from the first and second generation

triggers. Studies that are ongoing in NHPs that use our fourth

generation RNAi triggers and the DPCsqTM platform,

are achieving even higher levels of target knockdown with longer

duration using lower and less frequent doses (data not shown).”

The oral poster titled, “Targeting factor XII (F12) with a novel RNAi

delivery platform as a prophylactic treatment for thromboembolism“,

describes advancements in the preclinical development of ARC-F12. Key

details of the presentation include the following:

  • F12 is an attractive target for an RNAi therapeutic

    • It is key component at the top of the contact (intrinsic)

      coagulation cascade

    • It is predominantly expressed in the liver and circulates in blood

    • Inhibition is genetically validated and deficiency protects from

      thromboembolic disease but is not associated with either bleeding

      or thrombotic disorders

  • Arrowhead developed RNAi triggers that gave greater than 95%

    reductions of serum F12 levels after a single subcutaneous injection

  • Dose dependent reductions in serum F12 levels were observed with

    single injections of ARC-F12 of 1 mg/kg and 3 mg/kg leading to mean

    reductions of 86% and 96% respectively

  • A statistically significant reduction (p=0.002) in thrombus weight was

    observed at greater than 95% F12 knockdown in a rat arterio-venous

    shunt model

  • There was no increased bleeding risk in ARC-F12 treated mice, even

    with greater than 99% knockdown of F12 levels

The oral presentation titled, “Targeting apolipoprotein(a) with a

novel RNAi delivery platform as a prophylactic treatment to reduce risk

of cardiovascular events in individuals with elevated lipoprotein (a)“,

describes advancements in the preclinical development of ARC-LPA, which

is part of a recently announced license and collaboration agreement with

Amgen. Key details of the presentation include the following:

  • Lipoprotein (a) [Lp(a)] is an attractive target for an RNAi therapeutic

    • Lp(a) is an independent risk factor for cardiovascular disease

      through its atherogenic potential

    • Higher levels of Lp(a) correlate with increased risk of

      cardiovascular disease

    • Lp(a) levels in humans are genetically defined and do not change

      significantly with diet and exercise

    • Approximately 25% of the U.S. population has greater than 30 mg/dL

      of Lp(a) (normal levels: 0.1 – 25 mg/dL)

    • It is predominantly expressed in the liver and circulates in blood

  • Screening of LPA RNAi triggers in Lp(a) transgenic (Tg) mice

    identified several that induced substantial and sustained knockdown of

    serum Lp(a) levels

  • Structure activity relationship (SAR) studies assessing structure and

    chemical modifications identified triggers that achieved greater than

    98% maximum knockdown after a single 3 mg/kg SQ dose in Tg mice

  • In NHPs, 85-90% reduction of serum Lp(a) levels was observed after

    three weekly 3 mg/kg SQ doses

  • In an atherosclerosis model, data suggest that RNAi triggers can be

    effectively delivered to a fatty liver using the DPCsqTM

    platform

A copy of presentation materials will be made available on the Events

and Presentations page under the Investors section of the Arrowhead

website.

About ARC-F12

Arrowhead’s RNAi-based candidate ARC-F12 is in preclinical development

as a potential treatment for factor XII (F12) mediated diseases.

Arrowhead sees clear unmet need in hereditary angioedema (HAE) and

thromboembolic diseases. 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.

The company is currently conducting studies in order to advance ARC-F12

into clinical trials.

About ARC-LPA

Arrowhead’s RNAi-based candidate ARC-LPA is in preclinical development

as a potential treatment for cardiovascular diseases. ARC-LPA is

designed to reduce production of apolipoprotein(a), a key component of

lipoprotein(a), or Lp(a). Lp(a) levels in humans are genetically defined

and higher levels correlate with increased risk of cardiovascular

diseases, independent of cholesterol and LDL levels. ARC-LPA is

Arrowhead’s first drug candidate to use a subcutaneously administered

delivery construct.

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. The company’s pipeline includes ARC-520 and ARC-521 for

chronic hepatitis B virus infection, ARC-AAT for liver disease

associated with alpha-1 antitrypsin deficiency, ARC-F12 for hereditary

angioedema and thromboembolic disorders, ARC-LPA for cardiovascular

disease, and ARC-HIF2 for renal cell carcinoma.

For more information, please visit www.arrowheadpharma.com,

or follow us on Twitter @ArrowheadPharma.

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DYNAMIC POLYCONJUGATES is a trademark of Arrowhead

Pharmaceuticals, Inc.

Source: Arrowhead Pharmaceuticals, Inc.

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

Relations:
The Trout Group
Chad Rubin
646-378-2947
ir@arrowheadpharma.com
or
Media:
Russo

Partners
Matt Middleman, M.D.
212-845-4272
matt.middleman@russopartnersllc.com

Source: Arrowhead Pharmaceuticals, Inc.

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