Arrowhead Research ARC-520 Clinical Trials Soon

[djxpress]

Here's some info in the press release:

Arrowhead Research Advances ARC-520 into IND-Enabling Studies for the Treatment of Hepatitis B and Provides Guidance on Development Timeline


PASADENA, Calif. — June 6, 2012 — Arrowhead Research Corporation (NASDAQ: ARWR), a targeted therapeutics company, today announced that its hepatitis B virus (HBV) program has completed all internal preclinical requirements and has named a clinical candidate. As such, the Company has initiated the final IND-enabling steps, including GMP manufacturing, GLP toxicology, and preparation of a pre-IND data package for the US FDA and foreign counterparts. The candidate, named ARC-520, is an RNAi therapeutic actively targeted to the liver using the company's Dynamic Polyconjugate (DPC) delivery system and includes two siRNA sequences targeting two different regions of the HBV genome.
"Chronic HBV infection is a serious global health problem with no cure, and we believe ARC-520 can potentially have a substantial impact on patient care worldwide," said Dr. Bruce Given, Arrowhead's Chief Operating Officer and head of R&D. "We will continue to take an aggressive stance on development timelines for ARC-520. We anticipate filing an IND in Q2 of 2013 and our plan is to conduct a phase 1 clinical trial in chronic HBV carriers to provide early proof of concept."
The RNA sequences used in the clinical candidate were part of a large-scale screening program initiated by Roche prior to the acquisition by Arrowhead. The RNAs target regions highly conserved across the major HBV genotypes and ARC-520 contains two distinct RNAs as a strategy to minimize the potential development of resistance in individual patients. Consistent with the company's overarching strategy, the DPCs used in ARC-520 employ active ligand-mediated targeting specific to a receptor on hepatocytes. This approach results in high-potency knockdown of a target gene, validated in mice, rats, and non-human primates and it has demonstrated a low toxicity profile in primates enabling long term dosing.
"The promotion of ARC-520 as a clinical candidate, so soon after acquiring the Roche RNAi assets, represents an important milestone for Arrowhead," said Dr. Chris Anzalone, President and Chief Executive Officer of Arrowhead. "This program follows in the footsteps of our clinical stage targeted delivery programs in obesity with Adipotide® and in cancer with RONDELTM and further validates our commitment to ligand-mediated delivery in fields where most delivery is untargeted. We believe that targeting holds great promise in allowing delivery of currently undeliverable agents, such as many RNAs, and may also dramatically improve the balance of safety and effectiveness for many types of small molecule drugs."
Highlights from the preclinical development program for ARC-520 have been presented at recent scientific conferences and publication of additional data is anticipated over the coming months in peer-reviewed scientific journals.


Link: http://www.arrowres.com/publications/2012/june06_2012.html

[OrientS]

I hope the cure can be produced sooon ..
Cheap and available for everybody ..
We are waiting mercy of Allah ..

[djxpress]

Here's how their deliver method works:

Arrowhead Research Corporation (NASDAQ:ARWR - News) today announced that Darren Wakefield, Ph.D., one of its Senior Scientists at its Madison, WI research and development facility presented data at the TIDES: Oligonucleotide and Peptide Research, Technology and Product Development Conference in Las Vegas, NV. Dr. Wakefield’s poster presentation titled, “Liver-targeted and reversibly masked-polycation co-delivery improves cholesterol-conjugated siRNA efficacy,” describes the ability of Arrowhead’s PBAVE polymer to dramatically decrease the effective dose needed. PBAVE is one of the polymers included in Arrowhead’s proprietary Dynamic Polyconjugate (DPC) siRNA delivery platform.
“Linkage to cholesterol is one strategy that has been used by other siRNA therapeutic developers to prolong circulation time and to facilitate uptake into hepatocytes via the LDL receptor,” said Dr. Wakefield. “However, three daily injections of 50 mg/kg of cholesterol-conjugated apoB siRNA were previously required to achieve 50% gene silencing. Over the past few years, no real improvements have been reported to optimize the delivery of cholesterol or other lipophilic siRNA conjugates in vivo. Using our delivery technology, we are able to achieve similar gene silencing with a dramatically lower dose. This demonstration is one example of the potential of our DPC platform to broaden the utility and safety of siRNA therapeutics.”
Arrowhead’s chemists employed a new delivery approach to achieve similar gene silencing after a single injection of 0.2 mg/kg of cholesterol-conjugated siRNA, a 750-fold improvement in effective dose. This enhanced efficacy is attained by the co-delivery of an asiologlycoprotein receptor (ASGPr)-targeted and reversibly-masked cationic polymer, PBAVE. The injection of cholesterol-conjugated siRNA and modified-polymer can be temporally separated up to four hours without significant effects on gene silencing, suggesting that delivery does not depend on the association of targeted PBAVE and the cholesterol-conjugated siRNA in the blood. Genetic knockout of the ASGPr eliminates effective delivery of the cholesterol-conjugated siRNA, indicating that delivery depends on proper targeting of the PBAVE polymer.
About the Dynamic Polyconjugate siRNA Delivery Platform
Achieving safe and effective in vivo delivery of siRNA to the appropriate tissue and cell type is the primary barrier to development of RNAi as a therapeutic modality. Dynamic PolyConjugate (DPC) technology overcomes this barrier. Key features of the DPC technology include:
New classes of membrane-active and biodegradable polymers,
Reversible chemical masking of the polymers so that membrane-lytic activity is revealed only in the acidic environment of endosomes, and
The ability to attach ligands to guide the polymer and the siRNA cargo to specific cell types in vivo.
The utility of this technology has been demonstrated by ligand-mediated delivery of siRNA to liver hepatocytes in mice, rats, and non-human primates resulting in high-level knockdown of the targeted gene. Importantly, DPCs display a low toxicity profile enabling siRNA redosing and long-term target gene knockdown.