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Posted: June 1, 2010

Arrowhead Research Announces Clinical Data Presentations at the 2010 ASCO Annual Meeting

(Nanowerk News) Arrowhead Research Corporation today announced that interim data from the phase 1 clinical trial conducted by its majority-owned subsidiary, Calando Pharmaceuticals, will be presented at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting. The trial involves Calando's therapeutic candidate CALAA-01, a formulation of its proprietary delivery system, RONDEL™, and an siRNA sequence targeting cancer. Dr. Antoni Ribas of UCLA's Jonnson Comprehensive Cancer Center will discuss the data in a poster presentation on Sunday, June 6, 2010 at 5:00 p.m. Eastern time.
An abstract with the clinical study data, entitled "Systemic Delivery of siRNA via targeted nanoparticles in patients with cancer: Results from a first-in-class phase 1 clinical trial" (Abstract No. 3022) will also be presented at the Developmental Therapeutics - Experimental Therapeutics Session on Sunday, June 6 from 2:00 p.m. to 6:00 p.m. The abstract can be accessed at ASCO's site at: http://abstract.asco.org/AbstView_74_44614.html.
"As the first proof-of-concept data demonstrating systemic siRNA delivery and gene silencing via RNAi in humans, these data represent an important milestone for our Company and for the broader RNAi industry," said Dr. Christopher Anzalone, Arrowhead's Chief Executive Officer. "RONDEL is a flexible delivery system that we believe will ultimately enable multiple RNAi therapeutics, and we are encouraged by what we have seen with CALAA-01."
Dr. Ribas said, "Given the longstanding hurdles with effective systemic delivery of siRNA in humans, these exciting data represent a significant step for the field of RNAi. Detection of RONDEL siRNA nanoparticles inside cells biopsied from tumors demonstrates that RONDEL is capable of shuttling siRNA into tumors after being infused into the bloodstream of patients. We have also seen mRNA and protein knockdown as well as the presence of RONDEL inside tumors in a dose-dependent manner, both of which are excellent indications of effective systemic delivery. While much work remains to be done, these findings suggest that the RONDEL delivery system's approach could be expanded for use as a means for drug delivery and treatment for many cancer therapy targets that are currently considered untreatable."
The Phase I CALAA-001 clinical trial is being conducted at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles, CA and at START (South Texas Accelerated Research Therapeutics) in San Antonio, TX. The trial is an open-label, dose-escalating study of intravenously administered CALAA-01 in adults with solid tumors, who have failed other standard-of-care treatments. In 15 patients treated with CALAA-01 to date, no dose limiting toxicities were observed. One patient at the highest dose level had stable metastatic melanoma for four months, a change from prior course. Biopsies from three patients showed CALAA-01 nanoparticles in tumors in amounts that correlate with dose levels. Additionally, a reduction of target messenger RNA and target protein was observed and at the highest dose, the targeted protein was knocked down with confirmation of mechanism by specific cleavage sequence (RACE-PCR). The study's authors conclude that systemic delivery of siRNA via targeted nanoparticles has been well tolerated and can induce specific, siRNA-mediated gene silencing. The study is ongoing and patients continue to be enrolled at escalating doses. The Company expects to complete the Phase I study by the end of the 2010 calendar year.
About RONDEL
Calando's RONDEL delivery system extends the reach of RNAi therapeutics by answering the new field's most pressing need -- an effective and safe systemic delivery method.
The RONDEL system takes advantage of molecular forces that generate self-assembly of an siRNA containing nanoparticle therapeutic. Comprised of three components and siRNA, the system is engineered to form targeted, stabilized, siRNA-containing nanoparticles of less than 100nm in diameter that target specific tissues and fully protect the siRNA from degradation in serum.
Upon delivery to the target cell, the nanoparticle binds to membrane receptors on the cell surface and the siRNA-containing nanoparticle is taken into the cell by endocytosis. There, chemistry built into the system unpacks the siRNA from the delivery vehicle. The siRNA is deposited into the cytoplasm of the cell where it can access the cellular machinery for RNA interference.
Benefits of the RONDEL system include more effective delivery, modular design to allow easy exchange of the active siRNA ingredient and targeting agent, fewer immune reactions and increased stability. RONDEL is also designed to work with human physiology and cell biology to overcome the extra- and intra-cellular barriers to siRNA delivery.
About CALAA-01
CALAA-01, Calando's leading drug candidate, is a combination of RONDEL™ and a patented siRNA targeting the M2 subunit of ribonucleotide reductase, a clinically-validated cancer target. Ribonucleotide reductase catalyzes the conversion of ribonucleosides to deoxyribonucleosides and is necessary for DNA synthesis and replication; it is a critical component in the proliferation of cancer cells. Calando's siRNA and CALAA-01 have demonstrated potent anti-proliferative activity across multiple types of cancer cells. The targeting agent in CALAA-01 is transferrin, a blood plasma protein for iron delivery. Transferrin receptors have been shown to be up regulated in many types of cancer cells.
About the CALAA-01 Phase I Trial
This is an open-label, dose-escalating study of the safety of intravenous CALAA-01 in adults with solid tumors refractory to standard-of-care therapies. Patients who satisfy the inclusion and exclusion criteria receive two, 21-day cycles of CALAA-01. A cycle consists of four infusions administered on days 1, 3, 8, and 10 followed by 11 days of rest. If safe, a second 21-day cycle is administered consisting of infusions on days 22, 24, 29, and 31 followed by 11 days of rest. For information about the CALAA-01 clinical trials, please visit www.clinicaltrials.gov.
About Arrowhead Research Corporation
Arrowhead Research Corporation (www.arrowheadresearch.com) is a nanotechnology company commercializing new technologies in the areas of life sciences and electronics. Arrowhead is seeking to build value for shareholders through the progress of its subsidiaries and investments. Currently, Arrowhead is focused primarily on its two majority owned subsidiaries; Unidym, a leader in carbon nanotube technology for electronic applications, and Calando, at the forefront of clinical application of RNAi delivery technology. Arrowhead also has minority investments in two privately held nanobiotech companies.
About Calando Pharmaceuticals, Inc.
Calando (www.calandopharma.com), a majority-owned subsidiary of Arrowhead Research Corporation, is a clinical stage nanobiotechnology company at the forefront of RNAi therapeutics. Calando develops nanoparticle therapeutics that use patented sugar (cyclodextrin)-based polymer technologies as a drug delivery system for siRNA. Engineered to reduce the debilitating effects of cancer treatment, the proprietary molecules are designed to improve the safety and efficacy of cancer therapeutics using siRNA as the active ingredient. The target-agnostic platform technology has the potential to be applied to a wide range of diseases beyond cancer as well as to therapeutic classes beyond siRNA therapeutics.
Source: Arrowhead Research Corporation
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