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Phase 1 CALAA-001 Clinical Trial Shows Systemic siRNA Delivery via Targeted Nanoparticles

Arrowhead Research Corporation (NASDAQ: ARWR) 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(TM), 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.

“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.”
.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.

“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.

Source: https://arrowheadpharma.com/

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