Ready and aiming

PASADENA, Calif.—Arrowhead Research Corp., a nanomedicinecompany with development programs in RNAi therapeutics and obesity, and AxolabsGmbH, a custom research organization offering preclinical solutions andconsultancy in the field of oligonucleotide therapeutics, have entered into astrategic alliance and master services agreement.

"This agreement continues the execution of Axolabs' strategyto become the preeminent custom research organization in the oligonucleotidetherapeutics field," says Dr. Roland Kreutzer, managing director of Axolabs."We know the colleagues at Arrowhead very well. We are happy to support them inestablishing a leading role in the area of RNAi therapeutics and excited to bechosen as their preclinical service provider."

Under the terms of the agreement, Axolabs, founded by theprincipals of the former Roche Center of Excellence for RNAi Therapeutics inKulmbach, Germany, will provide Arrowhead and its partners with oligonucleotideoptimization, synthesis and analytics. These services include bioinformaticsfor siRNA design; lead identification, optimization and characterization; aswell as siRNA synthesis and CMC-related activities.

"With multiple candidates in the clinic addressing a widerange of indications, data demonstrating the power of RNAi as a therapeuticmodality are rapidly accumulating," says Dr. Christopher Anzalone, Arrowhead'sCEO. "Having access to Axolab's expertise in preclinical developmentcomplements Arrowhead's capabilities well and provides us with yet another toolfor preclinical and clinical collaborations in the field. Now, with thecompany's already established intellectual property position and array ofproprietary delivery technologies, including Dynamic PolyConjugates (DPC) andRONDEL, Arrowhead is uniquely positioned to build its own pipeline of RNAitherapeutics and provide partners entry to this promising area in a rapid andcost-effective manner."

Arrowheadhas used a nontransgenic mouse model of chronic HBV infection of the liver totest the efficacy of its DPC technology for delivery of anti-HBV siRNAs. Thesemice produce HBsAg and HBV viral particles that are secreted into the blood. Asa prelude to successful clinical development and commercialization, Arrowheadhas secured a license granting it the exclusive right to develop, manufactureand commercialize siRNA therapeutics against the HBV genome to treat HBV fromAlnylam Pharmaceuticals Inc.

AlnylamPresident and Chief Operating Officer Barry Greene notes that there are threeknown modes for overcoming the delivery hurdles that have confronted RNAitherapeutics, liposome nanoparticles and chemistry conjugates (both Alnylam's),and Arrowhead's Dynamic PolyConjugates approach. In addition, there isArrowhead's RONDEL technology—new targeted, siRNA-containing therapeutics thatemploy a proprietary three-part RNAi/Oligonucleotide Nanoparticle Delivery(RONDEL) system, the foundation of which is a cyclodextrin-containingpolymer.

"Naked"siRNA is degraded and destroyed by nucleases in the bloodstream and is nottaken up by cells, and also causes harmful immune reactions. The RONDELsystem's cyclodextrin-containing polymers protect thesiRNA and allow it to reach its destination and perform its intendedjob; for example, to stop the runaway growth of tumor cells.

Greenepoints out that RNAi represents a whole new class of therapies that have thenear-term potential to transform a number of diseases. One he points to is TTR-mediatedamyloidosis (ATTR), in which Alnylam is developing ALN-TTR, a systemicallydelivered RNAi therapeutic that targets the transthyretin (TTR) gene, to treatATTR.

ATTRis caused by mutations in the TTR gene, which is expressed predominantly in theliver, and results in the accumulation of pathogenic deposits of mutant andwild-type TTR protein in multiple extra-hepatic tissues, including theperipheral nervous system, heart, and the gastrointestinal tract.

"Asthere are currently few options for patients suffering from this devastatingdisease, we aim to rapidly advance our ALN-TTR program and are committed tobringing this important medicine to ATTR patients in need," he states.