Calando Pharmaceuticals Announces Initial RNAi Product, Goals for 2007

PASADENA, California – September 6, 2006 – Calando Pharmaceuticals Inc., a leading RNAi Therapeutics company and majority-owned subsidiary of Arrowhead Research Corporation (NASDAQ: ARWR), today provided more detail on its product and business goals for 2007.   

“We have made considerable progress since we commenced operations in mid-2005 – we set very ambitious goals for Calando in 2005 and 2006 to lay the foundation for our product pipeline and future partnerships,” said John Petrovich, President and Chief Executive Officer of Calando.  “In 2007, we will build on this foundation by continuing to advance our first experimental RNAi therapeutic toward clinical trials, in hopes of commencing Phase I trials before the end of the year.”

According to Calando Chief Scientific Officer, Dr. Jeremy Heidel, Calando’s first RNAi therapeutic would direct the silencing of a gene implicated in a wide variety of solid tumors. “Our success in pre-clinical studies involving different types of cancer cells provides us with optimism about the prospects of treating numerous types of cancer patients with this therapeutic.”
 
Calando’s first therapeutic contains a targeting ligand the cell surface receptor for which is over-expressed on a wide variety of different cancers. The combination of a generalized gene target and a generalized cell surface receptor targeting ligand endow Calando’s therapeutic with features that make it potentially applicable for the treatment of a broad spectrum of solid cancers.

In addition to identifying the initial gene target for its first therapeutic, Calando has:

• Filed for patent protection of its siRNA sequences for the gene target, and licensed key siRNA patents from Alnylam Pharmaceuticals.
• Established scale-up and manufacturing relationships for both the siRNA component and Calando’s proprietary cyclodextrin-polymer delivery system, and ordered materials for IND-enabling toxicity studies and cGMP materials for its Phase I trial.  Manufacturers include Agilent Technologies, Cambrex and SunBio.
• Established safety profile for the complete therapeutic, systemically administered in non-human primates. 

Calando is currently planning to file an Investigational New Drug (IND) application with the US Food and Drug Administration, and upon clearance of regulatory requirements and institutional review by the clinical trial site, Calando hopes to begin its first clinical trial at a leading Southern California cancer center before the end of 2007.  The company believes that this clinical trial will be the first targeted siRNA therapeutic against cancer to reach the clinic. 

“Calando’s therapeutic is a targeted RNAi therapeutic designed de novo”, said Dr. Mark Davis, Caltech professor and Calando Founding Scientist. “It combines synthetic delivery components with targeting agents and siRNAs that do not require chemical modification to create the first of its kind nanoparticulate therapeutic for cancer.  The therapeutic is an ‘intelligent’ nanoparticle that has shown excellent safety and lack of immunostimulatory effects in rodent and non-human primate studies.  We are excited to transition targeted siRNA-based therapeutics to the clinic as all in the field realize that effective, targeted delivery is the holy grail.”

Calando also hopes to announce an additional development candidate in the second half of 2007, as it continues to expand its pipeline of RNAi therapeutics programs. 

About RNA Interference (RNAi)

RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes.  Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases.  RNAi is induced by small, double-stranded RNA molecules.  One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene.  The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

About Calando Pharmaceuticals Inc.

Calando Pharmaceuticals Inc. (www.calandopharma.com) is using its proprietary technologies in targeted polymeric delivery systems and siRNA design to design and create new, targeted siRNA therapeutics. Small interfering RNAs (siRNA) induce RNA interference, or RNAi, a naturally occurring mechanism within cells to selectively silence and regulate specific genes. The ability to silence genes through RNAi could provide a new way to treat a wide range of human diseases. The company is pursuing this goal through its internal research and development and also through collaborations and partnerships with pharmaceutical and biotechnology companies.

Calando Technology

Calando’s cyclodextrin-containing polymers form the foundation for its two-part siRNA delivery system. The first component is a linear, cyclodextrin-containing polycation that, when mixed with small interfering RNA (siRNA), binds to the anionic “backbone” of the siRNA. The polymer and siRNA self-assemble into nanoparticles of approximately 50 nm diameter that fully protect the siRNA from nuclease degradation in serum. The siRNA delivery system has been designed to allow for intravenous injection. Upon delivery to the target cell, the targeting ligand binds to membrane receptors on the cell surface and the RNA-containing nanoparticle is taken into the cell by endocytosis. There, chemistry built into the polymer functions to unpackage the siRNA from the delivery vehicle. In addition to targeting tumors, the targeting of liver cells has also been accomplished in vivo.

Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the recent economic slowdown affecting technology companies, the future success of our scientific studies, our ability to successfully develop products, rapid technological change in our markets, changes in demand for our future products, legislative, regulatory and competitive developments and general economic conditions. Our Annual Report on Form 10-K and 10-K/A, recent and forthcoming Quarterly Reports on Form 10-Q and 10-Q/A, recent Current Reports on Forms 8-K and 8-K/A, our Registration Statement on Form S-3, and other SEC filings discuss some of the important risk factors that may affect our business, results of operations and financial condition. We undertake no obligation to revise or update publicly any forward-looking statements for any reason.

Contacts

Ed Jacobs, CEO
Telephone: 626.683.7200
Email: ejacobs@insertt.com