Contributing Writer

Intradigm Corp. has been busy. In the last six months, the company raised $16 million, hired a new senior executive team and relocated its headquarters from Rockville, Md. to Palo Alto, Calif.

The $16 million round was a recapitalized Series A co-led by Alta Partners and Frazier Healthcare Ventures with participation from existing investors Emerging Technology Partners (ETP) and Novartis Venture Fund, as well as new investors MediBIC Alliance/Daiichi Pharmaceutical Co. Ltd. and Genentech Inc. The previously unannounced round closed in May, and by July the investors had recruited Mohammad Azab from QLT Inc. to serve as president and CEO. Azab quickly hired three vice presidents, opened the West Coast office and turned his attention to lead candidate ICS-283, a nanoparticle-based siRNA cancer treatment targeting the VEGF pathway.

Intradigm's goal is to have the first proof-of-concept data demonstrating targeted systemic delivery of RNAi therapeutics, Azab said. Proceeds from the current round should be sufficient to get there, and a clinical trial with ICS-283 is slated to begin before the end of 2007.

RNAi has received particular attention as of late, with Merck & Co. Inc. announcing plans to buy Sirna Therapeutics Inc. for $1.1 billion, and Alnylam Pharmaceuticals Inc., the other major player in the RNAi space, being the subject of some buyout speculation, too. The award of this year's Nobel Prize in Medicine to Craig Mello of the University of Massachusetts Medical School and Andrew Fire of Stanford University for their discovery of RNAi put the technology in the spotlight. (See BioWorld Today, Nov. 1, 2006, and Oct. 3, 2006.)

Mark Monane, analyst at Needham & Co., called RNAi "hot, hot, hot," but said the question now is whether the therapeutics will justify the excitement.

The promise of RNAi is its potential to silence RNA before it is translated into a disease-causing protein, but the hurdle lies in its delivery. When injected into the bloodstream, it is degraded and eliminated from the body, making it difficult to achieve the desired therapeutic affect in the target tissue. Thus far, much of the progress in RNAi has centered on applications where it can be delivered directly rather than systemically, such as through injections into the eye to treat age-related macular degeneration or inhalation into the lungs to treat respiratory diseases.

A multitude of companies have tried to apply various delivery mechanisms to RNAi, from liposomes to nanotechnology, but Monane said there is "no consensus on what is the best approach, and no one has emerged as the leader."

Intradigm's approach to addressing the RNAi delivery issue involves a layered nanoparticle with the RNAi molecule in its core and a ligand attached to its surface. The nanoparticle protects the RNAi from degradation so that it can travel through the bloodstream, the ligand directs it to the target tissue and a nucleic acid carrier delivers the active RNAi molecules into the cytoplasm of the target cells so that they are accessible to the RNAi machinery. In the case of ICS-283, the ligand used is an RGD peptide that targets αvß 3-expressing endothelial cells, inhibiting multiple targets within the VEGF pathway to create an anti-angiogenic affect.

"Intradigm has the components needed to build an RNAi therapeutics company, including both the novel RNAi technology and a targeted delivery platform, which is what has been missing," said David Mack, director of Alta Partners, adding that the company is his first "leap" into the RNAi space. Intradigm's technology is particularly applicable to cancer because it allows the targeting of multiple molecules, an approach that has proved successful with other oncology therapeutics such as multi-kinase inhibitors, Mack said.

Despite the significant interest both pharma and biotech have shown in the field, Azab said Intradigm plans to take ICS-283 through proof of concept without a partner. Once the approach is validated, the company will expand its pipeline by varying the RNAi molecules, targeting ligands and/or polymer modules within the core technology.

"We are already thinking about next-generation products," Azab said. "Once we know it works, successful delivery of RNAi opens a lot of doors for treating a variety of diseases."

In other financing news:

• Prana Biotechnology Ltd., of Melbourne, Australia, plans to raise A$7.8 million (US$6 million) by the end of the year through the sale of 21.8 million ASX-traded shares at A$0.357 per share (equivalent to 2.18 million Nasdaq-traded ADRs at $2.74 per ADR). An additional 4.35 million ASX-traded shares optioned at A$0.446 could bring in $1.5 million more. Following the financing, Prana will have $10.2 million in cash on hand with which to begin a Phase IIa trial of PBT2 in early Alzheimer's disease treatment. The trial will be conducted in Sweden and was green-lighted by Swedish regulatory authorities last month.