Assistant Managing Editor

Promising preclinical data with its RNAi-based platform in liver and bladder cancers, combined with an early stage collaboration, sent MDRNA Inc. skyrocketing Wednesday in what could be a sign of news to come from the Bothell, Wash.-based company in 2010.

The firm hopes to "establish one R&D collaboration by the middle of the year and a second by the end of the year," said President and CEO Michael French during a presentation at the 2010 OneMedForum held just across the street from the larger J.P. Morgan conference in San Francisco.

MDRNA also plans to file its first investigational new drug application for an RNAi-based therapy in oncology by the end of 2010. It hasn't yet decided on a specific indication, but French said it's likely to be bladder cancer.

New in vivo data from a UsiRNA - what MDRNA calls its duplex siRNAs modified with unlocked nucleobased analogues - targeting polo-like kinase 1 (PLK1), a protein involved in cell mitosis and tumor progression, showed that local, intravesical administration resulted in a dose-dependent decrease in bioluminescence in a mouse model of orthotopic bladder cancer.

Data showed a greater than 90 percent reduction at a dose of 1 mg/kg.

Targeting PLK1 showed efficacy in models of orthotopic liver cancer and subcutaneous liver tumors, as well.

Investors jumped on those data, with high-volume trading in MDRNA pushing the company's shares up as much as 83 percent at market open. The stock (NASDAQ:MRNA) closed at $1.39, up 44 cents, or 46.5 percent.

It's not the first time one of MDRNA's early candidates has impressed in preclinical studies. The firm previously reported data from an UsiRNA designated MRNA-046 showing activity in both liver and bladder cancers. That drug is designed to target survivin, a protein involved in apoptosis.

But the advantage would be in combining those targets - PLK1 and survivin - and possibly others. "We believe we can use multiple siRNAs in the same formulation for a single-drug compound to go after multiple pathways in tumor growth," French said.

The siRNAs are delivered via MDRNA's delivery platform, DiLA2, which creates liposomes from dialkyl-amino acids.

That delivery technology already has caught the attention of at least one big pharma. Basel, Switzerland-based Novartis AG paid $7.25 million up front last year for a nonexclusive license. (See BioWorld Today, March 24, 2009.)

Also last year, MDRNA signed a deal with F. Hoffmann-La Roche Ltd., also of Basel, granting a nonexclusive license to a portion of its technology platform for development of RNAi-based drugs.

Terms of that deal were not disclosed.

While those deals were positive steps for MDRNA last year, as it worked to complete its transition from a firm struggling with an intranasal drug pipeline to one working in the increasingly popular RNAi field, French said it's not "in our business model to continue to license the technology."

Instead, the goal will be to enter large collaborations involving such terms as "$10 [million] to $20 million up front with downstream milestones and royalties," he said.

To that end, the company has signed two early collaborations, one in September and the most recent announced Wednesday with an undisclosed pharma firm. The goal is to establish relationships with the pharmas and, hopefully, grow it into a larger deal, French said.

MDRNA, which reported a third-quarter net loss of $7 million, or 17 cents per share, ended that quarter with about $4.6 million in cash, though it brought in another $1 million in a December bridge loan to take it to an anticipated collaboration.