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InteRNA Technologies, Silence Therapeutics to Co-Develop miRNA Cancer Drugs

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By Doug Macron

InteRNA Technologies and Silence Therapeutics this week announced that they have forged a research and development collaboration to evaluate Silence's lipid-based drug-delivery technology with InteRNA's therapeutic microRNA mimics.

Under the deal, Silence will use its AtuPlex lipid vehicles to formulate undisclosed InteRNA miRNA sequences. Both companies will conduct in vitro and in vivo experiments on the agents and select lead drug candidates for further evaluation.

Silence will be paid undisclosed upfront fees and research payments. Additional terms were not disclosed.

According to InteRNA CEO Roel Schaapveld, the decision to partner with Silence was largely based on the groundwork already laid by the company related to its AtuPlex platform.

The technology is based on proprietary lipids that can embed an oligonucleotide into multiple lipid bilayer structures, resulting in a nanoparticle comprising a therapeutic payload, a cationic lipid, a fusiogenic lipid, and polyethylene glycol, according to Silence. In addition, the company has shown that the nanoparticles can be lyophilized to simplify handling and storage.

Importantly, AtuPlex has already demonstrated safety in the clinic as Silence nears completion of a phase I trial of Atu027, an siRNA-based cancer therapy delivered by the technology. Earlier this year, the company presented data from that study showing the drug to be safe and well tolerated at therapeutically relevant doses (GSN 6/9/2011).

In addition, Silence is capable of manufacturing AtuPlex nanoparticles in accordance with current good manufacturing practice standards, a “manufacturing bottleneck that a lot of drug-delivery technologies are [still] facing,” Schaapveld noted.

For its part, Silence sees the deal as a way to realize additional value from its delivery technology as it pursues its own RNAi drug candidates, a long-standing goal for the company.

At the time Silence released Atu027's phase I data, the firm's then-CEO Philip Haworth told Gene Silencing News that he hoped the findings would help get the attention of potential partners interested in using the delivery technology with their own drug candidates.

This week, Silence COO Thomas Christely noted in a statement that “it is in our interest to broaden the potential value of our AtuPlex delivery system as a vehicle to modify gene expression using different oligonucleotide classes, alongside our continuing focus on our internal siRNA therapies.”

Few details about the drug candidates covered by the collaboration with IntRNA have been publicly disclosed, but Schaapveld said that the deal will focus on miRNA mimics that are expected to have therapeutic potential in cancer, the company's primary therapeutic focus.

He is keeping wraps on the specific miRNAs that will be formulated with Silence's technology, but said that they are implicated in “signal-transduction pathways … [as well as] biological processes involved in cancer initiation and progression,” such as B-raf, p53, and Wnt.

He also noted that for each of InteRNA's programs, the company is experimenting with multiple miRNAs and has made the appropriate intellectual property filings.

In addition to the miRNA mimics covered under the Silence arrangement, InteRNA is considering developing miRNA inhibitors, Schaapveld said. It is looking into developing both standalone cancer treatments based on the small, non-coding RNAs, as well as ones that would be used in combination with existing small-molecule and antibody therapies as a way to address drug sensitivity and resistance.

At InteRNA, a handful of drug candidates are advancing out of the discovery stage and into formal preclinical testing, he said, and the company hopes to be ready to file an investigational new drug application by late 2013. Whether that first clinical candidate will be a miRNA mimic or antagonist, however, is unclear.

“We let the science determine what a candidate will be in the end,” Schaapveld said.


Have topics you'd like to see covered in Gene Silencing News? Contact the editor
at dmacron [at] genomeweb [.] com

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