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With Abbott as Its First RNAi Partner, Liquidia Remains on the Lookout for Additional Alliances


Having just forged its first alliance in the RNAi field with Abbott, Liquidia Technologies remains on the lookout for other companies interested in using its nanoparticle design and manufacturing platform to make drugs based on the gene-silencing technology, a company official told RNAi News last week.

However, Liquidia COO Luke Roush added that the company does not expect to begin any in-house RNAi programs in the foreseeable future.

Earlier this month, Liquidia announced that it had signed a deal giving Abbott access to its so-called PRINT, or Pattern Replication In Non-wetting Templates, technology to help it develop siRNA-based therapeutics (see RNAi News, 1/8/2009).

Still, the company is "absolutely going to be looking for other partners," Roush told RNAi News this week. "An important element of the deal for us [was that we'd] be able to do other partnerships in the [RNAi] field."

According to Roush, the Abbott deal marked a key milestone in his company's bid to find new applications for a technology born out of the semiconductor industry.

"For the first time in the last four or five years, the size of [semiconductor-related devices] … is biologically relevant," he told RNAi News last week. "We're taking advantage of that convergence of two fields that haven't really communicated a whole lot."

Roush said that Liquidia had been looking for life-science opportunities for its PRINT technology for some time, but the company wasn't entirely sure how to use it. "One of the things that we quickly arrived at is that we wanted to play in markets … where big pharma has a problem and needs solutions," he added.

And when it comes to therapeutic RNAi, delivery is perhaps the biggest hurdle to overcome.

The PRINT platform, Roush said, involves making templates of specific patterns, on which a proprietary non-stick polymer is applied to create a mold. "We can fill the cavities of the mold with any material … [and] once we fill the mold with a particular substance, we have a method … to go in and harvest … [the resulting] discrete, free-standing particles," he said.

"We're essentially printing two-dimensional arrays of nanoparticles," Roush added. "At the end of the day, it's kind of simple; we're just molding particles. But the material we make those particles out of, the size, the shape, the chemistry, the surface functionality, the flexibility of the particles — those are all attributes that we can tune."

In doing so, he said, the company expects to not only be able to create delivery vehicles for new classes of therapeutics, such as ones based on RNAi, but also for existing drugs in order to improve their performance.

"By being able to tune these different aspects of the delivery vehicle, we're able to create a lot of value in [different] drugs," Roush said. "For example, there are certain sizes and shapes of particles that, based on our research, circulate in the body for longer periods of time.

"In the example of cancer … if we can circulate for longer periods of time, we can get higher rates of accumulation of a drug in a tumor and lower accumulation in other parts of the body … [while avoiding] some of the off-target toxicities associated with other chemotherapeutic approaches," he added.

And it is precisely in the cancer field that Abbott hopes to be able to use the PRINT technology.

The company first stepped into the RNAi arena in mid-2006 when it signed an agreement to work with Dharmacon to develop siRNA-based drugs for multiple indications, with an initial focus on cancer (see RNAi News, 7/13/2006). Roush confirmed that Liquidia's arrangement with Abbott is specific to cancer, but declined to comment further on the details of the collaboration.

He did note that Liquidia is free to pursue partnerships in other disease states. "For other pharmaceutical companies that have core competencies in areas outside of cancer, we wanted to be able to preserve our partnering potential," he noted.

One area Roush said Liquidia is particularly interested in exploring is pulmonary delivery of siRNAs.

In addition to in vitro and in vivo studies in which Liquidia has demonstrated that it can use PRINT particles to knock down target gene expression, the company has conducted experiments showing that it can manufacture nanoparticles "to fly a certain way in the lung and [in order to] improve the respirable dose of a drug that is delivered to the lungs," he said. "There is certainly some additional work that needs to be done to follow on our initial work, but we feel very optimistic that we're on the right path."

To Liquidia, that additional work will best be done in collaboration with a partner, and "in the near term, we're going to be more partnership-focused than we are internal-development focused," Roush noted.

RNAi-based drug delivery is "an area where we felt there was significant unmet need and it is an area where we felt our technology is significantly differentiated from competing technologies," he said. "It's a new therapeutic area; there is a lot of promise with huge potential returns, but [there is] still a lot of risk.

"So, we ultimately decided that rather than trying to get access to chemistry to do our own drug, we initially wanted to partner with somebody else and learn with them rather than on our own," he added.

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