By Doug Macron
This story has been updated to include company comment on its newly announced bladder cancer program.
MDRNA has begun non-human primate studies within its lead liver cancer program with the goal of selecting a lead drug candidate by the end of the year and potentially filing an investigational new drug application by late 2010, a company official said last week.
At the same time, the company has expanded its pipeline to include bladder cancer after achieving positive results in rodent studies conducted through a partnership with the University of British Columbia, and could file an IND from this program as early as the end of 2011, the official added.
MDRNA also reported its second-quarter financial results last week, posting a nearly 50 percent drop in its net loss despite decreased revenues. The company attributed the improvement to decreased costs following its completed transition from the clinical-stage intranasal drug-delivery shop Nastech Pharmaceuticals to a preclinical RNAi-therapeutics developer.
Although it had initially intended to pursue a variety of different indications (see RNAi News, 8/7/2008), earlier this year MDRNA said that it would work exclusively on liver cancer as a way to conserve cash in a difficult economy (see RNAi News, 3/26/2009).
That sharpened focus appears to have paid off. Speaking last week during a conference call held to discuss MDRNA's second-quarter results, CSO Barry Polisky noted that the company has been able to demonstrate "efficient delivery and effective knockdown of multiple targets in rodents," including an in-house rodent model of the liver cancer.
In February, the company reported that its UsiRNAs — duplex siRNAs modified with non-nucleotide acyclic monomers, called unlocked nucleobase analogs, in which the bond between two adjacent carbon atoms of ribose is removed — were capable of triggering significant inhibition of apolipoprotein B in a rodent model.
A few months later, the company said that UsiRNAs were able to inhibit expression of the blood-clotting factor Factor VII in rodents by more than 90 percent with a duration of effect lasting up to 28 days.
"We've demonstrated that our DiLA2 [liposomal delivery] platform is well-tolerated and safe in rodent models, and … we have established a robust and scalable process [that] results in manufacturing reproducible lots of formulated UsiRNAs with long-term stability," Polisky noted. As such, "we're talking the next logical step and evaluating our proprietary compounds in non-human primates."
These "non-terminal" primate studies, he noted, are designed to give a better indication of the tolerability of the company's formulated RNAi drugs and to provide functional target-knockdown data.
Specifically, MDRNA will evaluate the effect of its UsiRNAs to inhibit Factor VII, an "easily measured target in monkeys," he said. "We're going to be able to get some idea of the tolerance and safety of the material in non-human primates … [as well as] some functional information on the knocking down of a particular gene that is expressed in the liver.
"These are experiments that are designed to broaden our understanding beyond rodents, where we have seen very good behavior of these materials and potent knockdown of the target," he added. "We want to simply determine that we can see the same thing in a non-human primate."
