By Doug Macron
Having just acquired the diagnostic rights to RiboTask's unlocked nucleobase analog technology, MDRNA has taken another step toward broadening its reach beyond RNAi-based therapeutics, and potentially into companion diagnostics and microRNA-targeting drugs.
And while the company is keeping its focus on its pipeline of siRNA therapeutics in the near term, with access to UNAs and other technologies, "we've established the intellectual property portfolio and basis to be an integrated personalized medicine company focused in nucleic acid therapeutics and diagnostics," President and CEO Michael French told Gene Silencing News.
This week, MDRNA announced that it had licensed the exclusive rights to develop, make, use, and sell diagnostics based on RiboTask's UNA technology, which comprises an acyclic ribonucleoside analog in which the bond between C2' and C3' atoms is broken. The resultant change in sugar structure is designed to make the analog flexible and reduce the binding affinity of an siRNA's strands.
In 2008, MDRNA picked up the therapeutic rights to the technology under a deal that was later amended to eliminate certain payments to RiboTask (GSN 10/23/2008 & 6/25/2009).
According to French, having these rights to the UNA technology complements the company's existing therapeutic and diagnostic rights to what it calls conformationally restricted nucleotide technology.
CRNs, which were called bridged nucleic acids by their developer Valeant Pharmaceuticals, are essentially "novel nucleoside analogs in which the flexible ribose sugar is locked into a rigid conformation by a small chemical linker. When included in single- or double-stranded oligonucleotides, the highly stable A-form of RNA or DNA is favored, resulting in increased thermal stability of a duplex or higher affinity of a single strand for its complementary target," according to MDRNA.
MDRNA acquired the IP estate covering BNAs from Valeant in March (GSN 3/25/2010).
"The CRN technology … basically provides us with what we believe are the same capabilities that are inherent in the locked nucleic acid technology — the ability to provide stable forms of double-stranded or … single-stranded oligonucleotides," French explained.
UNAs, on the other hand, provide a "more flexible structure," he said. When applied to therapeutic molecules such as siRNAs, "those two technologies [can impart] different kinds of characteristics."
However, the two technologies also can be used to develop molecular probes for diagnostics, an area into which MDRNA is considering expanding, French noted.
At this stage of the game, however, "we're kind of just scratching the surface of the whole diagnostic play and looking to how we can best leverage and monetize that in a major way," he stressed. "We see the potential, but how we specifically exploit that potential" has yet to be determined.
French said that MDRNA plans to hire consultants to help it decide whether a diagnostics play "is something we do ourselves, spin out, joint venture, or simply license."
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Regardless of how it pursues diagnostics development, MDRNA intends to ensure that it has the ability to develop companion diagnostics for its own drugs.
"We have some initial thoughts that we might be able to develop UsiRNAs that target a particular mutant," French said. "If that's the case, if we can use UNAs and the CRN technology to develop a UsiRNA that targets a specific mutant or specific SNP in some sequence, then we have to have the companion diagnostic to identify that.
"For us, no matter how we leverage and monetize this capability, we want to make sure we're maintaining [an] opportunity for us to develop companion diagnostics for our products," he said.
At the same time, MDRNA is also evaluating other therapeutic avenues for which the UNA and CRN technology would have potential, including miRNA-targeting drugs, French noted.
Applied to single-stranded oligos, the CRN technology becomes a sort of second-generation antisense approach and gives MDRNA the capability to down-regulate miRNAs, he said.
Given big pharma's interest in the non-coding RNAs as targets, such as GlaxoSmithKline's deals with Regulus Therapeutics (GSN 2/25/2010), "clearly, there is interest in the second-generation antisense approach [and] microRNAs." As such, this is an area MDRNA is strongly considering.
Notably, last month MDRNA announced that it would be working with an undisclosed company on developing miRNA-directed cancer drugs using its proprietary DiLA2 delivery technology (GSN 5/6/2010).
MDRNA isn't likely to unveil an miRNA program in the next few months, however, but "we may, as we move forward, look at bringing in through licensing or other transactions microRNA targets," French said.
"Fundamentally, we have the intellectual property basis for developing a business along the lines of Regulus, Santaris [Pharmaceuticals], and Exiqon," he added. "It takes a tremendous amount of expertise and capital to achieve that, but we've got the fundamental expertise and now the intellectual property portfolio to do it."
As of right now, however, MDRNA is keeping its eye on its near-term initiatives, including its bladder cancer program, which is expected to yield an investigational new drug application before the end of the year, and the pending acquisition of Cequent Pharmaceuticals, which has its own drug candidate poised to enter the clinic (GSN 4/8/2010), he said.