By Doug Macron
Stealth Biotech has spun out its microRNA-silencing technology into a new company called Mirrx Therapeutics, RNAi News has learned. Concurrent with the move, Mirrx has also secured an undisclosed amount of seed financing that a company official said is expected to enable it to complete planned in vivo proof-of-concept studies.
Stealth was founded in Denmark in late 2007 to develop molecules, dubbed blockmirs, designed to inhibit individual miRNAs (see RNAi News, 1/10/2008). These blockmirs, which are now owned by Mirrx, are steric antisense oligos that bind to specific miRNA binding sites in target RNAs to thereby prevent the small, non-coding RNAs from binding to the same site, according to the new firm.
Importantly, "blockmirs do not recruit any cellular enzymes which mediate degradation of target mRNAs … [so if they do] bind to a non-intended RNA, it will only cause an effect if it prevents binding of a [miRNA] or another cellular factor," an unlikely event, reducing the possibility of off-target effects, the company said.
While Stealth had been developing blockmirs for therapeutic applications, the company also had other activities unrelated to miRNA-targeting therapeutics, Mirrx CSO and founder Thorleif Moller, who also founded Stealth, told RNAi News.
There were venture capital firms that wanted to invest in the blockmir technology, but had no interest in Stealth's other operations, he explained. As such, Stealth established Mirrx, which then received the undisclosed financing from three Danish investment groups: Seed Capital, Inventure Capital, and Vecata Invest.
While the exact amount of the funding has not been publicly disclosed, Moller said that it will "allow us to get in vivo proof of concept in animals for the blockmir concept and keep us going for … two years."
Stealth has already conducted in vitro work demonstrating that the technology "works well," he noted. "What we need to do is [go into] a mouse and see that we can specifically interrupt one microRNA-messenger interaction. We should be able to do that quite soon."
Moller said that the in vivo work will focus on undisclosed targets selected specifically for proof of concept, as well as some related to "areas where we have commercial interest, targets that may have therapeutic relevance."
Noting that much work has already been done examining the role of miR-122 in hepatitis C, including the completion of a phase I study of an miR-122 inhibitor for the disease by Santaris Pharma (see RNAi News, 5/7/2009), he said that one of the areas of interest for Mirrx is hepatitis C.
"For starters, we just want to show that we can block one interaction in vivo," he said. "The problem is that we don't have any easy models for hepatitis C, so we don't get an easy proof of concept for that."
Still, Mirrx has not committed itself to any particular indications just yet, in part because of the newness of the blockmir technology. "We don't have funding to go into therapeutic development, so we're just laying the foundation" for such work, Moller said, adding that the diseases the company ultimately pursues will depend somewhat on the interests of potential partners.
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Meanwhile, Mirrx has been weighing the potential of blockmirs as research tools.
"I would say that blockmirs are probably the best way of validating a microRNA target and messenger RNA because you can directly block the interaction," Moller said. "Normally, you knock out the microRNA and you block the interaction you want to confirm, but you knock out 50 or 100 other interactions. So you may have indirect effects. Moreover, if you want to study the effects of individual interactions in vivo, there is only one way of doing that — using blockmirs."
And, while Stealth had been in negotiations with a tool company about developing and marketing the technology for research applications, Mirrx has put that effort on the backburner in order to focus on its therapeutic activities and completing its proof-of-concept work, he said.
"We will look for partners for the research part later on," he added.
In handing off the blockmirs to a new company solely focused on the technology in order to attract the interest of investors, Stealth is following in the footsteps of two other firms: CytRx and Genesis Research and Development.
An early entrant into the RNAi drugs space, CytRx decided to spin out its activities developing the gene-silencing technology as a drug into a new, pure-play shop in order to give greater visibility to those activities and to better compete with peers in the sector (see RNAi News, 2/16/2006).
Because that spinout, RXi Pharmaceuticals, went public shortly after its establishment in 2007 (see RNAi News, 1/11/2007 & 3/13/2008), it also was able to tap the public markets and benefit from investor interest in RNAi in general.
More recently, Genesis spun out its nascent single-stranded RNAi technology into a new company, called Solirna BioSciences, after its in-house efforts to develop siRNAs as therapeutics ran aground (see RNAi News, 10/29/2009).
According to Genesis, it had been unable to find the funding necessary to continue development of the ssRNAi technology, but attracted the attention of Japanese biotech firm MediBic Group, which agreed to invest in the gene-silencing approach if it could do so without getting involved in Genesis' other activities (see RNAi News, 10/15/2009). The result was the establishment of Solirna.