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Australia's MiReven Moves into Animal Studies as In Vitro Data Nears Publication

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As it awaits the publication of in vitro data from its lead cancer program, Australian microRNA drugs startup MirEven has moved into proof-of-concept animal studies to test various oligo chemistries and delivery technologies, a company executive said this week.

MiReven was founded in 2010 to advance the work of co-founder and Western Australian Institute for Medical Research investigator Peter Leedman on the role of miR-7 in regulating epidermal growth factor receptor signaling in cancer.

EGFR is over-expressed in a number of cancers and is a target for a number of investigational and approved chemotherapeutics, including Bristol-Myers Squibb and Eli Lilly's Erbitux (cetuximab) and Roche/Genentech's Tarceva (erlotinib).

In late 2008, Leedman and colleagues reported that miR-7 down-regulates EGFR mRNA and protein expression in certain cancer cell lines including lung, breast, and glioblastoma, and that the miRNA “attenuated activation of protein kinase B and extracellular signal-regulated kinase 1/2, two critical effectors of EGFR signaling, in different cancer cell lines.”

In light of these and other data, Australian investment group Medical Research Commercialization Fund committed more than $1 million to establish and fund MiReven, which is developing a miR-7 replacement therapy out of Leedman's lab at WAIMR.

The company has more recently generated additional cell-based data demonstrating that the replacement of miR-7 works “synergistically with some of the anti-EGFR drugs, particularly erlotinib,” MiReven Chairman Stephen Thompson told Gene Silencing News.

“What we've seen in vitro is that you can add ... miR-7 and overcome resistance to erlotinib,” he said. Notably, the data also suggest that ordinarily sub-optimal doses of erlotinib become effective when administered with the miRNA mimic.

These findings have been accepted for publication in PLoS One, Thompson said, and are expected to be released “soon.”

In the meantime, MiReven has begun validating these preliminary findings in vivo, and has begun to evaluate different delivery technologies for use with its miR-7 mimics.

In August, the company announced that it had struck a deal to test Silence Therapeutics' suite of lipid-based delivery vehicles (GSN 8/23/2012), and Thompson said that MiReven has a similar arrangement in place with another, undisclosed company.

MiReven is also experimenting with a variety of different modalities for its miR-7 mimic, although it has not settled on which will comprise its eventual drug candidate.

“At the moment, we're using everything that's in the public domain,” Thompson explained, adding that MiReven will likely partner with another company to acquire the rights to its preferred miRNA chemistry since its expertise and intellectual property relates to the biology of miR-7 in cancer.

Thompson noted that it is early days for the miR-7 program and declined to speculate on when a candidate might be ready for human testing. He did note, however, that MiReven has narrowed down its list of probable indications, with head and neck cancer and glioblastoma at the top given the role of EGFR in these diseases.

The company is also considering hepatocellular carcinoma, in large part due to the natural tendency of oligonucleotides to aggregate in the liver.

He also said that while MiReven is testing the effects of miR-7 replacement therapy on its own, the firm is also very interested in exploring its use in conjunction with existing therapies like Tarceva.

“These days, very few people try to develop a novel chemotherapeutic as a standalone, particularly if there is a rationale for it being synergistic [with] or overcoming resistance to another class of drugs that you know is working in the same pathway,” Thompson noted.

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