Skip to main content
Premium Trial:

Request an Annual Quote

Mirna Becomes First to Advance Therapeutic microRNA Mimic into Human Testing


Three months after releasing preclinical data on its microRNA replacement cancer therapy MRX34, Mirna Therapeutics has begun recruiting patients in a phase I trial of the drug, a company official said this week.

Although a number of other companies are developing drugs that antagonize specific miRNAs, Mirna is focused primarily on miRNA mimics. With the start of the MRX34 trial, the company is the first to move such a molecule into human testing.

One other company, Santaris Pharma, has an miRNA drug in the clinic. However, that agent — phase II hepatitis C treatment miravirsen — is a locked nucleic acid inhibitor of miR-122.

MRX34 is a synthetic version of miR-34a, an miRNA known to play a key role in the p53 tumor-suppressor pathway. Mirna has also said that its own work indicates that miR-34a represses the expression of more than 20 oncogenes and inhibits processes required for cancer cell viability, cancer stemness, metastasis, and chemoresistance.

The drug, which is formulated with Marina Biotech’s Smarticle liposomal delivery technology, has also been shown to significantly inhibit liver tumor growth and reduce lung tumor burden in mouse models.

Mirna President and CEO Paul Lammers called the start of the phase I trial an “exciting” development for the cancer community, with researchers expressing interest in controlling “multiple oncogenic pathways at the same time with one microRNA.

“We’re very excited and … there is huge interest in microRNAs as a new potential therapeutic approach in cancer,” he told Gene Silencing News this week.

The two-part phase I study will enroll patients with primary liver cancer or advanced metastatic cancer, including lymphoma, with liver involvement.

In the first part of the trial, around 30 patients will receive escalating doses of MRX34. Once the maximum tolerated dose is reached, an additional 18 patients with select cancers will be enrolled for a dose-enrichment phase designed to test the drug’s efficacy outside of the liver.

“We know that lipid-based formulations have the tendency to go to the liver — that’s no secret,” he said. “However, we see some very interesting biodistribution with MRX34 to other tissues.”

For instance, Mirna’s data suggest miR-34a is highly involved in non-small cell lung cancer, and Lammers previously said if the company is able to deliver enough of its miRNA mimic into lung tumors, it may enroll additional lung cancer patients — even those without liver metastases — into the enrichment phase of the study.

“As one of our scientific advisors said, ‘You might be surprised what you see with a drug like MRX34,’” he noted this week.

Determination of the maximum tolerated dose of MRX34 and the identification of dose-limiting toxicities are the primary outcome measures of phase I trial, although peak plasma concentration and area under the curve of the drug, as well as evidence of clinical activity, will also be evaluated.

The dose-escalation phase of the trial is expected to take around a year, with another six months or so to complete the enrichment phase.

As the study is proceeding, Mirna is also working with MRX34 to identify other possible indications for which it might be used and to explore the possibility of its combination with other cancer treatments, Lammer said.

“We’re doing a lot of additional in vivo work in-house [with orthotopic cancer models] and with some leading academic centers … to [find out] what other types of tumors we could target with MRX34,” he said. “It could be anything from lung to pancreatic to glioblastioma. There are a lot of things we’re focusing on.”

At the same time, “we’re doing a lot of work to supplement the potential application [of MRX34] in combination with chemo or untargeted therapies or radiation therapy, for that matter,” Lammers said.

The company also continues to advance its preclinical pipeline, which includes mimics of let-7, miR-16, and other undisclosed miRNAs. However, Lammers stressed that MRX34 remains Mirna’s top priority.

The other drug candidates, he said, “are all very interesting from a pharmacology profile point of view, and they all deserve ultimately to go to the clinic. But right now MRX34 is our key focus.”

Marina’s Mirna Milestone

Although Mirna obviously has the most to gain from the phase I trial of MRX34, struggling RNAi drug firm Marina Biotech may also end up benefitting.

In early 2012, Marina licensed its Smarticle technology to Mirna for use with the drug candidate in exchange for as much as $63 million in upfront fees and milestones. While the specifics of the arrangement were not announced, Marina President and CEO Michael French previously told Gene Silencing News that the initiation of clinical testing of MRX34 would trigger an undisclosed milestone payment.

Marina has been struggling for some time under a severe cash crunch, and in mid-2012 the firm was forced to shut down virtually all of its operations (GSN 6/7/2012).

About a year later, the company disclosed that it had defaulted on repaying outstanding secured indebtedness as it faced the prospect of bankruptcy (GSN 1/31/2013).

Officials from Marina did not return a request for comment on the impact of any milestone related to the MRX34 study.