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Arcturus Demonstrates mRNA Delivery to Primates, Sees Possible Rx by 2016

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NEW YORK (GenomeWeb) – Arcturus Therapeutics this week released data showing that its lipid nanoparticle technology, dubbed Lunar, can deliver messenger RNA into non-human primates, triggering significant production of a therapeutic protein after a single dose.

Based on these and rodent data demonstrating mRNA delivery to the liver, lung, muscle, and tumor tissue, Arcturus is now working on identifying promising indications for the technology, with an eye to initiating Phase I testing of an mRNA drug as early as 2016.

Arcturus was founded in mid-2013 to develop RNAi therapeutics based on the Lunar nanoparticles, which are promoted as offering a higher therapeutic index than other lipid nanoparticles due to their biodegradability, and unlocked nucleobase analog-modified siRNAs.

The company has since named two lead candidates, the transthyretin-mediated amyloidosis treatments LUNAR-101 and LUNAR-102. The first is under development for a manifestation of the disease called familial amyloidotic cardiomyopathy and the second for a version called familial amyloidotic polyneuropathy.

These two drugs remain the company's top priority and are on track to move into Phase I testing in early 2015 and 2016, respectively. However, the company has been actively investigating whether Lunar could also be used with other RNA medicines.

In early 2014, the company presented data showing that it could deliver and express luciferase mRNA in the livers of mice. This week, it unveiled additional data extending that work in rodents and, more importantly, non-human primates (NHPs).

Specifically, Arcturus showed that intravenous administration to NHPs of synthetic human erythropoietin (EPO) mRNA using Lunar nanoparticles led to the production of 42 ng/mL of EPO protein — representing a 1,000-fold increase over normal levels in man — after a single .3 mg/kg dose. Additionally, the EPO levels remained elevated up to 24 hours after treatment.

No safety issues were observed in any of the animals tested, according to the company.

In rodents, Arcturus showed that Lunar could deliver luciferase mRNA into the lungs and livers of mice as well as tumors with the inclusion of a targeting technology after intravenous administration. The company was also able to demonstrate functional delivery of mRNA into mice with intramuscular administration.

Buoyed by these findings, the company has become increasingly bullish about its potential in the burgeoning mRNA therapeutics space, Arcturus CSO and COO Pad Chivukula told Gene Silencing News. And while it remains interested in exploring partnerships in the field, the firm is also considering advancing an mRNA program into the clinic on its own.

"We think that we can potentially take one of these drugs into the clinic," possibly in 2016, he said. Doing so, however, will require serious consideration of what indication makes the most sense for such a new therapeutic modality.

"This is a completely new field, there have been no [investigational new drug applications] ever … so we're treading cautiously," Chivukula said. At this point, however, the company sees promise in cancer and cystic fibrosis.

To that end, it has generated in vitro data showing that human cells can be transfected with mRNA for the tumor suppressor p53 and cystic fibrosis transmembrane conductance regulator, which is implicated in cystic fibrosis.

Arcturus also sees the potential of joining its mRNA and RNAi technologies into a single product, Chivukula said. Using cancer as an example, he pointed to the possibility of using siRNAs to knock down an oncogene and mRNA to express a protein that induces apoptosis in tumors.

However, he stressed that this work remains very early stage.

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