Secretive Moderna Shakes Up R&D Model, Shows Off Early-Stage Trial Data

Published: Sep 15, 2017

Secretive Moderna Shakes Up R&D Model, Shows Off Early-Stage Trial Data September 14, 2017
By Mark Terry, Breaking News Staff

Cambridge, Mass. – The often secretive Moderna Therapeutics released information about its clinical programs as well as new information regarding new development candidates.

• The company has wrapped up a Phase I trial of mRNA AZD-8601, the first-ever mRNA therapeutic to be evaluated in the clinic. It is expected to move into Phase II. It is under development with AstraZeneca to express a local and transient surge of vascular endothelial growth factor-A (VEGF-A) in cardiovascular diseases. The first study was in male patients with Type 2 diabetes mellitus, where it met its primary endpoint of safety and tolerability, and also showed proof of mechanism.

AstraZeneca submitted a Clinical Trial Application (CTA) in Europe to start a Phase IIa trial of the drug in heart failure patients undergoing coronary artery bypass grafting (CABG) surgery.

• Moderna also started a Phase I trial of mRNA-2416, an intratumoral (iTu) immuno-oncology (IO) drug that has the potential to improve T-cell attack against tumors.

• In addition, Moderna reported its first clinical development candidate that uses liver expression of therapeutic proteins, a new modality. It hopes to advance the product, mRNA-3704, toward the clinic for methylmalonic acidemia (MMA), a serious and life-threatening rare liver disease. There are currently no approved therapies for MMA.

• Moderna also announced four new development candidates to its pipeline. It has replaced its preclinical stage Zika vaccine DC, mRNA-1706, with mRNA-1893, a Zika vaccine that uses an enhanced mRNA construct that it hopes will have improved immunogenicity.

All told, Moderna has 16 mRNA therapeutics and vaccines in its pipeline. They vary across infectious diseases, cancer immuno-oncology, cardiovascular diseases and rare liver diseases. In seven mRNA clinical trials, 460 patients have been dosed.

“2017 is a major inflection point for Moderna, as we’ve made significant progress advancing mRNA therapeutics for unmet needs across several disease areas,” said Stephane Bancel, Moderna’s chief executive officer, in a statement. “In the cardiovascular space, our partner AstraZeneca successfully completed a Phase I study for mRNA-AZD-8601, a VEGF-A therapeutic, and planning is underway for a Phase IIa study. In addition, we have initiated first-in-human dosing in a Phase I study of mRNA-2416, our first immuno-oncology candidate, encoding OX40 ligand. We also have progressed the expression of therapeutic proteins in the liver as a development stage modality. As such, we are now able to advance chronically dosed mRNA therapeutics to development for rare liver diseases. I’m very thankful to the Moderna team for their commitment, dedication and continues progress to deliver on our mission.”

Moderna has been involved in a a lengthy legal battle with Arbutus Biopharma over its mRNA delivery system.

“We have seen no evidence of a Moderna delivery system that is free of our intellectual property,” said Mark Murray, the chief executive officer of Arbutus, to Forbes in May. “Not in their publications, their presentations, or in the examples in their patent filings. In our view what they are reporting as theirs appears to be dominated by our intellectual property.”

Arbutus is in a legal battle with a smaller company that partnered with Moderna. Bancel, for his part, has brushed off the claims of Arbutus, saying that the technology was never very good and the company had gone on to develop its own delivery system. Forbes, however, writes, “There’s no denying that Moderna, for all the hype, had to rely on Arbutus’ technology to get its efforts off the ground.”

Moderna’s overall technology is to deliver therapeutics to messenger RNA, which tells cells what proteins to manufacture. In other words, the therapeutic delivers a new code and the body does all the work churning out whatever drug it’s being instructed to make. But the trick is getting mRNA into the body’s cells. Typically, Moderna has used lipid nanoparticles (LNPs). And four times Moderna licensed LNP technology from a Vancouver, British Columbia company called Acuitas, which largely operates out of its owner’s garage. Acuitas had a license from Arbutus as part of a previous legal settlement.

In 2016, Arbutus terminated Acuitas’ license to the tech and stated it didn’t have the right to sublicense the delivery system to Moderna. In February 2017, a judge in British Columbia issued an injunction that kept Acuitas from further sublicensing the delivery system until trial.

In March 2017, Alexion paid Arbutus $7.5 million and $75 million in possible future payments for LNP technology for one drug it is developing with Moderna. Arbutus also won royalties and $65 million in payments from Alnylam in 2012 over its technology.

The cases involving Acuitas, Arbutus and Moderna are still pending.

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