Drug Development

AstraZeneca and Moderna take a big, early step forward in their quest to prove mRNA works in humans

Mene Pangalos, AstraZeneca

Biotech unicorn Moderna has revamped its development structure, pulled back the veil on more of its R&D work and spotlighted a significant clinical step forward for one of its most advanced — though still very early-stage — messenger RNA therapies in the pipeline.

Tackling the very ambitious work of regenerating cardio tissue — long one of the Holy Grails in stem cell therapy — Moderna’s close partners at AstraZeneca say they got the safety and efficacy data they were looking for on AZD-8601 in Phase I. Working with a biomarker at this stage, investigators tracked expression of VEGF-A protein in the skin — giving them some early confidence that a technology initially developed at Harvard had some real proof-of-mechanism evidence to back it up with. That in turn has inspired AstraZeneca to take the next step on the messenger RNA front as it journeys into Phase II, where they will look for more solid evidence of its regenerative powers among patients undergoing coronary artery bypass grafting.

The first clinical snapshot, says Moderna CFO Lorence Kim, “looks like a local, transient surge of growth factor,” which is what the biotech and its Big Pharma partner was looking for in trying to achieve in a targeted way what systemic stem cell treatments failed so spectacularly at.

Regenerating tissue presents some huge challenges to researchers, along with the potential for some huge rewards. That’s what inspired AstraZeneca CEO Pascal Soriot to buy into Moderna for hundreds of millions of dollars.

“I think we’ve made great progress,” Mene Pangalos, an executive vice president at AstraZeneca, tells me. Building on “really cool preclinical data on wound healing,” investigators will now see if they can use this technology to “restore function to the heart.”

The focus on clinical development at Moderna now — after spending several years stealthily working on its preclinical programs — includes mRNA-2416, a new OX40L immunotherapy that will set out to try a brand new approach in I/O. And it’s looking to spur liver expression of therapeutic proteins with mRNA-3704, for methylmalonic acidemia (MMA), a lethal rare liver disease.

Stéphane Bancel

Early on, Moderna set up 5 subsidiary asset vehicles for its programs. But now CEO Stephane Bancel and the board are opting to strip the compartments down, pooling their 16 announced programs into a single pipeline that will offer a quick snapshot of how its building new therapeutics on the mRNA platform that they’ve built.

Research/preclinical development will report to Moderna President Stephen Hoge, while clinical development will operate under Tal Zaks, Moderna’s Chief Medical Officer. R&D teams will be “aligned around three core matrixed therapeutic areas — infectious diseases, immuno-oncology and rare liver diseases.”

This way, Bancel explains, execs can encourage better line of sight across all the work being done at a company that has swelled to 550 staffers, while adding some ambitious building plans to prep for the manufacturing work that needs to be done.

STAT has been hammering Moderna repeatedly for a slate of supposed shortcomings at the Cambridge, MA-based trendsetter. Attracted by the biotech’s rep for a multibillion-dollar valuation very early on, along with a stealthy approach to R&D, the online healthcare news pub has sought to poke holes in the story wherever it can.

Step by step, though, Moderna has been opening up both externally and internally, revealing some wildly ambitious science, the first steps in human studies and a maze of daunting tech challenges they’ll need to overcome in the long quest to achieve new drug approvals.

The biotech has a long way to go, but now it wants you to know more about where it plans to get to.


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