UPDATED: Amit Munshi has more than $300M and a startup CSO out to pioneer next-gen RNA therapeutics. Once again, he’s thinking big

Bioregnum Opinion Column by John Carroll

Amit Munshi had to beg off when he was first introduced to the idea of running an MPM BioImpact stealth player named ReNAgade Therapeutics. He had just sold Arena to Pfizer for $6.7 billion — a deal that wrapped in the spring of last year — after getting a lot of credit for turning the biotech around. And he was a hot commodity.

But first, before jumping back into the biotech forge of making new drugs, Munshi tells me, he wanted to spend some time with his aging parents in Houston, and his wife had the same idea, which took them to Bangkok. Munshi calls it all part of life’s deferred maintenance.

Then he jumped in at the helm officially about a month ago, after earlier joining the board.

Today, he and his CSO, Pete Smith, who’s labored on first-gen RNA therapeutics for Moderna and Alnylam, are having a coming-out party for a company first hatched 18 months ago. And they are employing every buzzy phrase you can imagine – from “unlocking the limitless potential of RNA” to orchestrating a suite of technologies for delivery — starting with more advanced lipid nanoparticles to “coding, editing and gene insertion tools.” They are shooting to use their delivery tech to achieve “the potential to treat any disease anywhere in the body.”

Pete Smith

Outside the liver, one of the holy grails of RNA work.

But Smith and Munshi say they’ve done a lot more than assemble some hot PR in the last few months. There’s a team of more than 100 already in place. There are some very specific ideas about overcoming the kind of challenges that a bevy of leaders in the space — think Moderna and BioNTech, for starters — have been hammering at. They’ve already quietly joined a tri-party, multibillion-dollar alliance with Orna, another MPM startup looking to make waves with circular RNA, and global giant Merck, which put up $250 million in cash last year to get things rolling.

And, they add, there are some advanced preclinical proof-of-concept data they’re working with from non-human primates, where Munshi says they’ve been able to deliver LNPs to other places than the liver, which absorbs material like a sponge.

“We’re really mindful of not coming out of stealth before we were on solid footing,” says the re-minted biotech CEO. “So, coming out of stealth with a lot of promises as opposed to coming out with a lot of science, though, we really prefer to let the science lead.”

Smith spent the last 10 years in the RNA mines, digging for data. He’s intimately familiar with the groundbreaking LNP work that MIT’s Bob Langer helped create. After counting himself as roughly employee #30 at Moderna, he worked on MC3, the first “test lipid” in play at Moderna. He did early work developing the lipid that went into the hugely successful pioneer Covid vaccine. And he took that work on lipids forward at Alnylam as it rushed to commercialize its first five drugs.

Ansbert Gadicke

Those experiences have helped Smith recruit a large team of scientists who have been at the forefront of the RNA push, working on extrahepatic delivery and “how you differentiate one lipid nanoparticle from another, whether it’s the ionizable lipid or whether it’s the formulation that you make. And through that combination, we have a high-throughput screen, both in mice and in monkeys. It’s allowed us to really understand the biodistribution of different lipid nanoparticles.”

And from that, they’ve been learning how to “interact specifically with a particular cell type at the level of the cell membrane.”

That race to test the tech in humans is already well underway, says Munshi. This means that the $300 million-plus raised from an investor group led by MPM BioImpact’s Ansbert Gadicke — who played a big role in this — and F2 is earmarked for a marathon tech run.

Tom Barnes

“If we’re going to make progress fast, you can’t increment your organization, your team,” says Munshi. “You need critical mass. You need to be able to do high-throughput activities. You need to be able to get lipid nanoparticle conjugates. You need to start parallel processing the ability to carry payloads on the editing side.”

All roads in Boston biotech lead back to Millennium, as any weathered vet will tell you. So it’s no wonder that Smith and Orna CEO Tom Barnes — another Millennium alum — go way, way back. It’s just one of many connections that helped shape the company and set the stage for an alliance with a biotech startup that has its own dreams of taking mRNA into the next chapter.

“As ReNAgade was coming together in the early days, I remember Ansbert asked me, ‘Hey, do you know Pete Smith?’ I said, ‘Pete Smith, he’d be great,’ Barnes tells me. So Smith left Alnylam to join” MPM as an executive partner. “It was kind of like a reunion.”

Barnes hasn’t been disappointed.

“You tell me where you can deliver, and I’ll tell you the diseases you can cure because everything else is just dreaming,” Barnes adds. “RNA can do this, and RNA can do that. Right, but you have to get there. If you can’t get there, you can’t do anything.”

They chose a limited number of high-value areas for ReNAgade to work on lipid discovery. “And we decided to throw vaccines in there” because there was a bit of a cavalier attitude about lipids for vaccines that are jammed straight into the muscle.

“ReNAgade in short order delivered quite well on the vaccine side,” and Barnes is hopeful they can keep on innovating. And they’ve demonstrated their progress in preclinical work. “They’ve been doing the heavy lift of screening them in vivo, which is what you need to do.”

But circular is just one of many RNA types that ReNAgade is working with, notes Munshi, pointing to “lines, circles, short RNA…the whole gamut” as they explore where to go. And that includes some proprietary work that’s still under seal.

For now.

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