A gene editing 3.0 player goes deep on cash, frontier science to put precision epigenetics to the big test

Bioregnum Opinion Column by John Carroll

Issi Rozen is as deeply embedded into the gene editing field as anyone in the buzzy Cambridge, MA biotech hub. As chief business officer and strategy chief for the Broad over a decade-long stretch, he’d worked with all the big names in a scientific discipline that promises to upend the therapeutics field — eventually. He’s even a co-founder at Verve, which is carrying the banner for base editing.

So it was a bit surprising to hear the GV venture partner say that when it came to the B round for Chroma Medicine, he made the call to ask to get in on the new, $135 million raise for the epigenetic editing biotech that goes public today.

On the other hand, going back to the first time Rozen heard about epigenetic editing, his first reaction was:

“I couldn’t figure out how they’re going to do it. I said, ‘Well, how is it going to work exactly? What are you going to do? How are you going to change it?’ And people like Keith Joung, who’s also a co-founder — and Keith and I go back many, many years — Keith’s actual initial interest in technology was epigenetic editing, not DNA editing, which I learned more recently, because I’ve known him from Editas and Verve and from other editing companies. But when I talked to him, he said, ‘I really got into this because I really wanted to do epigenetic editing when I got started in this field.’”

Roll forward to 2023, and Rozen ended up leading the round on this go, which follows the big $125 million A round splash Chroma made during the go-go months of 2021. Unlike many of the 2021 class of upstarts, though, Chroma is still getting the big money to match its oversized ambitions in the field.

Where CRISPR and base and prime editing involve chopping and changing DNA, spurring intense speculation about off-target effects and a range of safety concerns that the pioneers are still grappling with, precision epigenetic editing is all about using an endogenous system to control gene expression, without making any changes to DNA.

Think of it as the Volvo of gene-editing programs, built for safety and fine-tuned control of gene expression. But very much still on the drawing board.

It’s the kind of technology that is particularly suited for diseases that involve more than one gene, says Rozen, where you need to limit the potential consequences of multiplexing.

The CSO at Chroma, Vic Myer — who worked for nearly five years at Editas, one of the original gene editing players — recalls his first look, as he and the CEO, Catherine Stehman-Breen, were brought in to kick the tires and check out the scientific work.

“I think it had a lot of promise to be super, super-efficient,” recalls Myer. “And I think one of the things that helped us with this fundraise … is we have some data that we’re going to be presenting at upcoming scientific conferences that shows really, really striking in vivo data that’s super-efficient at two different targets in two different systems. And so that’s coming.”

The data, along with all the info on the targets and so on, are all still preclinical. Like the other gene editing technologies, Chroma’s 80-plus team has to steer through mouse studies, then prove themselves in non-human primates and go on to live up to the notion that they have a practical approach to try in humans.

Myer’s personal path to Chroma took him through an entrepreneur-in-residence program at Atlas Venture, which played a big part in setting up the ambitious startup.

The scientific founders include some star names, including the Broad’s David Liu, Mass General’s Joung, MIT’s Jonathan Weissman — all present at the creation of gene editing. UCSF’s Luke Gilbert and Angelo Lombardo, who worked alongside the noted gene therapy scientist and Chroma scientific founder Luigi Naldini at the San Raffaele Telethon Institute for Gene Therapy, completed much of the seminal scientific work around epigenetic editing.

But they all played a part. And while the Chroma team isn’t being too specific on plans for going into humans, they all know it can’t be indefinite.

“I think if you talked to David, or Keith, or Jonathan, they’d say the time was right,” says Stehman-Breen about the launch. “The technology had matured enough. I would say the first generation was actually Angelo’s technology, that hit-and-run technology that was a little clunky but incredibly promising. It was built upon by Jonathan and Luke to make the single construct that allowed Vic to rather quickly validate the technology and then improve upon that technology so that it could ultimately be used effectively in humans.”

Over the past 10 years, we’ve seen a number of new tech waves take shape in biotech, each usually promising to dominate the sea of drug opportunities in front. But gene editing is different. Here, the new companies like Chroma are promising to carve out a section of the therapeutic panorama for itself, leaving the early players to battle it out in their own respective domains. Founders who jumped to the latest developments are still on the advisory boards of gene editing 1.0, or 2.0.

“It’s exciting,” says Rozen, “because as we don’t have one small molecule company or one antibody company. I think in editing we’ll see the same thing. We’ll have different companies developing different therapeutics for different conditions and using different technologies, which, hopefully, will be fantastic for patients.”

And like everything that attracts investors, you can bet that there will be plenty of competition. Epigenetic editing has quickly spawned a rival set of biotechs, with more likely in stealth.

Atlas is sticking with the syndicate, joining the B round with some noted investors who like to swing for the fences. That group includes ARCH — where Bob Nelsen is a big believer in all things Liu — Mubadala, Alexandria Venture Investments and a number of others.

Along the way the executive team and board has been under steady construction, drawing in Spark founder Jeffrey Marrazzo to the board.

Now they’ve got the money to see if they can do something big — or not.

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gene therapy
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