Feng Zhang’s quiet spinout snares $215M in a race for the next big CRISPR company
After Sigilon Therapeutics’ $126 million IPO last December, COO Devyn Smith started getting calls. Job offers, mostly, for this biotech or that, none that quite hit.
Then a recruiter reached out about an opening at a spinout from Feng Zhang’s MIT CRISPR lab that, despite a flashy launch, had gone largely quiet for three years. The company, Arbor Biotechnologies, was ready to enter a new phase and needed a new leader with experience bringing drugs into human trials. Smith, a former Pfizer executive remembering the press releases around Arbor’s launch, said yes.
Nearly a year later, Arbor is quiet no longer. Four months after Smith officially joined as CEO, the biotech announced a $1.2 billion deal with Vertex to help the big biotech develop to engineer pancreas cells that can be transplanted into a diabetes patient without triggering an immune response, among other cell therapies.
And on Tuesday, the company announced new a bit of cash: $215 million in Series B funding — more than 13 times the Series A — led by Temasek, Ally Bridge Group, and TCG Crossover.
The Steph Curry-sized deal will bankroll Arbor’s transition from a biotech focused solely on mining the microbial world for new CRISPR-based gene editing tools to a biotech that tries to turn these new tools into medicines.
In doing so, it joins a small flurry of biotechs claiming they can expand gene editing’s reach by relying on newly discovered DNA-cutting enzymes: not just the Nobel-winning Cas9, but also Cas12, Cas13, CasX, CasΦ and a long list of more obscure genetic blades.
These companies tout either their exceptional ability to engineer enzymes (Scribe), or their exceptional ability to sift for new enzymes among large databases of bacterial genomes (Metagenomi), or both (Arbor). Often, they make dueling claims in the press. Mammoth, in announcing a $195 million round to finance its own expansion into therapies, claimed to have “the largest toolbox of novel Cas enzymes.” Arbor on Tuesday said it had “the most extensive toolbox of proprietary genomic editors in the industry.”
None of these companies are yet near the clinic, but larger drugmakers are watching closely. Despite a long-running collaboration with CRISPR Therapeutics, Vertex struck deals the past year with both Mammoth and Arbor to find enzymes that fit the new therapies they’re developing. Moderna turned to Metagenomi for the mRNA behemoth’s first foray into gene editing, disappointing investors who hoped Moderna would strike a larger deal with one of the original CRISPR companies.
Smith notes Arbor, founded in 2016, has been working on new enzymes longer than its rivals. He has spent much of his first year at the company helping craft a strategy to move those enzymes into the clinic.
The company will start in the liver, he said. It’s easier to deliver CRISPR there than any part of the body, as Intellia did with lipid nanoparticles earlier this year. But Intellia only knocked out a single gene. Smith said Arbor will try to use new and more versatile enzymes to do what he called “knockout-plus”: either knocking out a gene and inserting a new one, or knocking out multiple genes.
“It allows us to really see how we differentiate from some of the simple knockdown approaches the Cas9 folks are taking,” Smith said. It “demonstrates the utility and functionality of our editors.”
Inserting genes has proven one of the biggest hurdles in CRISPR gene editing, because it relies on human cells’ own intricate and difficult-to-manipulate DNA repair mechanisms. Conversely, researchers fear that making multiple cuts to the genome at once, at least with current editors, can lead to off-target effects and other forms of DNA damage.
Then Arbor will try to edit the central nervous system. That’s “an area where we feel there’s really an opportunity to differentiate significantly and be first in class in that space,” Smith said.
Although companies, including Arbor, are developing alternative delivery technologies, putting CRISPR in the central nervous system requires strapping it into an adeno-associated virus, the harmless virus commonly used across gene therapy.
Most CRISPR systems are too big to fit inside these viruses, so smaller editors could offer a significant advantage.
CRISPR systems can also only edit parts of the genome that happen to be near a genetic landing strip called a PAM site, limiting the number of genes and diseases you can target. Smith said the company developed editors that can hit a broader range of targets.
The goal is to file for FDA clearance for Arbor’s first trial by the end of 2023. In the meantime, they’ll continue expanding, spending the company’s newfound galleons on doubling their staff from around 60 employees to around 120.