Can RNA editing take Atlas startup where Vertex couldn't go? Korro lands $116M to find out
As the CEO of RNA editing startup Korro Bio, Ram Aiyar often gets the same question.
“I get always asked, you know, if you can fix DNA, why bother with RNA?” he told Endpoints News. “And it’s like asking, which child do you prefer — your older one or your younger one?”
But investors are appreciating the difference. More than a year after closing its Series A just shy of the megaround mark, Korro Bio is back in the spotlight with $116 million in fresh cash and a lead candidate — targeting alpha-1 antitrypsin deficiency, or AATD.
Whereas gene editing on the DNA level promises a one-and-done approach to genetic disorders compared to the traditional approach of blocking problematic proteins, RNA editing occupies a space somewhere in between: a transient yet precise fix that gets to the root of a disease.
And unlike the other RNA modalities, from antisense oligonucleotides to RNA interference, Korro is not interested in knocking down production of pathogenic proteins.
Inspired by a natural mechanism in squid and octopus, the biotech’s scientists use oligonucleotide guides to recruit an endogenous enzyme known as ADAR to a specific RNA site where they want to convert an A to a G — the kind of change that can make a world of difference for disorders like Rett syndrome, co-founder and chairman Nessan Bermingham previously noted.
“All the targets that we look at, we’re looking at it from a gain of function standpoint,” Aiyar said. “So either increasing the half life of a protein, or upregulating the protein, or repairing the protein that is at a low level, is really going to be the focus. It’s a modality that only small molecules currently really play in, but they haven’t been able to do that successfully because they’re not highly specific.”
Aiyar believes those unique characteristics would allow Korro to target prevalent indications, setting them apart from peers like Shape Therapeutics, which he notes is focusing on permanent editing. And AATD, with somewhere between 100,000 and 150,000 patients, is just one of them.
First brought onto the broader biotech stage by Vertex, AATD is marked by misfolded proteins that go from the liver to the lung. Vertex tried to fix it by binding to the protein in a way that it believes is responsible for the misfolding, but culled its initial small molecule candidates after deciding they’re unlikely to show clinical benefit.
“It’s a very, very differentiated program relative to small molecule correctors because they’re just sitting in the pocket and trying to prevent the misfolding, whereas we are fixing the amino acid sequence on the RNA side to ensure proper folding,” Aiyar said.
Delivery, he reckons, will be the main challenge here. But since Korro is working with mechanisms like GalNAc and LNPs, Aiyar notes that “we are standing on shoulders of giants” like Alnylam and Ionis.
Eventide Asset Management led the Series B, with participation from new investors Fidelity Management & Research Company, Invus, Point72, Verition Fund Management, Monashee Investment Management, Sixty Degree Capital and an additional healthcare specialist fund. All existing investors joined, bringing to the syndicate Atlas Venture, NEA, Wu Capital, Qiming Venture Partners USA, Surveyor Capital (a Citadel company), Cormorant Asset Management, MP Healthcare Venture Management and Alexandria Venture Investments.
Having grown the team from 27 to 59 in just around eight months, Aiyar expects the funding to fuel a continued hiring drive so Korro has enough staffers to construct a sizable pipeline. They’re developing a CNS program to balance out the lead liver indication, with other chronic indications in mind, before getting into the clinic, ideally in the next 18 months.
“The biology here is very novel,” he said. “I think it’s going to be hard for people to dabble rather than, you know, take a very concerted effort in terms of clinical development, because the last thing you want to do is get to the clinic with a compound that looks good and then fall off the cliff very fast.”