As CEO of RNA publishing startup Korro Bio, Ram Aiyar often asks himself the same question.
“I always get asked, you know, if you can fix DNA, why bother with RNA? ” he said Terminal news. “And it’s like asking, which child do you prefer – your oldest or your youngest?”
But investors appreciate the difference. More than a year after its Series A closed just below the mega-towers mark, Korro Bio is back in the spotlight with $ 116 million in fresh cash and a lead contender – targeting alpha deficit. 1 antitrypsin, or AATD.
While gene editing at the DNA level promises a unique approach to genetic disorders compared to the traditional approach of blocking problematic proteins, RNA editing occupies a space somewhere in between: a transitory but precise solution which goes to the root of a disease.
And unlike other RNA modalities, from antisense oligonucleotides to RNA interference, Korro is not interested in suppressing the production of pathogenic proteins.
Inspired by a natural mechanism in squid and octopus, biotechnology scientists use oligonucleotide guides to recruit an endogenous enzyme known as ADAR to a specific RNA site where they want to convert an A into an A. G – the kind of change that can make a world of difference for disorders like Rett syndrome, co-founder and chairman Nessan Bermingham has previously noted.
“All the targets that we look at, we look at them from a gain-of-function perspective,” Aiyar said. “So either increasing the half-life of a protein, or up-regulating the protein, or repairing the protein that’s at a low level, is really going to be the goal. It’s a modality in which only small molecules currently really play, but they have not been able to do so successfully because they are not very specific.
Aiyar believes these unique characteristics would allow Korro to target common indications, setting them apart from peers like Shape Therapeutics, which he says focuses on permanent editing. And AATD, with some 100,000 to 150,000 patients, is just one of them.
First introduced to the wider biotech scene by Vertex, AATD is tagged with misfolded proteins that run from the liver to the lung. Vertex tried to fix it by binding to the protein in a way it said was responsible for the misfolding, but knocked out its first candidate small molecules after deciding they were unlikely to be of benefit. clinical.
“It’s a very, very differentiated program compared to small molecule correctors because they just sit in the pocket and try to prevent misfolding, as we fix the amino acid sequence on the RNA side. to ensure proper folding, ”Aiyar said.
Delivery, he believes, will be the main challenge here. But since Korro works with mechanisms like GalNAc and LNP, Aiyar notes that “we stand on the shoulders of giants” like Alnylam and Ionis.
Eventide Asset Management led Series B, with the participation of new investors Fidelity Management & Research Company, Invus, Point72, Verition Fund Management, Monashee Investment Management, Sixty Degree Capital and an additional fund specializing in health. All existing investors have joined Atlas Venture syndicate, 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 eight months, Aiyar expects the funding to fuel an ongoing hiring drive so that Korro has enough staff to build a significant pipeline. They are developing a CNS program to balance the primary liver indication, with other chronic indications in mind, before entering the clinic, ideally within the next 18 months.
“The biology here is very new,” he said. “I think it’s going to be difficult for people to try rather than, you know, make a very concerted effort in terms of clinical development, because the last thing you want to do is go to the clinic with a compound. which looks good and then fall off the cliff really fast.