Korro Bio is moving back to square one as a preclinical biotech after the failure of KRRO-110 in alpha-1 antitrypsin deficiency. The company’s stock is down 80% on all the news.
Korro Bio is experiencing a comedy of failures from the clinic to the boardroom. The RNA editing biotech’s only clinical candidate is being abandoned after failing a Phase I/IIa trial. A third of staff are being laid off. The chief medical officer has resigned. And Novo Nordisk has placed a year-long partnership on hold.
With so much bad news packed into its third quarter earnings release issued Wednesday afternoon, Korro’s shares slid by just under 80% to $6.56 on Thursday morning.
Starting with the clinical flop that triggered it all, KRRO-110 failed to produce adequate levels of a key protein associated with a genetic lung and liver disease. The REWRITE trial was testing the candidate, an RNA editing oligonucleotide delivered via a lipid nanoparticle (LNP) delivery system, in healthy volunteers and clinically stable patients with alpha-1 antitrypsin deficiency (AATD), a genetic disease where patients lack the alpha-1 antitrypsin (AAT) protein. The condition can lead to damage in the lungs and liver, including advancement to chronic obstructive pulmonary disease or cirrhosis of the liver.
While Korro noted an increase in the functional M-AAT protein, the results were not high enough to meet the bar for statistical significance after a single administration that the biotech had set based on preclinical evidence.
William Blair analysts in a note to clients Thursday morning called the data disappointing.
“On the one hand, the presence of M-AAT in AATD patients is yet another validation of viable ADAR-mediated editing in humans; on the other hand, the KRRO-110 clinical profile looks non-competitive at the moment,” the analysts wrote.
The results of the REWRITE trial did not beat what peers Wave Life Sciences and Beam Therapeutics have achieved with their candidates, William Blair said.
Against Its Thesis
Korro will now move on to Plan B. The company intends to name a new development AATD candidate using the GalNAc mechanism in the first half of 2026, CEO Ram Aiyar said in a statement accompanying the earnings release.
William Blair worries that Korro is heading into crowded territory with the GalNAc conjugation, as Wave and AiRNA are already well ahead in the clinic.
“This switch also goes against the company’s own thesis that LNPs may be the most efficient delivery mechanism for SERPINA1-correcting oligos, but management made the decision to transition to GalNAc based on capital constraints rather than switching to a new LNP or conducting further work to understand the AATD patient-specific pharmacokinetic shortcomings of KRRO-110,” William Blair wrote.
In addition to moving on from KRRO-110, Korro is undergoing a strategic restructuring, which will claim about a third of staff and extend the biotech’s cash runway into the first half of 2027. The layoffs will cost about $2.4 million in one-time severance and other termination costs. Chief Medical Officer Kemi Olugemo has also resigned, effective Wednesday.
Meanwhile, Novo is placing a 12-month pause on a partnership with Korro that began in September 2024 to “reassess the rationale for the current target under the first research program.” The update is a change from second-quarter earnings, where Korro said it was advancing the central nervous system programs with Novo, with up to two programs expected to head into preclinical development.
Novo offered up to $530 million in upfront, development and commercial milestones to work with Korro on RNA editing candidates, with an initial focus on cardiometabolic diseases.
In signs that Korro will keep moving forward despite all the setbakcs, the company nominated a GalNAc conjugation candidate called KRRO-121 to be developed for hyperammonemia, including urea cycle disorders and hepatic encephalopathy.
The biotech had $102.5 million in cash on hand as of September 30.
