Korro Bio Raises $116 Million for RNA Editing Program

Korro Bio, a Massachusetts-based biotech, has landed $116 million in a Series B financing round to fund its RNA editing program, which will first target alpha-1 antitrypsin deficiency (AATD), an inherited disorder that affects the lungs and liver. 

Eventide Asset Management led the Series B round, which saw participation from new investors Fidelity Management & Research Company LLC, Invus, Point72, Verition Fund Management, Monashee Investment Management, Sixty Degree Capital and an additional healthcare specialist fund. All existing investors took part, including 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.

Founded by Atlas Venture in 2019, Korro’s second funding round surpassed the $91.5 million it raised in Series A in Sep 2020. 

Related article: An Interview with the Co-founder of Korro Bio

RNA Editing to Treat AATD

Alpha-1 trypsin is a protein that protects the lungs from the body’s own enzymes. AATD happens when a person inherits a faulty version of the gene which regulates alpha-1 trypsin (AAT) production from one or both of their parents. A faulty copy of the gene produces a misfolded AAT protein, which sticks together and stops the protein from leaving the liver where it is produced. AAT accumulates in the liver instead, and causes toxicity.  The imbalance in AAT levels ultimately lead to damage of the lungs and scarring of the liver.

Korro Bio is taking the RNA editing route to treat AATD. Its RNA editing platform OPERA uses the base editing system found in the body to repair mutations at the RNA. OPERA specifically uses oligonucleotide guides to recruit  adenosine deaminase acting on RNA (ADAR) to edit a single RNA base – from adenosine (A) to guanosine (G).

A Tricky Target

However, AATD is a tricky target to treat. No cure currently exists, and the condition is mainly managed by addressing symptoms of lung or liver disease, such as using bronchodilators or antibiotics for infections. AAT augmentation, or AAT replacement therapy, is also used, where functional AAT from healthy donors is infused into the patient. 

Vertex had banked on its small molecule drug VX-864 to correct the misfolding of AAT and bring up functional AAT levels in the body. While its Phase 2 study showed that the drug did work, Vertex concluded that the magnitude of its effects did not translate into meaningful clinical benefit, and shelved its candidate to pursue others. 

Meanwhile, Arrowhead Pharmaceuticals has shot ahead of the competition by using RNA interference to treat liver disease associated with AATD. The California-based pharma’s lead asset, ARO-AAT has shown promise in Phase 2 trials. ARO-AAT also caught the attention of Takeda, which struck a deal worth over $1 billion to co-develop the drug. 

Dicerna has further confirmed the RNAi approach with positive results from Phase 1 trials of Belcesiran, its candidate for AATD. The company is currently recruiting for its Phase 2 study. 

And playing from left field is Intellia, which is pursuing a gene therapy for AATD. The company is using CRISPR/Cas9 to knock out the abnormal gene and insert a healthy gene that promotes the production of functional AAT. Last October, the company revealed preclinical findings showing the potential of gene therapy in the disease on non-human primates.

Author

Joy Lin

Without knowledge, there is no imagination. Without imagination, knowledge is meaningless