ReCode Therapeutics nets $80M to push RNA treatment for cystic fibrosis

Over the years, more and more patients with cystic fibrosis have benefited from new drugs such as Vertex’s Trikafta. But there is still a subset of patients with certain mutations for whom those drugs don’t work.

Enter ReCode Therapeutics, which raised $80 million to advance a treatment for cystic fibrosis driven by what’re called nonsense mutations, as well as a treatment for another lung disease, primary ciliary dyskinesia (PCD). PCD is similar to cystic fibrosis: A group of genetic mutations causes patients to lack the protein that make up cilia—the fingerlike projections in the airways—or to make defective versions of it. Because the cilia don’t work properly, the patients can’t clear mucus normally and so suffer respiratory infections and, eventually, lose lung function, ReCode CEO David Lockhart, Ph.D., told FierceBiotech.

The funding, which comes from the likes of OrbiMed, Colt Ventures, MPM Capital and Vida Ventures, will push ReCode’s two programs through preclinical work. The company aims to move both treatments into the clinic in late 2021.

They’re both RNA treatments, but they work slightly differently. The PCD treatment delivers a messenger RNA (mRNA) with instructions for the protein that patients with PCD are missing.

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“There is an internal molecular machine in the cilia that makes them move and PCD patients are born with a defective part,” Lockhart said. “We deliver the mRNA that encodes the part that they need to get the machinery working again.”

The cystic fibrosis treatment uses transfer RNA (tRNA), which plays a role in translating mRNA instructions into a protein. It’s designed to remedy nonsense mutations, which stop DNA synthesis in its tracks, resulting in an incomplete protein that doesn’t work. The treatment, called a NanoCorrector, is engineered to recognize those “stops” and insert an amino acid in their place so that the full, functional protein is made, remedying the deficiency behind cystic fibrosis.

ReCode is zeroing in on one particular mutation each for PCD and cystic fibrosis but could follow up with more treatments for other mutations.

“Our first two lead programs on their own are very important and could be the basis of a successful company, but both of them also lead quite naturally to pipelines of their own,” Lockhart said.

The company’s next efforts in PCD and cystic fibrosis will use different active ingredients to target different mutations. But those ingredients would be formulated, delivered in a similar way to the same target cells and tested in clinical trials with the same design, he said.

“Once we are able to do this once, we should be able to do this multiple times,” Lockhart said.

Finally, the new financing will support the development of ReCode’s nonviral lipid nanoparticle delivery platform. Licensed from UT Southwestern Medical Center, it’s been shown to deliver multiple kinds of RNA in preclinical models and could be used to deliver CRISPR components like Cas9.

“It’s versatile in terms of payloads that can be used and it’s also tunable to a certain extent, so it has different biodistribution properties. The sky’s the limit on that,” Lockhart said. “Different payloads, different types of mutations, different types of RNA and gene editing. All of that will be within our purview.”

Of course, as a small company, ReCode has picked a narrow area of focus. But as it grows, it will be able to do more, and it will enlist partners if and when it moves into rare and genetic diseases beyond the lungs, Lockhart said.