ReCode plans to use its SORT LNP genetic medicines delivery technology to treat CF and PCD patients who don’t respond to current treatments.
Pictured: David Lockhart, president and CSO, and Daniel Siegwart, co-founder of ReCode Therapeutics
Messenger RNA (mRNA)-based therapeutics have seen a boom in popularity in recent years, a space that has become increasingly competitive as pharma giants entered to produce COVID-19 vaccines and therapies that target a wider range of diseases.
Capitalizing on the progress with mRNA, CRISPR technology has quickly advanced the genetic medicine field, though one major issue that has yet to be solved is how to get these medicines to the right organs and cells in the body. LNPs have been studied as a potential solution; however, conventional LNPs are primarily taken up by the liver, limiting their ability to reach a broader range of targets.
Enter ReCode Therapeutics’ selective organ targeting (SORT) lipid nanoparticle (LNP) delivery platform.
David Lockhart, president and CSO of ReCode, told BioSpace the SORT LNP platform is the first of its kind, engineered with a biochemically distinct fifth lipid to help the body “sort” and direct the LNPs to targeted organs and cells - with the ability to bypass the liver, if desired. While initially developed for intravenous delivery, ReCode has nebulized its mRNA therapeutic so it can be inhaled.
ReCode’s lead programs are in cystic fibrosis (CF) and primary ciliary dyskinesia (PCD), a rare disease similar to CF for which currently no approved treatments exist.
“Nobody has done this successfully–created an mRNA therapy wrapped up in an LNP that is delivered into the airway and capable of directly reaching the cells involved in disease,” Lockhart said. “It’s new territory.”
Targeting the 10%
In January, the company announced it had received an investment of up to $15 million from the Cystic Fibrosis Foundation to help advance its CF treatments.
Vertex Pharmaceuticals is often regarded as the leader in the CF space. Its lead treatment, Trikafta, is the most widely used of its four available CF treatments.
When the FDA approved Trikafta in October 2019, Jeffrey Leiden, CEO of Vertex, called the approval a “milestone for CF patients and their families.”
Lockhart said ReCode is not directly trying to compete with Vertex’s approved treatments. Instead, his team wants to target the patients for whom Vertex’s treatments do not work– the 10% of CF patients who do not respond to CFTR modulators.
Vertex is also trying to target this population of patients and has partnered with Arbor Biotechnologies, CRISPR Therapeutics and Moderna to develop a treatment to do so. Like ReCode, its website states it also plans to use mRNA and gene editing-based approaches, but no other company has yet been able to replicate ReCode’s technology.
An Unmet Need
In March, ReCode announced it had initiated a Phase I trial studying its PCD treatment, RCT1100, in healthy participants.
Lockhart said, “In some ways, children with PCD seem very similar to children with CF, as they are both genetic diseases and patients undergo similar care methods. The significant difference lies in the underlying cause of disease.
PCD occurs when the cilia, which look like tiny fingers in the airway, don’t work as they should and cannot clear mucus from the respiratory tract. CF patients cannot transport water and salt across cell membranes, so mucus builds up in the lungs, digestive tract and other areas.”
Despite this crucial difference, Lockhart said due to the similarities between the two diseases, the path through the clinic will likely be similar. Because PCD is much less common than CF, fewer companies are working to develop a treatment.
He said that because the first dosing of healthy patients with ReCode’s PCD treatment was successful, he expects the pathway for its CF treatment to be just as smooth.
“[Entering the clinic] is exciting because it shows that it’s completely doable, and now, we’re doing the same thing in cystic fibrosis,” Lockhart said. “This program is following a very similar trajectory as our PCD treatment.”
He said ReCode expects to submit regulatory filings to begin clinical trials for its inhaled CF mRNA candidate this year and hopes to enter the clinic in early 2024.
As for the company’s long-term goals, Lockhart said that besides advancing its two lead programs, he wants it to move beyond respiratory diseases. ReCode plans to use the SORT LNP technology to deliver gene editing and correction machinery to correct disease-causing mutations. If the technology is delivered in the right way, he said, it could be curative.
“It’s not easy . . . but it’s a very important goal, and now, it feels like one that’s actually doable, whereas before, it seemed more like a dream,” he said.
