Phase 1 healthy volunteer trial of mRNA therapy RCT2100 launched

ReCode is developing genetic medicine for class I mutations in CFTR gene

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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ReCode Therapeutics has launched a Phase 1 clinical trial to evaluate the safety of RCT2100, its investigational genetic medicine for  cystic fibrosis (CF), in healthy volunteers and the first group of participants has been dosed.

RCT2100 is being developed for CF patients with class I mutations in the CFTR gene, which don’t respond to CFTR modulator therapies.

The company plans to seek clearance from the U.S. Food and Drug Administration for a Phase 1 trial involving CF patients.

“The initiation of the clinical study of RCT2100 … represents an important milestone for the CF community,” David Lockhart, PhD, chief scientific officer and president of ReCode, said in a company press release. “RCT2100 is designed to target the underlying cause of CF so that more people with CF may benefit, including those with rare mutations.”

CF is caused by mutations in the CFTR gene and affects the production or function of the CFTR protein. A dysfunctional or absent CFTR protein is the cause of most CF symptoms.

In recent years, CFTR modulators have become a mainstay treatment, but they don’t alter the underlying genetic problem and work instead to increase the faulty CFTR protein’s function.

They don’t work for all types of mutations, however. Class 1 mutations result in little or no CFTR being produced, leaving no protein for CFTR modulators to work on. These mutations are present in around 10-13% of patients, according to ReCode.

“While progress has been made for many people with CF, those who do not benefit from existing modulators report feeling left behind and continue to face profound physical and emotional hardship from the disease,” Lockhart said.

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What is RCT2100 and what does it do in CF?

RCT2100 is an inhaled medicine that’s designed to target the genetic cause of CF, a potential benefit for patients who don’t respond to or can’t use CFTR modulators.

To produce a functional protein, the genetic information in DNA is transcribed into an intermediate template molecule called messenger RNA, or mRNA, that’s read by a cell’s protein-making machinery to produce a working protein.

RCT2100 delivers a healthy version of CFTR mRNA to cells, providing them with a template their machinery can use to make a functional CFTR protein. The therapy delivers mRNA using ReCode’s Selective Organ Targeting (SORT) lipid nanoparticle (LNP) platform.

Preclinical research has indicated CFTR mRNA delivery via SORT LNP restored CFTR function in patient-derived lung cells, regardless of the type of CF-causing mutation.

The Phase 1 trial (NCT06237335) being conducted in New Zealand will assess the safety and tolerability of single ascending doses of RCT2100 among 32 healthy adult volunteers, ages 18-55.

The participants will be randomly assigned to a single dose of inhaled RCT2100 or a placebo and then monitored for safety for about a month. The trial is expected to finish in August.

ReCode’s development of RCT2100 has been supported by $50 million in series B financing as well as up to $15 million from the Cystic Fibrosis Foundation. The company also plans to collaborate with Intellia Therapeutics on developing gene-editing therapies for CF.