First CF patient dosed in early trial testing inhaled gene therapy
RCT2100 is designed to provide cells with healthy CFTR protein using mRNA
A Phase 1b study that’s evaluating the safety of RCT2100, ReCode Therapeutics‘ investigational genetic medicine for people with cystic fibrosis (CF), has dosed its first patient. The inhalation therapy is being developed for CF patients who don’t respond to CFTR modulator therapies.
“The initiation of our Phase 1b study of RCT2100 in cystic fibrosis marks a significant milestone for us and is a step closer to offering new hope to those who cannot benefit from existing CF therapies,” Shehnaaz Suliman, MD, ReCode’s CEO, said in a company press release.
In CF, mutations in the CFTR gene affect the production or function of the CFTR protein. Without it, thick and sticky mucus builds up in various organs, including the lungs, liver, pancreas, and intestines.
CFTR modulators are a class of medicines that increase the faulty CFTR protein’s function. They don’t work for all mutation types, including Class 1, in which little or no CFTR is produced, however. About 10% to 13% of CF patients carry mutations that don’t benefit from these therapeutics, according to ReCode.
Delivered via inhalation using ReCode’s Selective Organ Targeting (SORT) lipid nanoparticle (LNP) platform, RCT2100 is designed to provide cells with a healthy version of CFTR using messenger RNA, or mRNA. To make a protein, the genetic information encoded in DNA is transcribed into mRNA, an intermediate template molecule. This lets the cell’s protein-making machinery produce a working CFTR protein regardless of the type of CF-causing mutation.
Testing inhaled RCT2100 in CF
The gene therapy seeks to address the underlying cause of CF, potentially restoring CFTR’s function in the lungs.
In preclinical studies, CFTR mRNA delivered by SORT LNP restored CFTR function in lung cells derived from CF patients. The first-in-human Phase 1 study (NCT06237335)Â opened in New Zealand and is assessing RCT2100 in two parts.
Dosing began in the study’s first part involving 32 healthy adult volunteers, ages 18-55, to assess the safety and tolerability of single ascending doses of RCT2100. Participants will be randomly assigned to inhaled RCT2100 or a placebo and monitored for about a month.
The second part, or Phase 1b, is testing the safety and tolerability of multiple ascending doses of RCT2100 in people with CF. Here, participants will be followed for 24 weeks, or about six months.
The company recently received global regulatory authorization to proceed with the Phase 1b part in the U.S., U.K. and Europe, where a site in the Netherlands is now enrolling patients. Expansion is planned for France, the U.K., and across the U.S.
“We are immensely grateful for the ongoing support and partnership of the CF patient community and are focused on accelerating enrollment to bring this potential new treatment to those in need as quickly as possible,” Suliman said.
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