First US patient dosed in Phase 1b trial testing inhaled CF therapy
RCT2100 for those not responding to, ineligible for CFTR modulator therapy
A Phase 1b trial assessing the safety of RCT2100, Recode Therapeutics’ inhaled therapy candidate for people with cystic fibrosis (CF), has now dosed its first patient in the U.S. The trial already was underway in Europe.
RCT2100 is being developed for patients who do not respond to or are not eligible for CFTR modulator therapies — individuals who, according to the company, account for about 10% of the CF community. CFTR modulator treatments are commonly used to treat people with CF caused by specific mutations.
The first U.S. patient enrolled in the Phase 1b trial (NCT06237335) was dosed at New York Medical College (NYMC).
“This milestone represents a pivotal moment for the cystic fibrosis community and reflects our ongoing commitment to advancing care for patients with CF,” Allen J. Dozor, MD, a professor at NYMC and president at Boston Children’s Health Physicians, said in an NYMC press release.
“We are proud to play a leading role in this important study and are hopeful that RCT2100 will provide a meaningful new option for those living with this challenging disease,” addded Dozor, who personally administered the dose.
The trial is still recruiting patients, ages 18 to 65, who are not eligible for or cannot tolerate CFTR modulators, at multiple sites in the U.S., France, the Netherlands, and the U.K.
Phase 1b trial of RCT2100 now ongoing in the US and Europe
A genetic disease, cystic fibrosis is caused by mutations in the CFTR gene. These mutations affect the production or function of the CFTR protein, which normally regulates the movement of salt molecules and water in and out of cells. Without this protein, thick and sticky mucus accumulates in certain organs, particularly the lungs and gastrointestinal tract.
CFTR modulators are a class of medications that work to increase the protein’s function, helping to ease CF symptoms and slow disease progression. However, they do not work for all mutation types, and some patients can’t tolerate them or don’t respond to them.
With its novel design, RCT2100 is expected to provide lung cells with a healthy version of CFTR messenger RNA (mRNA), an intermediary template molecule of the DNA-encoded information that’s needed for protein production. This allows cells to produce a functional version of CFTR, regardless of the disease-causing mutation.
“RCT2100 aims to address the underlying cause of CF, potentially improving CFTR protein function in the lungs rather than just managing symptoms,” the company states on its website.
The mRNA is delivered via inhalation — using ReCode’s Selective Organ Targeting lipid nanoparticle platform — directly to lung cells.
In preclinical studies, this technology was found to restore CFTR function in lung cells derived from CF patients.
The clinical trial is assessing RCT2100 in two parts. The first enrolled 32 healthy volunteers, randomly assigned to receive RCT2100 or a placebo, and monitored for about one month.
Now, the second part — being conducted at a total of 24 sites — is assessing the treatment’s safety and tolerability, given in multiple ascending doses, to people with CF over four weeks. The participants then are followed up for 24 weeks, or about six months.
Living with cystic fibrosis has been a long and interesting journey. … I am grateful for my medical team in getting me the proper care and providing me with the opportunity to take part in trial medications like RCT-2100.
Regarding the recently dosed patient, a man treated at NYMC in Westchester County, favorable tolerability seen with the second dose will mean that he will receive repeated doses every two to three days.
“Living with cystic fibrosis has been a long and interesting journey,” the patient said. “I am grateful for my medical team in getting me the proper care and providing me with the opportunity to take part in trial medications like RCT-2100.”
The man added: “My body took time to adjust over the holidays, but I am hopeful that 2025 will bring success in advancements in gene therapy for cystic fibrosis. I can’t wait.”
Recode is also working with Intellia Therapeutics to develop a new gene-editing treatment strategy that could alter the genetic code in patients’ cells to create a healthy version of the CFTR gene. That project will receive funding of as much as $15 million from the Cystic Fibrosis Foundation.
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