Ciliary Motility Disorders

– Phase 1b study will evaluate the safety and tolerability of multiple ascending doses of RCT2100 in people with cystic fibrosis – MENLO PARK, CA, USA I September 26, 2024 I ReCode Therapeutics, a clinical-stage genetic medicines company using tissue-specific delivery to power the next wave of mRNA and gene correction therapeutics, today announced that the first patient has been dosed in a Phase 1b study evaluating RCT2100, an investigational inhaled mRNA therapy for people with cystic fibrosis (CF). CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, impacting approximately 130,000 people worldwide. Although recent advancements in CFTR modulator therapies have improved outcomes for many people with CF, those with certain mutations remain underserved because these mutations prevent the production of functional CFTR protein, making current treatments ineffective. “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,” said Shehnaaz Suliman, M.D., MBA, M.Phil., chief executive officer of ReCode Therapeutics. “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.” Formulated using ReCode’s proprietary Selective Organ Targeting (SORT) lipid nanoparticle (LNP) platform, RCT2100 is designed to deliver CFTR mRNA directly to target cells in the lungs, instructing them to produce a functional version of the CFTR protein that is missing in some individuals with CF. By providing this CFTR mRNA, the therapy aims to address the root cause of CF, potentially restoring CFTR protein function in the lungs rather than just managing the symptoms. ReCode recently received global regulatory authorization to proceed with the RCT2100 Phase 1b study in the United States (U.S.), United Kingdom (UK), and Europe. The study is currently enrolling at sites in the Netherlands, with future expansion planned for France, the U.S. and the UK. For more information, please visit CF-Clinical-Studies.com . About Cystic Fibrosis Cystic fibrosis (CF) is a progressive genetic disease that causes persistent lung infections and respiratory failure. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. An estimated 105,000 people have been diagnosed with CF across 94 countries, according to the Cystic Fibrosis Foundation. The absence or dysfunction of the CFTR protein results in a defect in airway hydration, which leads to excessive mucus buildup in the lungs. It also creates a mucociliary clearance defect, recurrent infections, inflammation, respiratory failure, and other complications. Despite advancements in CFTR modulator treatments, approximately 10% of the CF community have genetic mutations that do not benefit from these life-changing therapeutics. About ReCode Therapeutics ReCode Therapeutics is a clinical-stage genetic medicines company using precision delivery to power the next wave of mRNA and gene correction therapeutics. ReCode’s proprietary Selective Organ Targeting (SORT) lipid nanoparticle (LNP) platform enables highly precise and targeted delivery of genetic medicines directly to the organs, tissues, and cells implicated in disease, enabling improved efficacy and potency. ReCode’s lead programs include RCT2100 for the treatment of the 10% of cystic fibrosis patients who have genetic mutations in the CFTR gene that do not respond to currently approved CFTR modulators and RCT1100 for the treatment of primary ciliary dyskinesia caused by pathogenic mutations in the DNAI1 gene. RCT1100 and RCT2100 are inhaled disease-modifying mRNA-based therapies formulated using the SORT LNP delivery platform. ReCode is expanding its pipeline to develop potential therapies for other rare and common genetic diseases, including musculoskeletal, central nervous system, liver, and infectious disease indications. ReCode has been recognized by the San Francisco Business Times and Silicon Valley Business Journal as a Best Place to Work. For more information, visit www.recodetx.com and follow us on LinkedIn and Instagram . SOURCE: ReCode Therapeutics

MENLO PARK, Calif.--( BUSINESS WIRE )--ReCode Therapeutics, a clinical-stage genetic medicines company using tissue-specific delivery to power the next wave of mRNA and gene correction therapeutics, today presented preclinical data from its mRNA-based cystic fibrosis (CF) program at the North American Cystic Fibrosis Conference (NACFC), taking place September 26-28, 2024, in Boston, Massachusetts. These preclinical data demonstrate that RCT2100 significantly restored CFTR function in human bronchial epithelial (HBE) cells derived from people with CF, achieving up to 135% of the efficacy seen with an elexacaftor/tezacaftor/ivacaftor equivalent in cells with an F508del mutation on one allele and a minimal function mutation on the other allele. Additionally, in vivo studies using a G551D CF ferret model revealed notable improvement in mucociliary clearance (MCC) post-treatment, highlighting RCT2100's potential to address the medical needs of approximately 10% of people with CF not eligible for current CFTR modulator therapy. "These preclinical data underscore the potential of RCT2100 as a novel therapeutic approach for people with cystic fibrosis who do not respond to existing CFTR modulators,” said Shehnaaz Suliman, M.D., MBA, M.Phil., chief executive officer of ReCode Therapeutics. “In the studies, RCT2100, an inhaled mRNA-based therapy, successfully restored CFTR function in patient-derived cells in vitro and improved mucociliary clearance, which is critical for improving patient outcomes, in a ferret model of CF lung disease. These findings support our goal of developing innovative therapies that address the needs of the entire cystic fibrosis community, especially those still awaiting effective treatment options.” “The results seen in this preclinical study are significant in that they demonstrate the ability of RCT2100 to improve CFTR function in HBE cells at a level previously only seen with triple combination CF drug modulator treatments,” said Marco Weinberg, Ph.D., Head of Research at ReCode Therapeutics. “In a separate study, the use of RCT2100 demonstrated that when used in the G551D CF ferret model, treatment resulted in a notable improvement in mucociliary clearance. This is significant in that treatment with RCT2100 resulted in an increase in MCC after two weeks, similar to that seen with existing modulator therapy after only two doses administered once per week. Combined, these data highlight the potential of RCT2100 as a treatment option for a group of CF patients that do not respond to current therapy.” ReCode is pleased to welcome NACFC participants to booth #816 in the Exhibit Hall. About Cystic Fibrosis Cystic fibrosis (CF) is a progressive genetic disease that causes persistent lung infections and respiratory failure. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. An estimated 105,000 people have been diagnosed with CF across 94 countries, according to the Cystic Fibrosis Foundation. The absence or dysfunction of the CFTR protein results in a defect in airway hydration, which leads to excessive mucus buildup in the lungs. It also creates a mucociliary clearance defect, recurrent infections, inflammation, respiratory failure, and other complications. Despite advancements in CFTR modulator treatments, approximately 10% of the CF community have genetic mutations that do not benefit from these life-changing therapeutics. About ReCode Therapeutics ReCode Therapeutics is a clinical-stage genetic medicines company using precision delivery to power the next wave of mRNA and gene correction therapeutics. ReCode’s proprietary Selective Organ Targeting (SORT) lipid nanoparticle (LNP) platform enables highly precise and targeted delivery of genetic medicines directly to the organs, tissues, and cells implicated in disease, enabling improved efficacy and potency. ReCode’s lead programs include RCT1100 for the treatment of primary ciliary dyskinesia caused by pathogenic mutations in the DNAI1 gene, and RCT2100 for the treatment of the 10% of people with cystic fibrosis who have genetic mutations in the CFTR gene that do not respond to currently approved CFTR modulators. RCT1100 and RCT2100 are inhaled disease-modifying mRNA-based therapies formulated using the SORT LNP delivery platform. ReCode is expanding its pipeline to develop potential therapies for other rare and common genetic diseases, including musculoskeletal, central nervous system, liver, and infectious disease indications. ReCode has been recognized by the San Francisco Business Times and Silicon Valley Business Journal as a Best Place to Work. For more information, visit www.recodetx.com and follow us on LinkedIn and Instagram .

Ethris' drug, ETH47, is administered through the nose and works by increasing the amount of IFNλ in the respiratory tract. Ethris’ mRNA-based treatment to prevent viral infections in people with uncontrolled asthma so far appears to be safe and increases expression of its target protein, early data suggest.  The German biotech announced June 25 interim phase 1 data on its lead candidate, ETH47, which indicate it successfully encodes the protein interferon lambda (IFNλ) in healthy people. A full readout is expected in the third quarter of 2024.  “Given the strong association between viral infections, [particularly] with rhinovirus, and asthma exacerbations, Ethris’ mRNA product candidate … has the potential to fill a significant gap in the asthma treatment paradigm,” Eric Bateman, M.D., a board member of the Global Initiative for Asthma, commented in Ethris’ press release.   People with uncontrolled asthma are more susceptible to severe respiratory viral infections than those without the condition on account of a unique inflammatory response in the lungs that dysregulates the production of interferons, including IFNλ. Viruses also make asthma worse—in fact, they’re the most common cause of asthma exacerbation.  ETH47 is administered through the nose and works by increasing the amount of IFNλ in the respiratory tract. It’s ability to circumvent the challenge of getting mRNA to the lungs is owed to the company’s lipidoid nanoparticle delivery system, SNaP LNP. Lipidoids are similar to lipid particles, like the ones used in the COVID-19 vaccines, but with some differences that make them useful for delivering mRNA both via inhalation and through injection into the muscle. Regarding side effects, Ethris said in its press release about the data that there were no clinically relevant severe or drug-related adverse events across any of the tested doses. Besides providing evidence that ETH47’s mechanism of action is safe and works as intended, the results are the first signs of clinical life for the company’s platform, stabilized non-immunogenic mRNA, or SNIM RNA. The platform is the basis for Ethris’ primary ciliary dyskinesia program, too, for which the company has three drugs in development.  As of mid-June, Ethris’ work on ETH47 is being funded in part by the Gates Foundation, which donated $5 million to get the drug ready for phase 2 trials and build out manufacturing capabilities. That financing will include an equity component that will close at the company’s next funding round. Ethris’ last round was a $26.3 million series B that closed in February 2022. Ethris previously signed a 25 million euro ($29 million) deal with AstraZeneca back in 2017 to develop therapies for respiratory diseases based on its SNIM RNA technology. The five-year agreement would have expired in 2022; it’s unclear whether the companies are still working together. FBR has reached out for comment.