Boehringer Ingelheim and partners start clinical development of a first-in-class, inhaled gene therapy for people with cystic fibrosis
February 24, 2025 – Biotechnology – cystic fibrosis, first-in-class, gene therapy
Ingelheim, Germany – Boehringer Ingelheim, IP Group, the UK Respiratory Gene Therapy Consortium (GTC)1 and OXB,1 today announce the start of LENTICLAIRTM 1, a Phase I/II trial of BI 3720931, a novel, first-in-class, gene therapy aiming to improve disease outcomes in people with cystic fibrosis (CF), regardless of gene mutations that are causing the disease. The trial specifically focuses on adults with CF who genetically cannot benefit from cystic fibrosis transmembrane conductance regulator (CFTR) modulators.1
CF is a hereditary, lifelong disease that progresses in severity over time, and affects more than 100,000 people worldwide.2 CF is caused by mutations in the CFTR gene. These mutations cause the CFTR protein to become dysfunctional, which leads to the development of sticky, thick mucus clogging the airways, which causes long-lasting lung infections that increasingly limit the person’s ability to breathe. More than 2,000 known mutations of this gene lead to different levels of severity of the disease, depending on the specific mutations that have occurred.3 Treatment with CFTR modulators, which target the underlying defects in the CFTR protein, has brought progress for people with specific mutations. Unfortunately, these treatments are not suitable for 10-15% of people with CF, either because of their mutation type or due to intolerance of modulators.4
BI 3720931 is a first-in-class, inhaled lentiviral vector-based gene therapy that could potentially address unmet needs by inserting a functional copy of the CFTR gene in the DNA of airway epithelial cells. The aim is to improve lung function and reduce exacerbations for people with CF irrespective of their mutations, including those who genetically cannot benefit from CFTR modulators.
“We are very excited about the start of the LENTICLAIRTM 1 First-In-Human trial and how BI 3720931 could potentially improve the lives of people living with CF, and who are unable to benefit from current CFTR modulators”, said Dr. Paola Casarosa, Member of the Board of Managing Directors at Boehringer Ingelheim with responsibility for the Innovation Unit. “This is a crucial moment in the development of BI 3720931, which we have progressed together with our partners since 2018. The partnership with the GTC and OXB provides an excellent example of the progress that can be made when diverse organizations and people come together with a long-term, shared goal to create a new paradigm of care.”
Professor Eric Alton of Imperial College London’s National Heart and Lung Institute, who coordinates the GTC, added, “The GTC is very excited to have reached this milestone after 24 years of focused effort and in close collaboration with our partners and people with CF. While the immediate target are those adult patients who are not eligible for CFTR modulators, this novel therapy has the potential to achieve long-lasting CFTR function improvement and disease modification for people with CF irrespective of mutation type and has the potential for re-dosing if needed. We are very grateful to our wonderful team, our partners and funders* and those with CF who have and continue to support us in many ways, including taking part in the multiple trials.”
Dr. Frank Mathias, Chief Executive Officer of OXB, said, “We are delighted that Boehringer Ingelheim is using OXB’s proprietary lentiviral vector manufacturing technology, to produce lentiviral vector for their highly innovative, inhaled cystic fibrosis gene therapy as they progress BI 3720931 through the clinic.”
The LENTICLAIRTM 1, Phase I/II First-In-Human trial will evaluate safety, tolerability, and efficacy of BI 3720931 in adults with cystic fibrosis, who are not eligible for CFTR modulator therapy. The trial has two parts. In the Phase I-part, different doses of the treatment will be given to evaluate safety, tolerability and select doses for Phase II. In the Phase II-part, two selected doses or placebo will be given in a randomized, double-blind placebo-controlled trial to assess clinical efficacy and safety.1 After completion of the 24-week trial period, trial participants will take part in a long-term follow-up trial LENTICLAIRTM-ON.
The trial is expected to be completed in early 2027. Additional information about the Phase I/II trial is available via ClinicalTrials.gov (NCT06515002).1 BI 3720931 is an investigational therapy that has not been approved for use in any country. The efficacy and safety of BI 3720931 has not yet been established.
