Boehringer Ingelheim and partners start clinical development of a first-in-class, inhaled gene therapy for people with cystic fibrosis

Ingelheim, Germany, 20 February 2025 – Boehringer Ingelheim, IP Group, the UK Respiratory Gene Therapy Consortium (GTC)¹ and OXB,¹ today announce the start of LENTICLAIR^TM 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 LENTICLAIR^TM 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 LENTICLAIR^TM 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 LENTICLAIR^TM-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.

About Boehringer Ingelheim

Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at https://www.boehringer-ingelheim.com or for UK at www.boehringer-ingelheim.com/uk .

About OXB
OXB (LSE: OXB) is a quality and innovation-led contract development and manufacturing organisation (CDMO) in cell and gene therapy with a mission to enable its clients to deliver life changing therapies to patients around the world.
One of the original pioneers in cell and gene therapy, OXB has more than 25 years of experience in viral vectors; the driving force behind the majority of cell and gene therapies. OXB collaborates with some of the world’s most innovative pharmaceutical and biotechnology companies, providing viral vector development and manufacturing expertise in lentivirus, adeno-associated virus (AAV), adenovirus, and other viral vector types. OXB’s world-class capabilities span from early-stage development to commercialisation. These capabilities are supported by robust quality-assurance systems, analytical methods and depth of regulatory expertise.
OXB offers a vast number of unique technologies for viral vector manufacturing, including a 4th generation lentiviral vector system (the Tetravecta™ system), dual plasmid system for AAV production, suspension and perfusion process using process enhancers and stable producer and packaging cell lines.
OXB, a FTSE4Good constituent, is headquartered in Oxford, UK. It has bioprocessing and manufacturing facilities across Oxfordshire, UK, Lyon and Strasbourg, France, and near Boston, MA, US. Learn more at www.oxb.com.

About the UK Respiratory Gene Therapy Consortium
The UK Cystic Fibrosis Gene Therapy Consortium (GTC) comprises researchers from Imperial College London and the Universities of Oxford and Edinburgh. In 2001, the groups joined together as one organisation to share expertise and funding with a single common goal of making gene therapy for CF patients a clinical reality. The GTC has undertaken six non-viral Phase 1/2a proof-of-concept studies and the first Phase 2b gene therapy trial for CF, which met its primary endpoint. In parallel, it has developed the novel lentiviral vector which will be used in this first-in-human trial. Further details and commentary can be found at www.respiratorygenetherapy.org.uk

*UK Respiratory Gene Therapy Consortium Funders have included:
About the Cystic Fibrosis Trust
Cystic Fibrosis Trust is the only UK-wide charity dedicated to uniting for a life unlimited for everyone affected by cystic fibrosis.  
The Trust funds cutting edge research, and provides confidential advice, support, and information on any aspect of cystic fibrosis, including help with financial support. 
To contact the Cystic Fibrosis Trust Helpline call (+44) 0300 373 1000 or (+44) 020 3795 2184. 
The work the Trust does is only made possible by generous donations from supporters. Visit www.cysticfibrosis.org.uk to find out more about cystic fibrosis, the work of the Trust and how you can help. 

About the Health Innovation Challenge Fund
The Health Innovation Challenge Fund was a parallel funding partnership between Wellcome and the Department of Health and Social Care.  The main goal of the partnership was to stimulate the creation of innovative healthcare products, technologies and interventions and to facilitate their development for the benefit of patients in the NHS and beyond.

About Wellcome
Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health.

The National Institutes of Health and Care Research through the Imperial Biomedical
Research Centre, the Royal Brompton Clinical Research Facility, and Senior Investigator Awards to Professors Jane Davies and Eric Alton.

Media Contacts:

Boehringer Ingelheim
Reinhard Malin                 
+49 (6132) 77-90815                                 
reinhard.malin@boehringer-ingelheim.com

Linda Ruckel
203-791-6672
linda.ruckel@boehringer-ingelheim.com

References

¹ The GTC consists of researchers from Imperial College London and the Universities of Oxford and Edinburgh.
¹ Oxford Biomedica rebranded as OXB in September 2024.

¹ CinicalTrials.gov. A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1). Available at: https://clinicaltrials.gov/study/NCT06515002. Accessed: December 2024.
² Guo, J., Garratt, A. & Hill, A. Worldwide rates of diagnosis and effective treatment for cystic fibrosis. J. Cyst. Fibros. 21(3), 456–462. https://doi.org/10.1016/j.jcf.2022.01.009 (2022)
³ Bareil C, Bergougnoux A. CFTR gene variants, epidemiology and molecular pathology. Archives de Pédiatrie 27 (2020) eS8–eS12.
⁴ Allen L et al. Future therapies for cystic fibrosis. Nat Commun. 2023 Feb 8;14:693. doi: 10.1038/s41467-023-36244-2