BI 3720931 / Oxford Biomedica, Boehringer Ingelheim - LARVOL DELTA

F/HN-pseudotyped lentiviral vector efficiently transduces non-human primate airways with no evidence of relevant toxicity. (PubMed, Mol Ther Adv) - "We have developed a third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV.F/HN) expressing functional cystic fibrosis transmembrane conductance regulator (CFTR) as a gene therapy for cystic fibrosis (BI 3720931)...Vector-specific mRNA levels were ∼45× endogenous CFTR mRNA levels in lung epithelium and ∼16× in bronchial brushings. This study extends earlier findings of rSIV.F/HN-based in vivo gene transfer in mice to NHPs, demonstrating transduction efficiency without relevant toxicity."

Journal • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CFTR

BI 3720931 Lenti-CFTR Gene Therapy Program: development of a clinical assay to monitor for reversion to replication competent lentivirus (RCL). (ASGCT 2026) - "5) United States Pharmacopeia. The Rejection of Outlying or Aberrant Observation, Design and Analysis of Biological Assays"

Clinical • Gene therapy • Cystic Fibrosis • Gene Therapies • Immunology • Inflammation • Pneumonia • Respiratory Diseases • CFTR

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Boehringer Ingelheim | Trial completion date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Oct 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Long-term Study to Monitor the Health Status of People With Cystic Fibrosis Who Took Part in a Previous Study With BI 3720931 (Lenticlair™-ON) (clinicaltrials.gov) - P1/2 | N=5 | Active, not recruiting | Sponsor: Boehringer Ingelheim

Trial initiation date • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Boehringer Ingelheim | Trial completion date: Feb 2026 ➔ Oct 2025 | Trial primary completion date: Feb 2026 ➔ Oct 2025

Trial completion date • Trial primary completion date • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Long-term Study to Monitor the Health Status of People With Cystic Fibrosis Who Took Part in a Previous Study With BI 3720931 (Lenticlair™-ON) (clinicaltrials.gov) - P1/2 | N=5 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting | N=285 ➔ 5 | Trial completion date: Nov 2048 ➔ Oct 2040 | Trial primary completion date: Nov 2048 ➔ Oct 2040

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Boehringer Ingelheim | N=36 ➔ 5 | Trial completion date: Jul 2028 ➔ Feb 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2028 ➔ Feb 2026; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Long-term Study to Monitor the Health Status of People With Cystic Fibrosis Who Took Part in a Previous Study With BI 3720931 (Lenticlair™-ON) (clinicaltrials.gov) - P1/2 | N=285 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2048 ➔ Nov 2048 | Trial primary completion date: Aug 2048 ➔ Nov 2048

Trial completion date • Trial primary completion date • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Mar 2028 ➔ Jul 2028 | Trial primary completion date: Nov 2027 ➔ Mar 2028

Trial completion date • Trial primary completion date • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Lenticlair™ 1: A Phase 1/2 trial evaluating the safety, tolerability and efficacy of an inhaled F/HN-pseudotyped lentiviral vector for CF gene therapy in people with CF ineligible for CFTR modulators (ESGCT 2024) - "The trial is planned to begin in 2024. The trial will evaluate safety and efficacy of BI 3720931 over 24 weeks in pwCF who are ineligible for CFTRmt."

Clinical • Gene therapy • P1/2 data • Viral vector • Cystic Fibrosis • Gene Therapies • Immunology • Respiratory Diseases • CFTR

Lenticlair™-ON: An extension trial examining long-term safety and efficacy outcomes associated with an inhaled F/HN-pseudotyped lentiviral vector for CF gene therapy in people with CF (ESGCT 2024) - "This extension trial will allow seamless rollover of the first participant from the FiH Lenticlair™ 1 trial. This trial will investigate long-term safety and the duration of efficacy in pwCF treated with BI 3720931."

Clinical • Gene therapy • Viral vector • Cystic Fibrosis • Gene Therapies • Immunology • Respiratory Diseases • CFTR

Administration of lentiviral vector doses achieving high transduction efficiency is well tolerated in mice (ESGCT 2024) - "These data, together with other preclinical data, support further progression of BI 3720931 towards the clinic. A first-in-human, Phase 1/2 trial (Lenticlair™ 1) to evaluate the safety and efficacy of BI 3720931 in pwCF who are genetically ineligible for CFTR modulator therapy is planned to begin in 2024."

Preclinical • Viral vector • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR • TNFA

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Suspended ➔ Active, not recruiting

Enrollment closed • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=36 | Suspended | Sponsor: Boehringer Ingelheim | Trial completion date: Apr 2027 ➔ Feb 2028 | Recruiting ➔ Suspended | Trial primary completion date: Dec 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Trial suspension • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Long-term Study to Monitor the Health Status of People With Cystic Fibrosis Who Took Part in a Previous Study With BI 3720931 (Lenticlair™-ON) (clinicaltrials.gov) - P1/2 | N=285 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Sep 2047 ➔ Jul 2048 | Trial primary completion date: Sep 2047 ➔ Jul 2048

Trial completion date • Trial primary completion date • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Long-term Study to Monitor the Health Status of People With Cystic Fibrosis Who Took Part in a Previous Study With BI 3720931 (Lenticlair™-ON) (clinicaltrials.gov) - P1/2 | N=285 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Long-term Study to Monitor the Health Status of People With Cystic Fibrosis Who Took Part in a Previous Study With BI 3720931 (Lenticlair™-ON) (clinicaltrials.gov) - P1/2 | N=285 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1/2 trial • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Boehringer Ingelheim and partners start clinical development of a first-in-class, inhaled gene therapy for people with cystic fibrosis (GlobeNewswire) - "Boehringer Ingelheim...today announce the start of LENTICLAIR 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...The trial is expected to be completed in early 2027."

Trial completion date • Trial status • Cystic Fibrosis

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Viral vector • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-In-Human Trial. (PubMed, Am J Respir Crit Care Med) - "A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV.F/HN) has been developed for the treatment of cystic fibrosis. Promising preclinical results support the progression of this vector carrying a full-length CFTR transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024."

Gene therapy • Journal • P1 data • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Comprehensive methods to assess pharmacokinetics and monitor for viral shedding, replication competence, and immunogenicity of BI 3720931 in the first-in-human Lenticlair 1 Phase I/II trial (NACFC 2024) - "Because BI 3720931 is the first-of-its-kind lentiviral gene therapy being investigated in CF, a unique and thorough strategy to monitor its safety and tolerability is required. This panel of novel assays complies with regulatory guidelines outlined for gene therapies and supports the monitoring of safety and tolerability of BI 3720931 in Lenticlair 1 and its extension trial, Lenticlair-ON, in PwCF. CRCs (mean (SD) out of 5)."

P1/2 data • PK/PD data • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Respiratory Diseases • CFTR

A Study to Test How Well BI 3720931 is Tolerated and Whether it Improves Lung Function in People With Cystic Fibrosis (Lenticlair™ 1) (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: Boehringer Ingelheim | Phase classification: P ➔ P1/2

Gene therapy • Phase classification • Trial completion date • Trial initiation date • Trial primary completion date • Viral vector • Cystic Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Lenticlair™-ON: An extension trial examining long-term safety and efficacy outcomes associated with an inhaled F/HN-pseudotyped lentiviral vector for CF gene therapy in people with CF (ECFS 2024) - "This trial will investigate long-term safety in pwCF treated with at least one BI 3720931 dose, assess efficacy duration after initial dosing and determine efficacy and safety after re-dosing, as applicable."

Clinical • Gene therapy • Viral vector • Cystic Fibrosis • Gene Therapies • Immunology • Pulmonary Disease • Respiratory Diseases

Lenticlair™ 1: A Phase 1/2 trial evaluating the safety, tolerability and efficacy of an inhaled F/HN-pseudotyped lentiviral vector for CF gene therapy in people with CF ineligible for CFTR modulators (ECFS 2024) - "This trial will evaluate the safety and efficacy of BI 3720931 over 24 weeks in pwCF who are ineligible for CFTRmt. A separate trial will monitor long-term safety for 15 years."

Clinical • Gene therapy • P1/2 data • Viral vector • Cystic Fibrosis • Gene Therapies • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

F/HN pseudotyped lentiviral vector‐mediated transduction of non‐human primates (ESGCT 2023) - "Objectives: We have developed a lentiviral vector pseudotyped with the Sendai virus F and HN envelope proteins (BI 3720931) for cystic fibrosis (CF) gene therapy... This study confirms and extends our previous findings of rSIV.F/HN-based in vivo gene transfer in mice. Using a relatively low vector dose, NHPs demonstrated transduction efficiency in the range of values likely to relate to clinical benefit, without evidence of toxicity. Transduction efficiency and toxicology in animals treated with a higher dose is currently being analysed."

Viral vector • Cystic Fibrosis • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases