navocaftor (SION-3067) / AbbVie, Galapagos, Sionna Therap - LARVOL DELTA

Rescue of Mutant CFTR Channel Activity by Investigational Co-Potentiator Therapy. (PubMed, Biomedicines) - "Objective/ We synthesized a new set of LSO-24 structure-based compounds, screened their effects on p.Arg334Trp-CFTR activity, and assessed the additivity of hit compounds to VX-770, ABBV-974, ABBV-3067, and apigenin. Our data suggest that these new potentiators might share a common mechanism with apigenin, which is conceivably distinct from that of VX-770 and ABBV-3067. The additive rescue of p.Arg334Trp-, p.Ser549Arg-, p.Gly551Asp-, and p.Ser945Leu-CFTR also indicates that these variants could benefit from the development of a co-potentiator therapy."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Sionna Therapeutics Expands Pipeline with Multiple Clinical Stage Cystic Fibrosis Compounds Through a License Agreement with AbbVie (PRNewswire) - "Sionna Therapeutics...announced that it has obtained exclusive worldwide rights to develop and commercialize multiple clinical-stage compounds through a license agreement with AbbVie. Under the terms of the agreement, Sionna will assume all development responsibilities for galicaftor (ABBV-2222), a transmembrane domain 1 (TMD1)-directed cystic fibrosis transmembrane conductance regulator (CFTR) corrector, and navocaftor (ABBV-3067), a CFTR potentiator, both of which have completed Phase 2 studies, and a Phase 1 TMD1-directed corrector, ABBV-2851. Sionna will prioritize advancing one of the AbbVie compounds and SION-109 as potential dual combination options with a first nucleotide binding domain (NBD1) stabilizer. AbbVie will receive an upfront payment, an equity investment in Sionna and will be eligible to receive late-stage development and commercial milestones and royalties."

Licensing / partnership • Cystic Fibrosis

Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Adult Participants With Cystic Fibrosis (clinicaltrials.gov) - P2 | N=48 | Terminated | Sponsor: AbbVie | Active, not recruiting ➔ Terminated; Strategic considerations

Adverse events • Combination therapy • Trial termination • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Adult Participants With Cystic Fibrosis (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting | N=90 ➔ 48 | Trial completion date: Nov 2023 ➔ Jun 2023 | Trial primary completion date: Oct 2023 ➔ Jun 2023

Adverse events • Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Adult Participants With Cystic Fibrosis (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: AbbVie | Active, not recruiting ➔ Recruiting

Adverse events • Combination therapy • Enrollment open • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

M23-492 FE: A Study to Assess How Food Affects the Safety and Pharmacokinetics of Galicaftor and Navocaftor (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed | Trial completion date: Mar 2023 ➔ Dec 2022 | Trial primary completion date: Mar 2023 ➔ Dec 2022

Trial completion • Trial completion date • Trial primary completion date

M23-492 FE: A Study to Assess How Food Affects the Safety and Pharmacokinetics of Galicaftor and Navocaftor (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed

Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Adult Participants With Cystic Fibrosis (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Oct 2022 ➔ Nov 2023 | Trial primary completion date: Sep 2022 ➔ Oct 2023

Adverse events • Combination therapy • Trial completion date • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

M23-492 FE: A Study to Assess How Food Affects the Safety and Pharmacokinetics of Galicaftor and Navocaftor (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open

M23-492 FE: A Study to Assess How Food Affects the Safety and Pharmacokinetics of Galicaftor and Navocaftor (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: AbbVie

New P1 trial

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2 | N=78 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed | N=189 ➔ 78

Combination therapy • Enrollment change • Trial completion • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2 | N=189 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 Combination Therapy in Adult Participants With Cystic Fibrosis (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Combination therapy • Enrollment closed • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2 | N=189 | Recruiting | Sponsor: AbbVie | Trial primary completion date: Jan 2022 ➔ Jun 2022

Combination therapy • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Study of Galicaftor/Navocaftor/ABBV-119 Combination Therapy in Subjects with Cystic Fibrosis. (clinicaltrialsregister.eu) - P2; N=90; Ongoing; Sponsor: AbbVie Deutschland GmbH & Co. KG

Clinical • Combination therapy • New P2 trial • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2; N=189; Recruiting; Sponsor: AbbVie; Trial completion date: Jan 2022 ➔ Oct 2022

Clinical • Combination therapy • Trial completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2; N=189; Recruiting; Sponsor: AbbVie; Trial primary completion date: Feb 2021 ➔ Jan 2022

Clinical • Combination therapy • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2; N=189; Recruiting; Sponsor: AbbVie; Trial completion date: Jul 2021 ➔ Jan 2022

Clinical • Combination therapy • Trial completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

ABBV-2222 + ABBV-3067: Data from P2 trial (NCT03969888) for cystic fibrosis in 2021 (AbbVie) - R & D Deep Dive

P2 data

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2; N=189; Recruiting; Sponsor: AbbVie; Not yet recruiting ➔ Recruiting; Trial completion date: Apr 2021 ➔ Aug 2021

Clinical • Combination therapy • Enrollment open • Trial completion date

A Phase 2 Study of ABBV-3067 Alone and in Combination With ABBV-2222 (clinicaltrials.gov) - P2; N=189; Not yet recruiting; Sponsor: AbbVie

Clinical • Combination therapy • New P2 trial