cavosonstat (PBA-003) / Laurel Therap, Path BioAnalytics - LARVOL DELTA

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2 | N=395 | Completed | Sponsor: University of North Carolina, Chapel Hill | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Mar 2025

Trial completion • Trial completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Precision Medicine Trial of Cavosonstat for the Treatment of Adults with Severe and/or Exacerbation Prone Asthma (ATS 2025) - No abstract available

Clinical • Late-breaking abstract • Asthma • Immunology • Respiratory Diseases

B6 PRECISION MEDICINE IN SEVERE ASTHMA: LATE-BREAKING RESULTS FROM THE PRECISE TRIAL (ATS 2025) - "Objectives describe new thinking about how to design and interpret biomarker-stratified adaptive platform trialsdescribe new findings about the following interventions targeting new pathways in severe and exacerbation-prone asthma: medium chain triglycerides, cavosonstat, imatinib, Broncho-Vaxom®, and clazakizumablearn how established and new biomarkers can predict asthma severity and response to therapy. The learner can apply this new knowledge in clinical practice to improve the care of severe asthmatics"

Late-breaking abstract • Asthma • Immunology • Respiratory Diseases

The role of S-nitrosoglutathione reductase (GSNOR) in T cell-mediated immunopathology of experimental autoimmune encephalomyelitis (EAE). (PubMed, Neuroscience) - "Previously, we reported that both S-nitrosoglutathione (GSNO), a carrier of cellular nitric oxide, and N6022, an injectable form of GSNO reductase (GSNOR) inhibitor that increases endogenous GSNO levels, alleviate experimental autoimmune encephalomyelitis (EAE) in mice by suppressing Th1 and Th17 immune responses. This observation underscores the potential of increased GSNOR expression and activity as a risk factor exacerbating EAE immunopathology, while simultaneously highlighting its potential as a target for modifying the disease. Furthermore, the balanced immune regulation provided by orally active N91115 (IL-6/IL-17a vs. IL-10) presents a promising alternative to immunosuppressive drugs, reducing the risk of opportunistic infections."

Journal • CNS Disorders • Immunology • Infectious Disease • Multiple Sclerosis • IL10 • IL17A • IL6

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2 | N=395 | Active, not recruiting | Sponsor: University of North Carolina, Chapel Hill | Recruiting ➔ Active, not recruiting | N=600 ➔ 395

Enrollment change • Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). (PubMed, Cochrane Database Syst Rev) - "There is insufficient evidence of clinically important effects from corrector monotherapy in pwCF with F508del/F508del. Additional data in this review reduced the evidence for efficacy of dual therapy; these agents can no longer be considered as standard therapy. Their use may be appropriate in exceptional circumstances (e.g. if triple therapy is not tolerated or due to age). Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar small improvements in QoL and respiratory function with lower pulmonary exacerbation rates. While the effect sizes for QoL and FEV still favour treatment, they have reduced compared to our previous findings. Lumacaftor-ivacaftor was associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (not observed for tezacaftor-ivacaftor). Tezacaftor-ivacaftor has a better safety profile, although data are lacking in children under 12 years. In this population,..."

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

Systematic review of corrector modulator therapy for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del) (NACFC 2023) - " Thirty-four RCTs were included (4,781 participants): eight monotherapy RCTs (4PBA, CPX, lumacaftor, cavosonstat, FDL 169), 15 dual-therapy RCTs (lumacaftor-ivacaftor or tezacaftor-ivacaftor), and 11 triple-therapy RCTs (elexacaftor-tezacaftor-ivacaftor [ETI], VX-659-teza-caftor-ivacaftor, VX-440-tezacaftor-ivacaftor, VX-152-tezacaftor-ivacaftor). There is no evidence to support monotherapy and limited evidence to support dual therapy for PwCF who have a class II CFTR gene variant. Clinically relevant differences were found in key outcomes in the triple therapy studies, and these demonstrated a better safety profile than lumacaftor-ivacaftor. There appears to be additional benefit of changing to triple therapy for PwCF already established on ivacaftor."

Review • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2 | N=600 | Recruiting | Sponsor: University of North Carolina, Chapel Hill | Trial completion date: Jun 2023 ➔ Dec 2024 | Trial primary completion date: Jun 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Inhibition Of S-nitrosoglutathione Reductase Mitigates The Acute Injury In A Mouse Model Of Stroke (ISC 2023) - "The study shows the neuroprotective and functional recovery potential of orally administered N91115 through the inhibition of GSNOR. Based on the safety profile in humans, favorable pharmacokinetics and neuroprotective efficacy in an animal model of stroke, N91115 seems to be an ideal small molecule drug to be investigated in stroke patients."

Preclinical • Cardiovascular

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del) (BTS WM 2022) - "Two authors then independently extracted data, assessed risk of bias and evidence quality (GRADE).Results A total of 34 RCTs were included (1754 participants); eight monotherapy RCTs (4PBA, CPX, lumacaftor, cavosonstat and FDL 169), fifteen dual-therapy RCTs (lumacaftor-ivacaftor or tezacaftor-ivacaftor) and eleven triple-therapy RCTs (elexacaftor-tezacaftor-ivacaftor, VX-659- tezacaftor-ivacaftor, VX-440-tezacaftor-ivacaftor and VX-152-tezacaftor-ivacaftor). There were significant and clinically relevant differences found across outcomes in the triple therapy studies, with improved safety profile. More research is needed into assessing these therapies in paediatric patients and the longer-term safety profiles of these new therapies, but these early results suggest this will be a transformational intervention for pwCF with class 2 CFTR gene variants."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pediatrics • Pulmonary Disease • Respiratory Diseases • CFTR

Iron Single Atom Catalyzed Quinoline Synthesis. (PubMed, Adv Mater) - "Particularly, a Cavosonstat derivative can be synthesized through a one-step, Fe -catalyzed cyclization instead of traditional Suzuki coupling. The strategy is also applicable to the deuteration of quinolines at the fourth position, which is challenging by conventional methods. The synthetic utility of the carbon-based SAC, together with its reusability and scalability, renders it promising for industrial scale catalysis."

Journal

New research aims to improve treatments and outcomes for people with severe asthma (Eurekalert) - "The Precision Interventions for Severe and/or Exacerbation-Prone Asthma Network (PrecISE) study...is enrolling patients at Cleveland Clinic and University Hospitals Rainbow Babies & Children's Hospital....Cleveland Clinic aims to enroll 35 adult patients and University Hospitals Rainbow Babies & Children's Hospital aims to enroll eight pediatric patients....The phase 2, randomized crossover study will evaluate the effectiveness of six experimental therapies to treat severe asthma.These therapies will include medium chain triglyceride supplementation, clazakizumab, broncho-vaxom, imatinib mesylate, cavosonstat and itacitinib."

Trial status • Asthma • Immunology • Respiratory Diseases

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). (PubMed, Cochrane Database Syst Rev) - "There is insufficient evidence that corrector monotherapy has clinically important effects in pwCF with F508del/F508del. Both dual therapies (lumacaftor-ivacaftor, tezacaftor-ivacaftor) result in similar improvements in QoL and respiratory function with lower pulmonary exacerbation rates. Lumacaftor-ivacaftor was associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (not observed for tezacaftor-ivacaftor). Tezacaftor-ivacaftor has a better safety profile, although data are lacking in children under 12 years. In this population, lumacaftor-ivacaftor had an important impact on respiratory function with no apparent immediate safety concerns; but this should be balanced against the blood pressure increase and shortness of breath seen in longer-term adult data when considering lumacaftor-ivacaftor. There is high-quality evidence of clinical efficacy with probably little or no difference in AEs for triple..."

Journal • Review • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2; N=800; Recruiting; Sponsor: University of North Carolina, Chapel Hill; Active, not recruiting ➔ Recruiting

Enrollment open • Asthma • Respiratory Diseases

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Cavosonstat Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Subjects With Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P2; N=108; Not yet recruiting; Sponsor: GSNOR Therapeutics, Inc.

Clinical • New P2 trial • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

SNO-7: Study of Cavosonstat (N91115) in CF Patients Who Are Heterozygous for F508del-CFTR and a Gating Mutation and Being Treated With Ivacaftor (clinicaltrials.gov) - P2; N=19; Active, not recruiting; Sponsor: Nivalis Therapeutics, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Fibrosis • Immunology

MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects (clinicaltrials.gov) - P1; N=49; Completed; Sponsor: Nivalis Therapeutics, Inc.; Active, not recruiting -> Completed

Trial completion • Biosimilar

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2; N=800; Active, not recruiting; Sponsor: University of North Carolina, Chapel Hill; Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Respiratory Diseases

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2; N=800; Recruiting; Sponsor: University of North Carolina, Chapel Hill; Not yet recruiting ➔ Recruiting

Enrollment open

PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study (clinicaltrials.gov) - P2; N=800; Not yet recruiting; Sponsor: University of North Carolina, Chapel Hill

New P2 trial