ascorbic acid/bicarbonate/glutathione inhalation (Arina-1) / Renovion - LARVOL DELTA

ARINA-1 Improves Quality of Life in a Pilot Study of Chronic Bronchitis (ATS 2025) - "ARINA-1 is a buffered fixed dose combination therapy of ascorbic acid and reduced glutathione that is nebulized twice daily via an Investigational PARI eFlow nebulizer...Overall, ARINA-1 demonstrated a strong safety profile in patients with CB and improved quality of life and decreased cough frequency. These data demonstrate the need for further study of the use of ARINA-1 in CB."

Clinical • HEOR • Bronchiectasis • Chronic Cough • Chronic Obstructive Pulmonary Disease • Cough • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Study to Evaluate ARINA-1 in the Prevention of Bronchiolitis Obliterans Progression in Participants With Bilateral Lung Transplant (clinicaltrials.gov) - P3 | N=100 | Recruiting | Sponsor: Renovion, Inc. | Trial completion date: Jun 2025 ➔ Nov 2026 | Trial primary completion date: Jan 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Pulmonary Disease • Respiratory Diseases • Transplantation

Bronchiectasis. (PubMed, Open Respir Arch) - "Interactome analysis therefore becomes a vital tool for pinpointing alterations during both stable phases and exacerbations. This array of innovative approaches has revolutionized the personalization of treatments, incorporating therapies such as inhaled mannitol or ARINA-1, brensocatib for anti-inflammatory purposes, and inhaled corticosteroids specifically for patients with eosinophilic bronchiectasis."

Journal • Review • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • ELANE

ARINA-1 demonstrates Improved quality of life in a Phase 2a, randomized, doubleblind, placebo-controlled study in Individuals with non-CF bronchiectasis (NCFBE) with excess mucus and cough (RVN-301) (WBC 2024) - No abstract available

Clinical • HEOR • P2a data • Bronchiectasis • Cough • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

An Investigator-initiated Study to Evaluate Safety and Efficacy of ARINA-1 in People With a Tracheostomy (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Matthew Bruehl | N=25 ➔ 0 | Trial completion date: Oct 2024 ➔ Sep 2023 | Recruiting ➔ Withdrawn | Trial primary completion date: Oct 2024 ➔ Sep 2023

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal

Renovion Announces Positive Top-Line Results from Phase 2 CLIMB Study of ARINA-1 (RVN-301) in Patients with Non-Cystic Fibrosis Bronchiectasis (Businesswire) - P2a | N=40 | CLIMB (NCT05495243) | Sponsor: Renovion, Inc "The trial was conducted at nine sites across the US. Participants were randomized (7:3, treatment:placebo), and 40 participants completed the study, with 29 completing in the ARINA-1 arm and 11 in the placebo (0.9% saline) arm. Topline results from the intention-to-treat (ITT) population demonstrate that ARINA-1 is safe and improves quality of life (QOL) in individuals with NCFBE who experience mucus symptoms...ARINA-1 was well-tolerated in individuals with NCFBE with mucus symptoms...Topline ITT efficacy results from the trial demonstrated that ARINA-1 improved quality of life in individuals with NCFBE at day 28...The topline exploratory analysis of sputum data indicated that ARINA-1 demonstrated improved mucus viscosity and sputum neutrophil elastase (NE) compared to placebo."

P2a data • Cough • Non‐Cystic Fibrosis Bronchiectasis

Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough (clinicaltrials.gov) - P2 | N=40 | Completed | Sponsor: Renovion, Inc. | Active, not recruiting ➔ Completed

Trial completion • Bronchiectasis • Cough • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Study to Evaluate ARINA-1 in the Prevention of Bronchiolitis Obliterans Progression in Participants With Bilateral Lung Transplant (clinicaltrials.gov) - P3 | N=100 | Recruiting | Sponsor: Renovion, Inc. | Trial completion date: Jul 2024 ➔ Jun 2025 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Pulmonary Disease • Respiratory Diseases • Transplantation

Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Renovion, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Bronchiectasis • Cough • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Renovion, Inc. | Phase classification: P2a ➔ P2

Phase classification • Bronchiectasis • Cough • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough (clinicaltrials.gov) - P2a | N=50 | Recruiting | Sponsor: Renovion, Inc. | Trial completion date: Sep 2023 ➔ Dec 2023 | Trial primary completion date: Sep 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Bronchiectasis • Cough • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CRP

Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough (clinicaltrials.gov) - P2a | N=50 | Recruiting | Sponsor: Renovion, Inc. | Trial completion date: Apr 2023 ➔ Sep 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Bronchiectasis • Cough • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CRP

First Patient Enrolled in Phase 3 Clinical Trial Evaluating ARINA-1 in Lung Transplant (Businesswire) - "Renovion, Inc. today announced that the first patient has been enrolled in a Phase 3 clinical study evaluating ARINA-1, an investigational nebulized therapy to prevent the progression of bronchiolitis obliterans syndrome (BOS) progression in individuals with a bilateral lung transplant....The Phase 3 study is a randomized, multicenter study evaluating the efficacy and safety of ARINA-1 in the prevention of BOS progression in individuals with a bilateral lung transplant. The study is expected to enroll approximately 100 participants across 15 sites in the US."

Trial status • Respiratory Diseases

Renovion Receives FDA Fast Track Designation for ARINA-1 for the Prevention of BOS Progression in Lung Transplant Patients (Businesswire) - "Renovion...announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ARINA-1 for the prevention of bronchiolitis obliterans syndrome (BOS) progression in adults with a bilateral lung transplant. The FDA grants Fast Track designation to facilitate the development and expedite the review of medicines to treat serious conditions and fill an unmet medical need. It allows for rolling submission of regulatory documentation to the FDA resulting in faster regulatory review. It is intended to expedite the review of promising medicines to facilitate a faster path to patients with a serious, unmet need....'We are pleased with the FDA's decision to grant Fast Track designation for ARINA-1 in bilateral lung transplant patients with early BOS, and we look forward to enrolling our first patient in the next few week.'"

Fast track designation • Trial status • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease

Mucociliary Clearance Augmenting Drugs Block SARS-Cov-2 Replication in Human Bronchial Epithelial Cells. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "Ultimately, we showed that improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that Intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study to Evaluate ARINA-1 in the Prevention of Bronchiolitis Obliterans Progression in Participants With Bilateral Lung Transplant (clinicaltrials.gov) - P3 | N=100 | Recruiting | Sponsor: Renovion, Inc.

New P3 trial • Pulmonary Disease • Respiratory Diseases • Transplantation

An Investigator-initiated Study to Evaluate Safety and Efficacy of ARINA-1 in People With a Tracheostomy (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Matthew Bruehl

New P1 trial

Renovion Announces First Patient Enrolled in Phase 2 Clinical Study Evaluating ARINA-1 for the Treatment of Non-CF Bronchiectasis (Businesswire) - "Renovion....announced that the first patient has been enrolled in a Phase 2 clinical study evaluating ARINA-1, an investigational nebulized therapy, to treat adults with non-CF bronchiectasis (NCFBE) (NCT05495243)....The objectives are to evaluate the safety and efficacy of ARINA-1 nebulized twice daily by adults with NCFBE who experience excess mucus and cough. The study is expected to enroll approximately 55 participants across nine sites in the US."

Trial status • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis

Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough (clinicaltrials.gov) - P2a | N=50 | Recruiting | Sponsor: Renovion, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Cough • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CRP

Phase 2a, 28-day Investigational Use Study of ARINA-1 in Non-CF Bronchiectasis With Excess Mucus and Cough (clinicaltrials.gov) - P2a | N=50 | Not yet recruiting | Sponsor: Renovion, Inc.

New P2a trial • Bronchiectasis • Cough • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CRP

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Mucociliary Transport Augmenting Agents Block SARS-Cov-2 Replication in Human Bronchial Epithelial Cells In Vitro (ATS 2022) - "Drugs evaluated included ivacaftor, camostat (via ENaC inhibition in addition to its antiviral effects), poly-N (acetyl, arginyl) glucosamine (PAAG), high molecular weight hyaluronic acid (HA), and ARINA-1 (consisting of glutathione, ascorbate and sodium bicarbonate). Ivacaftor had a slight effect on SARS-CoV-2 replication, but this occurred at concentrations close to its maximum solubility, unlikely to be relevant in vivo, thus we discontinued their study. Several MCT augmenting drugs have a significant inhibitory effect on SARS-CoV-2 replication in primary HBECs. MCT activating drugs may be potentially effective for anti-COVID treatment."

Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Renovion Provides Regulatory Update and Initiation of Clinical Program in Non-CF Bronchiectasis (Businesswire) - "Renovion, Inc...announced today that they have received a Study May Proceed Letter from the U.S. Food and Drug Administration (FDA) for a Phase 2 clinical trial to investigate ARINA-1 in non-cystic fibrosis bronchiectasis (NCFBE). 'We are excited to start participant recruitment for NCFBE trial in Q2 2022 and continue our clinical development with trials in lung transplant and non-tuberculosis mycobacteria pulmonary disease starting later this year'..."

IND • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

Renovion and the COPD Foundation Launch COPD and Bronchiectasis Development Partnership to Address Unmet Patient Need (Businesswire) - "Renovion and the COPD Foundation have announced the creation of a new partnership to accelerate the development of a novel therapy for the treatment of excessive airway mucus and inflammation in individuals with chronic obstructive pulmonary disease (COPD) and non-cystic fibrosis (CF) bronchiectasis. Phase 2 clinical trials are planned to begin in Q1 2022."

Licensing / partnership • New P2 trial • Chronic Obstructive Pulmonary Disease • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

Novel Therapy of Bicarbonate, Glutathione and Ascorbic Acid Improves Cystic Fibrosis Mucus Transport. (PubMed, Am J Respir Cell Mol Biol) - "Defective airway mucus clearance is a defining characteristic of cystic fibrosis lung disease, and improvements to current mucolytic strategies are needed. This response was absent in CFBE41o- F508del cells treated with VX-809 and primary HBE cells, implicating CFTR-independent mechanisms for the effect of ARINA-1 on CF mucus. Together, these studies indicate that ARINA-1 is a novel potential therapy for the treatment of impaired mucus clearance in CF."

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