opelconazole (PC945) / Pulmocide - LARVOL DELTA

Novel antifungal opelconazole showed no evidence of inducing a proinflammatory response following inhalation delivery for 12 weeks (ERS 2025) - No abstract available

Inflammation

Can Inhaled Antifungals Provide a Viable Solution for Treatment-Refractory Pulmonary Fungal Infections? (PubMed, Expert Rev Anti Infect Ther) - No abstract available

Journal • Infectious Disease

Successful treatment of an allergic bronchopulmonary aspergillosis patient with inhaled antifungal opelconazole. (PubMed, J Allergy Clin Immunol Pract) - No abstract available

Journal • Allergic Bronchopulmonary Aspergillosis • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Antifungal pipeline: New tools for the treatment of mycoses. (PubMed, Rev Iberoam Micol) - "New antifungal agents, such as ibrexafungerp, rezafungin, oteseconazole, and miltefosine, offer novel mechanisms of action along with reduced toxicity...This review provides a comprehensive overview of these new agents and their mechanisms, and explores the challenges and roles of antifungal drugs in LMICs, where the burden of fungal infections is high. Continued research and development are essential to address the rising incidence and resistance of fungal infections globally."

Journal • Dermatology • Infectious Disease

An update on newer antifungals. (PubMed, Expert Rev Anti Infect Ther) - "New antifungal agents hold promising future for difficult-to-treat fungal infections, providing for improved bioavailability, pharmacokinetic properties, adverse events and drug interactions, as well as, spectrum of activity. However, further data is needed before incorporating these agents in everyday clinical practice for the management of invasive fungal infections."

Journal • Review • Candidiasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Safety and Efficacy of PC945 (Opelconazole) in Combination With Other Antifungal Therapy for the Treatment of Refractory Invasive Pulmonary Aspergillosis (OPERA-T Study) (clinicaltrials.gov) - P3 | N=123 | Recruiting | Sponsor: Pulmocide Ltd | Trial completion date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Nov 2025 ➔ Mar 2026

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

Safety and Efficacy of PC945 (Opelconazole) in Combination With Other Antifungal Therapy for the Treatment of Refractory Invasive Pulmonary Aspergillosis (OPERA-T Study) (clinicaltrials.gov) - P3 | N=123 | Recruiting | Sponsor: Pulmocide Ltd | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Nov 2025

Combination therapy • Trial completion date • Trial primary completion date • Pulmonary Disease • Respiratory Diseases

New and emerging roles for inhalational and direct antifungal drug delivery approaches for treatment of invasive fungal infections. (PubMed, Expert Rev Anti Infect Ther) - "Novel compounds (e.g. opelconazole) and existing antifungals with innovative drug delivery systems currently undergoing clinical trials and/or used off-label in the clinical setting are discussed. For both inhalational agents and direct delivery approaches, there are similar challenges that include the absence of: approved formulations for specific administration routes, delivery vehicles that are simple and safe to use whilst maintaining potency and efficiency of delivery, animal models suitable for investigating pharmacokinetic/pharmacodynamic profiles of inhaled antifungals, and consensus on the composite endpoints and intervals for of follow-up in clinical trials. To meet these challenges, cooperation of all stakeholders in drug development and regulation is required."

Journal • Review • Infectious Disease

Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric Perspective. (PubMed, J Pediatric Infect Dis Soc) - "The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin. Additionally, key drug attributes of these novel agents and their potential future therapeutic roles in pediatric transplant recipients are discussed."

Journal • Infectious Disease • Pediatrics • Transplantation

New treatment options for critically important WHO fungal priority pathogens. (PubMed, Clin Microbiol Infect) - "While the limited number of targets and the emergence of resistance have posed challenges to antifungal treatment, new drugs such as ibrexafungerp, rezafungin, fosmanogepix, or olorofim have shown promising clinical efficacy. These drugs not only provide alternative options for invasive fungal infections but also alleviate treatment in outpatient settings. More clinical data, implementation of stewardship programs, and surveillance, including utilization of drugs in agriculture are necessary to prevent resistance development and ensure the safety and efficacy of these new agents."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Antifungal Therapies for Aspergillus spp.: Present and Future. (PubMed, Semin Respir Crit Care Med) - "Rezafungin (a once-weekly dosed echinocandin) and ibrexafungerp (oral agent with same mechanism of action as echinocandins) will likely be reserved for combination therapy or refractory/intolerance scenarios with no other options. Inhaled opelconazole is an attractive option for combination therapy and prophylaxis of pulmonary aspergillosis...Finally, olorofim and fosmanogepix, two agents with novel mechanisms of action and oral formulations, hold significant potential to challenge the triazole antifungals place as preferred therapies. However, many questions remain regarding these novel agents, and at the time of this writing, none of these agents have been robustly studied in Phase III studies of aspergillosis, and so their promise remains investigational."

Journal • Pulmonary Disease • Respiratory Diseases

Safety and Efficacy of PC945 (Opelconazole) in Combination With Other Antifungal Therapy for the Treatment of Refractory Invasive Pulmonary Aspergillosis (clinicaltrials.gov) - P3 | N=123 | Recruiting | Sponsor: Pulmocide Ltd | Trial completion date: Nov 2023 ➔ Apr 2025 | Trial primary completion date: Oct 2023 ➔ Mar 2025

Combination therapy • Trial completion date • Trial primary completion date • Pulmonary Disease • Respiratory Diseases

A Safety Study of PC945 (Opelconazole) Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients (clinicaltrials.gov) - P2 | N=102 | Completed | Sponsor: Pulmocide Ltd | Active, not recruiting ➔ Completed

Trial completion • Pulmonary Disease • Respiratory Diseases • Transplantation

PC945 (OPELCONAZOLE) NEBULIZER SUSPENSION - a new inhaled antifungal in development for pulmonary aspergillosis (IDWeek 2023) - No abstract available

Infectious Disease

Anti-infective treatment of fungal infections by Candida and Aspergillus (PubMed, Med Klin Intensivmed Notfmed) - "Knowledge about risk factors and the correct treatment management is crucial for the survival of patients with invasive fungal infections."

Journal • Review • Candidiasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Emerging Diagnostics and Therapeutics for Invasive Fungal Infections. (PubMed, Infect Dis Clin North Am) - "Compared with traditional fungal diagnostics, molecular assays promise improved sensitivity and specificity, the ability to test a range of samples (including noninvasive samples, ie, blood), the detection of genetic mutations associated with antifungal resistance, and the potential for a faster turnaround time. Antifungals in late-stage clinical development include agents with novel mechanisms of action (olorofim and fosmanogepix) and new members of existing classes with distinct advantages over existing antifungals in toxicity, drug-drug interactions, and dosing convenience (oteseconazole, opelconazole, rezafungin, ibrexafungerp, encochleated amphotericin B)."

Journal • Review • Infectious Disease • Transplantation

PC945 Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Pulmocide Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Pulmonary Disease • Respiratory Diseases • Transplantation

Discovery of PC945, a novel antifungal agent for inhaled administration (ACS-Fall 2023) - "In temporarily neutropenic, immunocompromised mice infected with A. fumigatus, half of the animals survived until day 7 when treated intranasally with PC945 at 0.56 μg/mouse.In addition, clinical data under a special needs program will be presented using PC945 as part of a combination treatment for a refractory fungal bronchial anastomotic infection and tracheobronchitis. In this setting, PC945 showed excellent tolerability profile and had promising efficacy in controlling the active infection."

Hepatology • Infectious Disease • Liver Failure • Pulmonary Disease • Respiratory Diseases • Solid Organ Transplantation • Transplantation

Treatment of Invasive Aspergillosis: How It's Going, Where It's Heading. (PubMed, Mycopathologia) - "Promising new drugs for the treatment of IA are in late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix (a Gwt1 enzyme inhibitor), ibrexafungerp (a triterpenoid), opelconazole (an azole optimized for inhalation) and rezafungin (an echinocandin with long half-life time). Current investigations show encouraging results, so far mostly in preclinical settings. In this review we discuss current treatment strategies, give an outlook on possible new pharmaceutical therapeutic options, and, lastly, provide an overview of the ongoing research in immunotherapy for IA."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases

The antifungal pipeline for invasive fungal diseases: what does the future hold? (PubMed, Expert Rev Anti Infect Ther) - "Areas covered: The current review will discuss the five promising antifungal agents for IFD (i.e. fosmanogepix, ibrexafungerp, olorofim, rezafungin and opelconazole), now in the late-phase clinical studies, and likely to be available for clinical use in the near future. There are unmet needs of these novel agents that should be addressed in the future studies. These include defining their indications and benefits, how to best target them appropriately, surveillance and stewardship of their use."

Journal • Infectious Disease

Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review. (PubMed, J Fungi (Basel)) - "These included new additions to existing antifungal classes (rezafungin and opelconazole), first-in-class drugs such as ibrexafungerp, manogepix/fosmanogepix, olorofim and tetrazoles (quilseconazole, oteseconazole and VT-1598), as well as other innovative agents like ATI-2307, MGCD290 and VL-2397. All these compounds demonstrated significant improvements in survival and reduction in tissue fungal burden on neutropenic animal models of candidemia due to C. auris. Continual efforts towards the discovery of new treatments against this multidrug-resistant fungus are essential."

Journal • Review • Infectious Disease

"And novel antifungals to be featured #IDWeek2022: opelconazole, ibrexafungerp, MAT2203, oloforim, rezafungin, and oteseconazole @IDSAInfo @SuperBugDoc @FungalDoc @GermHunterMD @DrPappasID @tmhohl71 @martinhoenigl @davidrandes @JessicaLittleMD" (@LionakisLab)

Infectious Disease

PC945 (opelconazole) Nebulizer Suspension (IDWeek 2022) - No abstract available

Infectious Disease

PC945 Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Pulmocide Ltd | Trial completion date: Jul 2022 ➔ Nov 2023 | Trial primary completion date: Jul 2022 ➔ Nov 2023

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

Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents. (PubMed, J Fungi (Basel)) - "Several new antifungals are currently in late-stage development, including those with novel pharmacodynamics/mechanisms of action that represent new antifungal classes (manogepix, olorofim, ATI-2307, GR-2397). Others include new agents within established classes or with mechanisms of action similar to clinically available antifungals (ibrexafungerp, rezafungin, oteseconazole, opelconazole, MAT2203) that have been modified in order to improve certain characteristics, including enhanced pharmacokinetics and greater specificity for fungal targets...The tolerability and drug-drug interaction profiles of these new agents also appear to be promising, although the number of human subjects that have been exposed to many of these agents remains relatively small. Overall, these agents have the potential for expanding our antifungal armamentarium and improving clinical outcomes in patients with invasive mycoses."

Journal • PK/PD data • Review • Dermatology