glasmacinal (EP395) / EpiEndo Pharma - LARVOL DELTA

EP395, a novel non-antibiotic macrolide, enhances antiviral responses in bronchial epithelial cells from asthma patients (BTS WM 2025) - "ALOX15 is involved in synthesis of RvD1 during the early stages of bacterial infection in COPD MDMs, which may explain why patients with viral AECOPD experience worse symptoms and delayed recovery. Work is ongoing to determine the effects of RvD1 on virus-infected MDMs."

Clinical • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Inflammation • Influenza • Pulmonary Disease • Respiratory Diseases • ALOX15 • CSF2 • CXCL8 • FPR2 • IL10 • IL6 • STAT3

Clinical Trial Investigating the Effects of EP395 Following an Inhaled Endotoxin Challenge in Healthy Adults (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: EpiEndo Pharmaceuticals | Recruiting ➔ Completed | N=65 ➔ 40 | Trial completion date: Jun 2026 ➔ Aug 2025 | Trial primary completion date: Jun 2026 ➔ Aug 2025

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

A novel macrolide, EP395, with reduced antibacterial activity and an enhancing effect on respiratory epithelial barrier. (PubMed, Pulm Pharmacol Ther) - "Acute exacerbations are often treated with macrolides, including azithromycin (AZM). In mice exposed to sulphur dioxide, pre-treatment with EP395 reduced extravasation of human serum albumin into the bronchoalveolar lavage fluid. These data demonstrate epithelial barrier-protecting effects of EP395, a promising candidate for treatment of chronic respiratory diseases without risk of bacterial resistance."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Effect of EP395, a novel anti-inflammatory macrolide, in an inhaled lipopolysaccharide challenge model in healthy volunteers: a randomised controlled trial. (PubMed, Pulm Pharmacol Ther) - "The log2 transformed fold difference in the EP395 group, before and 24 hours after LPS challenge was 0.33 (95 % CI 0.52, 0.14; p=0.0007). EP395 treatment increased the host defence response to inhaled LPS, including the epithelial response, whilst reducing inflammatory site pro-inflammatory mediators."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CCL4 • CXCL8 • ELANE • IL1B • IL33 • IL6 • MPO • TNFA

Effects of EP395, a novel macrolide, on acute neutrophilic airway inflammation. (PubMed, Pulm Pharmacol Ther) - "EP395 had comparable inhibitory effects to azithromycin in all three models. The PDE4 inhibitor, roflumilast, was also included as a positive control in the LPS model, with comparable effects on neutrophil numbers. In vitro assays on neutrophil function revealed both stimulatory and inhibitory effects of treatment with EP395. These data demonstrate the beneficial pharmacological activity of EP395, a macrolide with negligible antimicrobial activity, in models of acute neutrophilic inflammation and on neutrophil activity and supported its progression into clinical development as a potential treatment for COPD."

Journal • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Clinical Trial Investigating the Effects of EP395 Following an Inhaled Endotoxin Challenge in Healthy Adults (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: EpiEndo Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open

Clinical Trial Investigating the Effects of EP395 Following an Inhaled Endotoxin Challenge in Healthy Adults (clinicaltrials.gov) - P1 | N=65 | Not yet recruiting | Sponsor: EpiEndo Pharmaceuticals

New P1 trial

EpiEndo reports Phase 2A results for lead asset, EP395, in COPD (Businesswire) - P2a | N=37 | NCT05572333 | Sponsor: EpiEndo Pharmaceuticals | "EpiEndo Pharmaceuticals...announces the successful completion of its Phase 2A clinical trial for EP395 in patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD)....With the global cost of COPD estimated to rise to $4.8 trillion by 2030, there is a vital unmet need for new and improved therapeutics....EpiEndo’s Phase 2A study investigated the safety and tolerability of EP395 administered once-daily as oral capsules to COPD patients for 12 weeks. In addition, it assessed the effect of EP395 on a number of biomarkers. 61 adults diagnosed with COPD were enrolled in the study across six clinics in the UK and Germany....The study results show EP395 to have tolerability and safety as well as beneficial effects on inflammatory biomarkers, as seen with antibiotic macrolides."

Biomarker • P2a data • Pricing • Chronic Obstructive Pulmonary Disease

Clinical Trial to Assess Effect of Verapamil on Systemic Exposure of EP395 and Effect of EP395 on Systemic Exposure of Midazolam and Digoxin (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: EpiEndo Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Clinical Trial to Investigate the Safety and Tolerability of EP395 in Patients With COPD (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: EpiEndo Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Clinical Trial to Assess Effect of Verapamil on Systemic Exposure of EP395 and Effect of EP395 on Systemic Exposure of Midazolam and Digoxin (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: EpiEndo Pharmaceuticals

New P1 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Clinical Trial to Investigate the Safety and Tolerability of EP395 in Patients With COPD (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: EpiEndo Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CRP • CST3 • ELANE • IL10 • IL23A • IL33 • IL6 • MMP9 • MPO

Clinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults (clinicaltrials.gov) - P1 | N=49 | Completed | Sponsor: EpiEndo Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CCL2 • CRP • CXCL8 • IL10 • IL23A • IL33 • IL6

Clinical Trial to Investigate the Safety and Tolerability of EP395 in Patients With COPD (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: EpiEndo Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CRP • CST3 • ELANE • IL10 • IL23A • IL33 • IL6 • MMP9 • MPO

EpiEndo commences Phase 2a trial for EP395 in COPD patients (Businesswire) - "EpiEndo Pharmaceuticals...has received regulatory approval to commence a Phase 2a clinical trial with lead molecule EP395 in COPD (Chronic Obstructive Pulmonary Disease) patients. EP395 is an orally available macrolide or ‘Barriolide™,’ with reduced antimicrobial resistance potential, which aims to address the unmet medical need for a treatment for COPD....The results of the study are expected in H2 2023 and will provide key data on EP395 in a COPD population."

P2a data • Trial status • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Clinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: EpiEndo Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CCL2 • CRP • CXCL8 • IL10 • IL23A • IL33 • IL6

Clinical Trial to Investigate the Safety and Tolerability of EP395 in Patients With COPD (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: EpiEndo Pharmaceuticals

New P2 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CRP • CST3 • ELANE • IL10 • IL23A • IL33 • IL6 • MMP9 • MPO

EpiEndo commences LPS challenge trial for lead candidate EP395 (Businesswire) - "EpiEndo Pharmaceuticals...has received regulatory and ethics approval to commence a Lipopolysaccharide (LPS) challenge clinical trial with lead molecule EP395....The study will be conducted in up to 48 healthy adults at the Hannover Medical School in Germany....'We look forward to the valuable data that it will generate which will be key as we plan the next phase of clinical development.'"

New P1 trial • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

"EpiEndo commences LPS challenge trial for lead candidate EP395 https://t.co/an3EkRExZt" (@NewsFromBW)

Clinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: EpiEndo Pharmaceuticals

New P1 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CCL2 • CRP • CXCL8 • IL10 • IL23A • IL33 • IL6

"EpiEndo: Successful Completion of Phase I Study for Lead Asset EP395 https://t.co/1YC6UwJlki" (@NewsFromBW)

Single and Multiple Ascending Dose Study With EP395 (clinicaltrials.gov) - P1 | N=78 | Completed | Sponsor: EpiEndo Pharmaceuticals | Recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Mar 2022 | Trial primary completion date: Dec 2021 ➔ Mar 2022

Trial completion • Trial completion date • Trial primary completion date

EpiEndo Pharmaceuticals Secures EUR 20 Million Series A Funding to Advance Clinical Development of its Non-Antibiotic Macrolide for the treatment of COPD (Businesswire) - "EpiEndo Pharmaceuticals...announces the closing of a €20m Series A financing round led by Flerie Invest and Iðunn Venture Fund, with existing investors ABC Ventures participating, along with the European Innovation Council (EIC) Fund joining the round. The financing secures funds to advance clinical development of EpiEndo’s lead compound EP395, which entered phase I clinical trials in April, through Phase IIa, targeting COPD as a primary indication....Using this Series A funding, EpiEndo aims to advance the clinical development of EP395 towards approval as the first disease modifying non-antibiotic macrolide that can be prescribed safely and effectively as a long-term treatment for patients with COPD."

Financing • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Single and Multiple Ascending Dose Study With EP395 (clinicaltrials.gov) - P1; N=78; Recruiting; Sponsor: EpiEndo Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

EpiEndo Pharmaceuticals Announces Launch of First-in-Human Clinical Trial of a Non-Antibiotic Macrolide for the Treatment of Chronic Inflammatory Airway Diseases (Businesswire) - "EpiEndo Pharmaceuticals...announced today that the first subjects have been dosed in the Company's first-in-human phase I clinical trial of its lead candidate, EP395, at the Medicines Evaluation Unit (MEU) in Manchester...'I am delighted to say that our single ascending dose study has started and that the first six healthy subjects have been given a dose of EP395,'...Dosing of our first subjects with EP395 is an important milestone for EpiEndo, as it brings us one step closer to offering a potentially meaningful therapeutic option to patients with COPD."

Trial status • Chronic Obstructive Pulmonary Disease • Respiratory Diseases