tozorakimab (MEDI3506) / AstraZeneca - LARVOL DELTA

An Accessorised Prefilled Syringe to an Autoinjector Pharmacokinetic Bridging Study of Tozorakimab (clinicaltrials.gov) - P1 | N=254 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

COMETA: A Study to Investigate Efficacy and Safety of Tozorakimab Injections Compared With Placebo in Adult Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations and Elevated Eosinophils (clinicaltrials.gov) - P2 | N=98 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Tozorakimab: Data from P3 PROSPERO trial (NCT05742802) for COPD in H1 2026 (AstraZeneca) - Q3 2025 Results: Data from P2 UMBRIEL trial (NCT06932263) for uncontrolled asthma post 2026

P2 data • P3 data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology

IL-31/33 Axis in Atopic Dermatitis. (PubMed, Int J Mol Sci) - "Targeting the IL-31/IL-33 axis represents an emerging therapeutic option, e.g., nemolizumab (anti-IL-31RA) significantly reduces pruritus and AD symptoms in clinical trials. However, anti-IL-33/ST2 agents (e.g., etokimab, tozorakimab) demonstrate variable efficacy, highlighting complexity in targeting IL-33. Future research should prioritize biomarker-driven patient stratification to optimize the clinical application of these novel antibody-based therapies."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • CD123 • FLG • IL13 • IL31RA • IL33 • IL4 • IL5

ERJ- A phase 2a trial of the IL-33 monoclonal antibody tozorakimab in patients with COPD: FRONTIER-4, incl. discussion and QA (ERS 2025) - "Selected as an important RCT with interesting results recently published in the ERJ"

Clinical • P2a data • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases • IL33

Tozorakimab exerts distinct dual pharmacology to reduce COPD epithelial remodelling (ERS 2025) - " Tozorakimab was the only anti-IL-33/ST2 mAb, including itepekimab and astegolimab, that reduced mucus secretion in differentiated, bronchial COPD ALI cultures ( Table ). Of the anti-IL-33/ST2 mAbs tested, only tozorakimab demonstrated the ability to reduce epithelial remodelling and promote repair. Tozorakimab is under clinical investigation in COPD and other respiratory diseases."

Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases • IL33 • MUC5AC

Airway IL-33 levels are similar in current and former smokers with stable or exacerbating COPD (ERS 2025) - P3 | "Comparable airway IL-33 levels were observed in CS and FS with stable or exacerbating COPD. Results suggest potential benefits of inhibiting IL-33 red and IL-33 ox activity in CS and FS with COPD. Tozorakimab, an anti-IL-33 mAb with a dual mechanism of action inhibiting IL-33 red and IL-33 ox activity, is being investigated in Ph 3 studies in COPD (NCT05166889, NCT05158387, NCT06040086, NCT05742802)."

Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases • IL3 • IL33

Phase 3 studies evaluating the efficacy and safety of tozorakimab in COPD: OBERON and TITANIA study designs [WITHDRAWN] (ERS 2025) - No abstract available

Clinical • P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

A phase 3 extension study evaluating long-term efficacy and safety of tozorakimab in COPD: PROSPERO study design [WITHDRAWN] (ERS 2025) - No abstract available

Clinical • P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

Multi-Criteria Decision Analysis of Biologics in Chronic Obstructive Pulmonary Disease. (PubMed, Int J Chron Obstruct Pulmon Dis) - "Dupilumab (anti-IL-4Rα) demonstrated the most robust efficacy in eosinophilic COPD, with consistent reductions in exacerbation rates and improvements in FEV1, supported by high trial quality. Mepolizumab and benralizumab (anti-IL-5/IL-5R) showed moderate efficacy in biomarker-enriched populations. Anti-alarmins, specifically tozorakimab (anti-IL-33), itepekimab (anti-IL-33/IL-1RL1), astegolimab (anti-ST2), and tezepelumab (anti-TSLP), showed mixed results, with modest lung function gains but largely non-significant effects on exacerbation rates. Agents targeting non-T2 pathways, including infliximab (anti-TNF-α), canakinumab (anti-IL-1β), MEDI8968 (anti-IL-1R1), CNTO6785 (anti-IL-17A), and ABX-IL8 (anti-IL-8), consistently failed to demonstrate clinical efficacy, often due to small sample sizes, early-phase design, and lack of biomarker stratification. Biologics targeting T2 inflammation offer therapeutic promise in eosinophilic COPD when guided by biomarkers...."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL17A • IL1B • IL1R1 • IL33 • IL5

Breaking new ground biologic in COPD: Beyond the usual puff (MTS 2025) - "The most significant advancement is the FDA approval of dupilumab, an anti-IL-4/IL-13 monoclonal antibody, for COPD patients with type 2 inflammation...Other biologics under investigation include anti-IL-5 agents like mepolizumab and benralizumab, which target eosinophilic inflammation, and anti-alarmins such as itepekimab, astegolimab, tozorakimab and tezepelumab, which interfere with epithelial-derived cytokines like IL-33 and TSLP...Biomarkers such as blood eosinophil count, FeNO, and mucus scoring techniques (CT-based and bronchoscopic) are becoming essential tools in identifying candidates for biologic therapy. This biologic revolution signals a departure from standard inhaler-based regimens, offering a new frontier in COPD management where therapy is matched to inflammatory phenotype—marking a bold step forward in precision respiratory medicine."

Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases • IL13 • IL33 • IL4 • IL5 • TSLP

An Accessorised Prefilled Syringe to an Autoinjector Pharmacokinetic Bridging Study of Tozorakimab (clinicaltrials.gov) - P1 | N=235 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

Tozorakimab: Data from P3 OBERON trial (NCT05166889) for COPD in H1 2026 (AstraZeneca) - H1 & Q2 2025 Results: Data from P3 TITANIA trial (NCT05158387) for COPD in H1 2026

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

Tozorakimab: Data from P3 PROSPERO trial (NCT05742802) for COPD in H2 2026 (AstraZeneca) - H1 & Q2 2025 Results: Data from P3 MIRANDA trial (NCT06040086) in adults with symptomatic COPD with a history of exacerbations in H1 2026

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

Safety Profile of Tozorakimab (an Anti-IL-33 Monoclonal Antibody): Data From the FRONTIER Phase 2 Program of 1076 Patients (ATS 2025) - P2, P3 | "Across all four FRONTIER studies, tozorakimab was well tolerated with no safety concerns identified. Several phase 3 studies are ongoing for tozorakimab in COPD (NCT05166889, NCT05158387, NCT06040086 and NCT05742802) and severe viral lower respiratory tract disease (NCT05624450)."

Clinical • P2 data • Asthma • Atopic Dermatitis • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Dermatitis • Dermatology • Diabetic Nephropathy • Heart Failure • Immunology • Inflammation • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases • IL33

New data for Airsupra and Breztri highlight progress in advancing asthma and COPD care globally (AstraZeneca Press Release) - "AstraZeneca will present the latest clinical and real-world data across its leading inhaled, biologic and early science respiratory portfolio at the American Thoracic Society (ATS) International Conference, in San Francisco, CA from 16 to 21 May 2025...With more than 75 abstracts, including eight late-breakers, the Company continues to drive innovation and address unmet needs in care across all severities of asthma, chronic obstructive pulmonary disease (COPD), eosinophilic granulomatosis with polyangiitis (EGPA) and other chronic inflammatory diseases."

Clinical data • Asthma • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Eosinophilic Granulomatosis With Polyangiitis • Inflammation

An Accessorised Prefilled Syringe to an Autoinjector Pharmacokinetic Bridging Study of Tozorakimab (clinicaltrials.gov) - P1 | N=252 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

COMETA: A Study to Investigate Efficacy and Safety of Tozorakimab Injections Compared With Placebo in Adult Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations and Elevated Eosinophils (clinicaltrials.gov) - P2 | N=98 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Tozorakimab: Data from P2 UMBRIEL trial (NCT06932263) for uncontrolled asthma post 2026 (AstraZeneca) - Q1 2025 Results

P2 data • Asthma • Immunology

Umbriel: Dose Range Finding Study to Assess Efficacy and Safety of Tozorakimab in Adults With Uncontrolled Asthma on Medium-to-High Dose Inhaled Corticosteroids (clinicaltrials.gov) - P2 | N=540 | Recruiting | Sponsor: AstraZeneca

New P2 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

OBERON: Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations (clinicaltrials.gov) - P3 | N=1132 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

TITANIA: Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations. (clinicaltrials.gov) - P3 | N=1172 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

An Accessorised Prefilled Syringe to an Autoinjector Pharmacokinetic Bridging Study of Tozorakimab (clinicaltrials.gov) - P1 | N=252 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

A phase 2a trial of the IL-33 mAb tozorakimab in patients with COPD: FRONTIER-4. (PubMed, Eur Respir J) - P2 | "Although the primary endpoint was not met in the intent-to-treat population, tozorakimab showed positive efficacy signals versus placebo in a subgroup of patients with COPD with a high risk of exacerbations."

Clinical • Journal • P2a data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL33

COMETA: A Study to Investigate Efficacy and Safety of Tozorakimab Injections Compared With Placebo in Adult Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations and Elevated Eosinophils (clinicaltrials.gov) - P2 | N=98 | Not yet recruiting | Sponsor: AstraZeneca

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