tozorakimab (MEDI3506) / AstraZeneca - LARVOL DELTA

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

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 | Not yet recruiting | Sponsor: AstraZeneca

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

Safety Profile of Tozorakimab (an Anti-IL-33 Monoclonal Antibody): Data From the FRONTIER Phase 2 Program of 1076 Patients (ATS 2025) - No abstract available

Clinical • P2 data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL33

MIRANDA: Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations (clinicaltrials.gov) - P3 | N=1240 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2026 ➔ May 2026 | Trial primary completion date: Jun 2026 ➔ Mar 2026

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Tozorakimab: Data from P3 PROSPERO trial (NCT05742802) for COPD in 2026 (AstraZeneca) - Q4 & FY2024 Results: Data from P3 MIRANDA trial (NCT06040086) in adults with symptomatic COPD with a history of exacerbations in 2026

P3 data • Chronic Obstructive Pulmonary Disease

Tozorakimab: Data from P3 OBERON trial (NCT05166889) for COPD in 2026 (AstraZeneca) - Q4 & FY2024 Results: Data from P3 TITANIA trial (NCT05158387) for COPD in 2026

P3 data • Chronic Obstructive Pulmonary Disease

TILIA: Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen (clinicaltrials.gov) - P3 | N=2870 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2025 ➔ Jun 2026 | Trial primary completion date: Mar 2025 ➔ Jun 2026

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

FRONTIER-4: a phase 2a study to investigate tozorakimab (anti-IL-33 mAb) in COPD (BTS WM 2024) - P2 | "Tozorakimab was well tolerated. Conclusion Tozorakimab may improve lung function and reduce COPD exacerbations, especially in patients with frequent exacerbation history."

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

Tozorakimab: Data from P3 OBERON trial (NCT05166889) for COPD post 2025 (AstraZeneca) - Q3 2024 Results: Data from P3 TITANIA trial (NCT05158387) for COPD post 2025

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

FRONTIER-3: a randomized, phase 2a study to evaluate the efficacy and safety of tozorakimab (an anti-interleukin-33 monoclonal antibody) in early-onset asthma (BTS WM 2024) - P2 | "A trend towards greater numerical improvements was observed for the tozorakimab 600 mg dose compared with the 300 mg dose for several endpoints. View this table: View inline View popup Abstract S90 Table 1 Efficacy endpoints in the ITT population and patients with at least two exacerbations in previous 12 months"

Clinical • P2a data • Asthma • Immunology • Respiratory Diseases • IL33

Tozorakimab: Data from P3 PROSPERO trial (NCT05742802) for COPD post 2025 (AstraZeneca) - Q3 2024 Results: Data from P3 MIRANDA trial (NCT06040086) in adults with symptomatic COPD with a history of exacerbations post 2025

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

Efficacy and safety of tozorakimab in moderate-to-severe atopic dermatitis: A Phase 2a randomized controlled trial (FRONTIER-2). (PubMed, J Eur Acad Dermatol Venereol) - P2 | "FRONTIER-2 did not show a statistically significant difference in the primary endpoint for tozorakimab compared with placebo. However, numerical increases in responder rates were observed."

Journal • P2a data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • IL33

Tozorakimab (anti-IL-33 mAb) reduces mucus plugging in COPD: an imaging sub-study in the FRONTIER-4 phase 2a COPD trial (BTS WM 2024) - P2, P3 | "Conclusion This exploratory study offers the first insights into the effect of tozorakimab on mucus plugging in COPD, using CT imaging. Ongoing phase 3 studies ( NCT05166889 , NCT05158387 , NCT06040086 ) provide further opportunity to investigate the effect of tozorakimab on mucus plugging and the impact on symptoms, quality of life and lung function."

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

Inhibition of IL-33 by tozorakimab in patients with diabetic kidney disease: Cardiovascular insights from FRONTIER-1 (AHA 2024) - P2 | "Trends in BNP and sST2 over time were comparable.ConclusionThis study suggests a favorable cardiac safety profile for tozorakimab in patients with DKD. IL-33 inhibition did not elevate serum sST2 significantly."

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Heart Failure • Inflammation • Nephrology • Renal Disease • IL33

CDSCO Panel Approves AstraZeneca's Protocol Amendment Proposal For Tozorakimab Study (Medical Dialogues) - "The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has approved AstraZeneca's proposal for protocol amendment of the clinical trial....This came after the firm presented protocol no. D9180C00012, amendment version 2.0 dated 12 Jun 2024. The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab administered subcutaneously (SC) in adult participants with symptomatic COPD with a history of ≥ 2 moderate or ≥ 1 severe exacerbation of COPD in the 12 months prior to enrolment."

Non-US regulatory • Chronic Obstructive Pulmonary Disease • Immunology

A Study to Investigate Relative Bioavailability of Two Different Dosage Forms for Tozorakimab Via Subcutaneous Administration in Healthy Volunteers (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

Late Breaking Abstract - IL-33 signalling pathway biomarkers in severe viral lower respiratory tract disease: interim results from the prospective, observational UNIVERSAL study (ERS 2024) - "The ACCORD-2 trial indicated tozorakimab, an anti-IL-33 monoclonal antibody, may have clinical benefit for patients hospitalized with COVID-19...1B). Conclusion These results provide evidence of increased levels of IL-33 in vLRTD, beyond COVID-19, and a rationale to evaluate pathological roles for IL-33 in vLRTD."

Biomarker • Clinical • Late-breaking abstract • Observational data • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Otorhinolaryngology • Respiratory Diseases • Respiratory Syncytial Virus Infections • IL33

Late Breaking Abstract - FRONTIER-4: a phase 2a study to investigate tozorakimab (anti-IL-33 mAb) in COPD (ERS 2024) - P2 | "Tozorakimab was well tolerated. Conclusion Tozorakimab may improve lung function and reduce COPD exacerbations, especially in patients with frequent exacerbation history."

Late-breaking abstract • P2a data • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases • IL33

CDSCO Panel Approves AstraZeneca’s Protocol Amendment Proposal For COPD Drug Tozorakimab (Medical Dialogues) - "The Subject Expert Committee (SEC) under the Central Drug Standard Control Organisation (CDSCO) has approved AstraZeneca's proposal to amend the protocol titled 'Long-term Efficacy and Safety of Tozorakimab in Participants with Chronic Obstructive Pulmonary Disease with a History of Exacerbations'...This approval follows the presentation of protocol amendment version 3.0, dated 26.03.2024, protocol no. D9180C00008. This phase III, multicentre, randomised, double-blind, chronic-dosing, parallel-group, placebo-controlled extension study aims to evaluate the long-term efficacy and safety of Tozorakimab in COPD patients with a history of exacerbations (PROSPERO)."

Clinical protocol • Chronic Obstructive Pulmonary Disease

Population pharmacokinetic/target engagement modelling of tozorakimab in healthy volunteers and patients with chronic obstructive pulmonary disease. (PubMed, Br J Clin Pharmacol) - "The PK/TE model reliably quantified the relationship between PK and systemic TE of tozorakimab, with potential utility for predicting clinical dose-response relationships and supporting clinical dose selection."

Journal • PK/PD data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL33