tozorakimab (MEDI3506) / AstraZeneca - LARVOL DELTA

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

MIRANDA: Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations (clinicaltrials.gov) - P3 | N=1240 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2026 ➔ Aug 2026 | Trial primary completion date: Sep 2026 ➔ Jun 2026

Trial completion date • Trial primary completion date • 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=1060 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Aug 2025 ➔ May 2026 | Trial primary completion date: Jun 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • 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=1060 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Aug 2025 ➔ May 2026 | Trial primary completion date: Jun 2025 ➔ Feb 2026

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

Long-term Efficacy and Safety of Tozorakimab in Participants With Chronic Obstructive Pulmonary Disease With a History of Exacerbations (PROSPERO). (clinicaltrials.gov) - P3 | N=1596 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Jun 2026

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

A Phase 2b Diabetic Kidney Disease Study (clinicaltrials.gov) - P2 | N=609 | Completed | Sponsor: AstraZeneca | Phase classification: P2b ➔ P2

Phase classification • Diabetic Nephropathy • Nephrology • Renal Disease

Inhibition of Interleukin-33 to Reduce Glomerular Endothelial Inflammation in Diabetic Kidney Disease. (PubMed, Kidney Int Rep) - P2b | "Therefore, FRONTIER-1 was designed to test the safety and efficacy of the IL-33-targeted monoclonal antibody tozorakimab in patients with DKD...Treatment with dapagliflozin for 6 weeks did not alter these biomarkers significantly. We show that blocking the IL-33 pathway may mitigate glomerular endothelial inflammation in DKD. The findings from the FRONTIER-1 study will provide valuable insights into the therapeutic potential of IL-33 inhibition in DKD."

Journal • Diabetes • Diabetic Nephropathy • Inflammation • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Type 2 Diabetes Mellitus • CCL2 • IL33 • TNFA • TNFRSF1A

Long-term Efficacy and Safety of Tozorakimab in Participants With Chronic Obstructive Pulmonary Disease With a History of Exacerbations (PROSPERO). (clinicaltrials.gov) - P3 | N=1596 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2025 ➔ Feb 2026 | Trial primary completion date: Jul 2025 ➔ Feb 2026

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

IL-33 Inhibition with Tozorakimab for Diabetic Kidney Disease: A Randomized, Placebo-Controlled Phase 2b Study (ERA-EDTA 2024) - P2b | "All participants received 10 mg of dapagliflozin Days 85–168, discontinuing existing SGLT2i if applicable. This study did not demonstrate a clinically meaningful reduction in UACR with tozorakimab treatment in patients with T2D and CKD. Further investigation is warranted to clarify the role of IL-33 in DKD."

Clinical • P2b data • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Infectious Disease • Inflammation • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Renal Disease • Type 2 Diabetes Mellitus • IL33

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

Enrollment closed

Distinct Pharmacological Profiles of IL-33 Antibodies (ATS 2024) - "From the range of IL-33 antibodies tested, the ability to inhibit IL-33ox biological effects was unique to tozorakimab and appeared to be dependent on epitope, which is distinct for tozorakimab versus other IL-33 antibodies. Tozorakimab is under clinical investigation to reduce excess inflammation and epithelial remodelling in IL-33-driven disease."

Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IFNG • IL33

Towards precision medicine in COPD: Targeting type 2 cytokines and alarmins. (PubMed, Eur J Intern Med) - "Two phase III randomized clinical trials (RCTs) showed a modest reduction in exacerbations in COPD patients with eosinophilic phenotype treated with mepolizumab (anti-IL-5) or benralizumab (anti-IL-5Rα). A phase III RCT showed a 30% reduction in exacerbations in COPD patients with ≥ 300 eosinophils/μL treated with dupilumab (anti-IL-4Rα)...Several ongoing RCTs are evaluating the efficacy and safety of anti-TSLP (tezepelumab), anti-IL-33 (itepekimab, tozorakimab), and anti-ST2 (astegolimab) in patients with COPD, who experience exacerbations. In conclusion, targeting T2 inflammation or epithelial-derived alarmins might represent a step forward in precision medicine for the treatment of a subset of COPD."

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

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

Enrollment open

Advancements in Diabetic Kidney Disease Management: Integrating Innovative Therapies and Targeted Drug Development. (PubMed, Am J Physiol Endocrinol Metab) - "Emerging agents including GLP-1 agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, Lixudebart, and tozorakimab, mesenchymal stem/stromal cell infusion, and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Hypertension • Immunology • Inflammation • Metabolic Disorders • Nephrology • Oncology • Renal Disease

CDSCO Panel Approves AstraZeneca's Protocol Amendment Proposal For COPD Drug Study (Medical Dialogues) - "The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has approved the protocol amendment proposal presented by the drug major AstraZeneca for the drug MEDI3506 (Tozorakimab), an anti-IL-33 antibody. As the recent SEC meeting for Pulmonary meeting held on 5th March 2024, the expert panel reviewed the proposal for protocol amendment No. 2.0 (version 3.0) dated 23 Jun 2023, protocol No. D9180C00003."

Clinical protocol • Chronic Obstructive Pulmonary Disease

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants. (PubMed, Clin Pharmacol Drug Dev) - P1 | "There were no clinically relevant trends over time in clinical laboratory (hematology, clinical chemistry, and urinalysis), electrocardiogram, or vital sign parameters in any treatment group. Overall, tozorakimab demonstrated dose-dependent systemic exposure in healthy Chinese participants and was well tolerated, with no safety concerns identified in this study."

Clinical • Journal • P1 data • PK/PD data • Hematological Disorders

Long-term Efficacy and Safety of Tozorakimab in Participants With Chronic Obstructive Pulmonary Disease With a History of Exacerbations (PROSPERO). (clinicaltrials.gov) - P3 | N=1596 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2026 ➔ Jul 2025

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

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

New P1 trial

Tozorakimab: Data from P3 PROSPERO trial (NCT05742802) for COPD post 2025 (AstraZeneca) - Q4 & FY2023 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

Tozorakimab: Data from P3 OBERON trial (NCT05166889) for COPD post 2025 (AstraZeneca) - Q4 & FY2023 Results: Data from P3 TITANIA trial (NCT05158387) for COPD post 2025

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

A randomized phase 1 study of the anti-interleukin-33 antibody tozorakimab in healthy adults and patients with chronic obstructive pulmonary disease. (PubMed, Clin Pharmacol Ther) - P1 | "Additionally, biomarker studies demonstrated proof of mechanism. Overall, these data support the further clinical development of tozorakimab in COPD and other inflammatory diseases."

Clinical • Journal • P1 data • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL33 • IL5