itepekimab (SAR440340) / Sanofi, Regeneron - LARVOL DELTA

Bispecific Antibody Targeting IL-33 and TSLP for Treating Asthma and COPD (EAACI 2025) - "These antibodies demonstrated significantly enhanced activity compared to Tezepelumab in functional assays. Additionally, a series of anti-IL-33 antibodies were developed with superior potency relative to Itepekimab, as shown by IL-33 reporter assays and PBMC activation assays...Conclusion HXN-1013 is a bsAb designed to simultaneously block both TSLP and IL-33, with each arm exhibiting activity comparable to the parent antibodies. HXN-1013 has the potential to deliver more robust therapeutic effects, offering significant promise for improving clinical efficacy in the treatment of asthma and COPD."

Late-breaking abstract • Immunology • Inflammation • CRLF2 • IL13 • IL33 • IL5 • STAT5 • STAT5AWqe • TSLP

AERIFY-4: A Study to Investigate Long-term Safety and Tolerability of Itepekimab in Participants With COPD (clinicaltrials.gov) - P3 | N=700 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

Mechanisms and Treatment of Type 2 High and Low Asthma Endotypes. (PubMed, Clin Exp Allergy) - "Approved biologics for asthma management include using various interleukin antagonists and anti-immunoglobulin E, with Tezepelumab offering promising treatments for both type-2 high and type-2 low asthma patients. Novel therapeutic candidates, such as Itepekimab and depemokimab, have demonstrated promising results in a Phase 2 clinical trial in moderate-to-severe asthma patients."

Journal • Review • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Properties of the IL-33 blocker, itepekimab, enable greater efficacy in an airway inflammation mouse model. (ERS 2025) - No abstract available

Preclinical • Inflammation • Respiratory Diseases • IL33

Topical delivery of a human single-domain antibody targeting IL-33 to inhibit mucosal inflammation. (PubMed, Cell Mol Immunol) - "Compared with the anti-IL-33 control IgG itepekimab, the topical delivery of A12 resulted in significantly elevated corneal concentrations in vivo, which resulted in negligible ocular penetration...Furthermore, in another murine model of allergic asthma, inhaled A12 substantially reduced overall lung inflammation. Our findings revealed the capacity of UdAbs to penetrate mucosal barriers following noninvasive localized delivery, highlighting their potential as an innovative therapeutic strategy for modulating mucosal inflammation."

Journal • Asthma • Dry Eye Disease • Immunology • Inflammation • Mucositis • Ophthalmology • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL33

Press Release: Itepekimab met the primary endpoint in one of two COPD phase 3 studies (GlobeNewswire) - P3 | N=960 | AERIFY-1 (NCT04701983) | N=1,210 | AERIFY-2 (NCT04751487) | Sponsor: Sanofi | "The AERIFY-1 phase 3 study evaluating itepekimab in former smokers with inadequately controlled chronic obstructive pulmonary disease (COPD) met the primary endpoint of a statistically significant reduction in moderate or severe acute exacerbations compared to placebo of 27% at week 52, a clinically meaningful benefit. The AERIFY-2 phase 3 study did not meet the same primary endpoint, although a benefit was seen earlier in the trial...In the studies, patients were randomized to receive itepekimab every two weeks (AERIFY-1: n=375; AERIFY-2: n=326), every four weeks (AERIFY-1: n=377; AERIFY-2: n=303), or placebo (AERIFY-1: n=375; AERIFY-2: n=324), which was added to inhaled triple or double standard-of-care therapy. The primary endpoint analysis for AERIFY-1 and AERIFY-2 was the reduction in the annualized rate of acute moderate or severe COPD exacerbations with itepekimab treatment."

P3 data • Chronic Obstructive Pulmonary Disease

Bispecific Antibody Targeting Both IL33 and TSLP for Asthma and COPD (ATS 2025) - "In TSLPR/STAT5 reporter assays and BaF3 proliferation assays, these antibodies demonstrated a significant activity advantage compared to Tezepelumab. We produced a number of anti-IL33 antibodies with superior potency compared to Itepekimab based on IL33 reporter assays and PBMC activation assays... HXN-1013 simultaneously blocks TSLP and IL33, with each arm exhibiting activity comparable to the parent antibodies. HXN-1013 has great potential to enhance clinical efficacy for the treatment of asthma and COPD."

Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases • CRLF2 • IL13 • IL33 • IL5 • IL7R • STAT5 • STAT5AWqe • TSLP

From Mice to Humans: The IL-33 and IL-4Rα Blocking Antibodies, Itepekimab and Dupilumab, Modulate Distinct and Common Inflammatory Mediators in Asthma (ATS 2025) - "These findings highlight IL-33 and IL-4/IL-13 as key drivers of airway inflammation and remodeling, offering insights into the differential effects of targeting IL-4Rα or IL-33 pathways in asthma, either independently or in combination."

Preclinical • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL33 • IL4

Biologic Therapies for Severe Asthma: Current Insights and Future Directions. (PubMed, J Clin Med) - "The current biologics for severe asthma treatment include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP)...Depemokimab is an ultra-long-acting anti-IL-5 antibody with promising results in phase III trials as a twice-yearly biologic for T2-high asthma. Verekitug follows a similar dosing concept, targeting TSLP, but is still undergoing phase II trials. Itepekimab and astegolimab are two anti-IL-33 antibodies that could have a role in the future treatment of severe asthma. Tezepelumab is in a phase III clinical trial for CRSwNP. Besides new drugs, there is still a need for major research into biologics in severe asthma cases, namely with comparative studies, better biomarkers for predicting response, and the determination of optimal treatment duration."

Journal • Review • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Inflammation • Nasal Polyps • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis • IL13 • IL33 • IL4 • IL5

A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Non-cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=300 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Press Release: Sanofi: strong Q1 performance and 2025 guidance confirmed (Sanofi Press Release) - "itepekimab (IL33 mAb)...The CEREN 1 (clinical study identifier: NCT06834347) and CEREN 2 (clinical study identifier: NCT06834360) phase 3 studies of two dose regimens of itepekimab compared with placebo as add-on therapy to intranasal corticosteroids in patients with inadequately controlled CRSwNP commenced dosing the first patient. A proof-of-concept phase 2 study (clinical study identifier: NCT06691113) of two dose regimens of itepekimab compared with placebo in patients with inadequately controlled chronic rhinosinusitis without nasal polyps commenced dosing the first patient."

Trial status • Chronic Rhinosinusitis With Nasal Polyps

Itepekimab: expanding clinical studies beyond COPD into chronic rhinosinusitis (GlobeNewswire) - "Itepekimab is currently being explored in patients with COPD in two phase 3 studies AERIFY-1 (clinical study identifier: NCT04701983) and AERIFY-2 (clinical study identifier: NCT04751487) with the readout anticipated in H2 2025, and in one phase 2 study, AERIFY-3 (clinical study identifier: NCT05326412), with the readout anticipated in H2 2025....Finally, itepekimab is being explored in a phase 2 study (clinical study identifier: NCT06280391) in bronchiectasis, with the readout anticipated in 2026."

P2 data • P3 data • Bronchiectasis • Chronic Obstructive Pulmonary Disease

Sanofi launches Phase III clinical trial of subcutaneous IL-33 monoclonal antibody for chronic sinusitis in the country [Google translation] (Sina Corp) - "Itepekimab is the world's first subcutaneous IL-33 antibody drug to enter Phase III...This is the first time that the drug has started Phase III clinical trials for the treatment of chronic sinusitis, and it is also the first IL-33 antibody to enter Phase III for this indication...This is a randomized, double-blind, placebo-controlled, parallel-group, 52-week Phase III trial designed to evaluate the efficacy, safety, and tolerability of itepekimab in participants with poorly controlled chronic sinusitis with nasal polyps. The primary endpoint of the study was the change from baseline in endoscopic NPS and NCS at 24 weeks. A total of 102 institutions participated in the trial, with 33 participants planned to be enrolled in China and 210 participants planned to be enrolled internationally."

Trial status • Chronic Rhinosinusitis With Nasal Polyps

CEREN1: A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: Sanofi

New P3 trial • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

CEREN2: A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: Sanofi

New P3 trial • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Biologic Therapies for Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. (PubMed, COPD) - "Benralizumab (RR 0.89 [95% CI 0.78 to 1]), itepekimab (RR 0.81 [95% CI 0.61 to 1.07]) and tezepelumab (RR 0.83 [95% CI 0.61 to 1.12]) may reduce exacerbations as compared to placebo (all low certainty). Dupilumab probably reduced exacerbations more than mepolizumab (RR 0.74 [95% CI 0.62 to 0.89]) (moderate certainty)...Dupilumab is effective at improving patient-relevant outcomes in COPD with higher eosinophil levels. Other biological therapies, including tezepelumab, have no important effect on patient-relevant outcomes."

Clinical • Journal • Retrospective data • Review • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Targeting alarmins in asthma- From the bench to the clinic. (PubMed, J Allergy Clin Immunol) - "Tezepelumab, an anti-TSLP antibody has already been approved for the treatment of severe asthma. In this review we discuss our current understanding of alarmin biology with a primary focus on allergic airway diseases. We link the mechanistic corollaries to the clinical implications and advances in drug development targeting alarmins-focusing on currently approved treatments, those under study, as well as future potential targets in the alarmin signaling pathways."

Journal • Review • Allergy • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33 • IL5

Regeneron Provides Business Updates and Highlights from Broad Clinical Pipeline at the 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Results are expected from the Phase 3 AERIFY study in the second half of 2025, with a potential BLA submission to follow...Phase 2 study testing combinations of tirzepatide and mibavademab is ongoing, with initial data expected from both in the second half of 2025."

P2 data • P3 data • Chronic Obstructive Pulmonary Disease • Obesity

AERIFY-3: Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti--IL-33 mAb) in Participants With Chronic Rhinosinusitis Without Nasal Polyps (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

AERIFY-3: Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Sanofi | Trial completion date: Mar 2025 ➔ Aug 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

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

Role of Monoclonal Antibodies in the Management of Eosinophilic COPD: A Meta-analysis of Randomized Controlled Trials. (PubMed, Ann Am Thorac Soc) - "In patients with eosinophilic COPD receiving standard of care therapy, the use of monoclonal antibodies led to a significant reduction in annualized COPD exacerbation rate compared to placebo. Monoclonal antibodies have an acceptable tolerability and safety profile."

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

A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti--IL-33 mAb) in Participants With Chronic Rhinosinusitis Without Nasal Polyps (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Safety profile of drugs used in non-cystic fibrosis bronchiectasis: a narrative review. (PubMed, Ther Adv Drug Saf) - "Most of the drugs used in daily clinical practice for bronchiectasis are off-label with no randomised trials exploring their safety. This review aims at exploring the safety profile of drugs frequently used in clinical practice to manage bronchiectasis, including antibiotics (e.g. macrolides, aminoglycosides, polymyxins, fluoroquinolones, aztreonam), mucoactive therapy (e.g. hypertonic saline, mannitol, DNase and carbocisteine), anti-inflammatory therapy (inhaled corticosteroids) and drugs currently in development for use in bronchiectasis (e.g. brensocatib, benralizumab and itepekimab)."

Journal • Review • Bronchiectasis • Cough • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD. (PubMed, ERJ Open Res) - P3 | "Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses."

Journal • P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Tobacco Cessation • IL33