itepekimab (SAR440340) / Sanofi, Regeneron - LARVOL DELTA

Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast. (PubMed, Pulm Ther) - "In the phase 3, 52-week ASPEN trial, brensocatib significantly reduced exacerbation burden, and the 25-mg dose reduced lung function decline and nominally significantly improved patient-reported symptoms compared with placebo. Additional therapies in development include other DPP1 inhibitors (verducatib and HSK31858) and drugs targeting phosphodiesterase 3/4 inhibition (ensifentrine) and anti-interleukin-33 (itepekimab). Overall, the future is promising for patients with the historically neglected and underdiagnosed disease bronchiectasis, with growing awareness and new therapeutic tools becoming available. Podcast (MP4 81554 KB)."

Journal • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pediatrics • Pulmonary Disease • Respiratory Diseases • IL33

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 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

Novel Maintenance Therapies for Chronic Obstructive Pulmonary Disorder. (PubMed, Ann Pharmacother) - "Evidence supports LABA/LAMA with nuanced use of ICS. Several novel therapies are approved or are being studied for patients suboptimally controlled. Pharmacists can assist in medication optimization and access; however, patient-specific factors like exacerbation history, blood eosinophils, and COPD endotype must be considered. Implementing early identification screening tools such as CAPTURE should factor into patient assessment."

Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Pneumococcal Infections • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

The IL-33 and IL-4Rα blocking antibodies itepekimab and dupilumab modulate both distinct and common inflammatory mediators in asthma. (PubMed, Sci Transl Med) - "As observed in mice, combination treatment in individuals with allergic asthma did not provide additional benefit compared to monotherapy. Overall, these results provide insight into the differences in targeting IL-4Rα or IL-33 pathways in asthma independently or in combination."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL33 • IL4R

Study design of a phase 2, randomized, double-blind, placebo-controlled trial of Itepekimab in patients with non-cystic fibrosis bronchiectasis (WBC 2024) - P2 | "Results from this Phase 2 trial will provide information about efficacy, safety, and dosing for itepekimab in the treatment of NCFB. ClinicalTrials.gov Identifiers: NCT06280391."

Clinical • P2 data • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pneumonia • Pulmonary Disease • Respiratory Diseases • CD4 • IL33

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=312 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Aug 2026 ➔ Feb 2026 | Trial primary completion date: Mar 2026 ➔ Sep 2025

Trial completion date • Trial primary completion date • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

AERIFY-2: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P3 | N=1239 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

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

AERIFY-1: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P3 | N=1127 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

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

Late Breaking Abstract - Bispecific antibody targeting IL33 and TSLP for treating asthma and COPD (ERS 2025) - " Multiple high-potency anti-TSLP antibodies were generated targeting Site I (TSLPR), Site II (IL7Rα), and biparatopic antibodies that target both sites, displaying significantly better activity than Tezepelumab in TSLP reporter assay and CCL17 release from PBMCs. A series of anti-IL33 antibodies were developed and optimized using AI algorithms, with superior potency to Itepekimab in IL33 reporter and PBMC activation assays... HXN-1013 is a bsAb designed to simultaneously block both TSLP and IL33. 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 • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pneumonia • Respiratory Diseases • CRLF2 • IL33 • IL7R • TSLP

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

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

Patient experiences during COPD care using biologics: a scoping review (ERS 2025) - "Evidence of harm (cancer and pneumonia) was observed in patients treated with infliximab...Safety outcomes found moderate certainty for dupilumab, mepolizumab and benralizumab... Careful patient selection and identification of COPD phenotypes and endotypes are crucial to benefit from Bs."

Clinical • Review • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases

IL-33 expands lung plasma cells and increases autoantibody production (ERS 2025) - "Importantly, therapeutic blockade with itepekimab, an anti-IL-33 antibody, significantly reduced autoantibody production during HDM exposure in humanized mice, indicating that this process is dependent on IL-33 signaling...Collectively, our findings reveal that IL-33 disrupts the B cell compartment in the lung and facilitates autoantibody production, which may contribute to the pathogenesis of asthma and COPD. These insights reveal an additional mechanism by which targeting IL-33 can modulate the pathophysiology of lung diseases."

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

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

Therapeutic application of cytokine antagonists in chronic obstructive pulmonary disease (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "Biologics targeting type 2 inflammation, such as Tezepelumab (targeting thymic stromal lymphopoietin, TSLP), Itepekimab and Astegolimab (targeting IL-33), and Dupilumab (targeting IL-4/IL-13), have demonstrated potential in clinical trials to improve outcomes and enhance the quality of life for COPD patients. This article systematically outlines the molecular mechanisms of type 2 inflammation in COPD and the progress in targeted therapies. It emphasizes that the clinical translation of biologics must be guided by precision medicine, integrating mechanistic research with real-world evidence to advance COPD treatment towards "individualized intervention." Future research needs to further elucidate the interactions between type 2 and non-type 2 inflammatory phenotypes and to explore combination therapeutic strategies, in order to provide more comprehensive solutions for the prevention and management of COPD."

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

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

Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications. (PubMed, Pharmaceuticals (Basel)) - "Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma."

Biomarker • Journal • Review • Asthma • Eosinophilia • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL17A • IL33 • IL4 • IL5

AERIFY-3: Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD (clinicaltrials.gov) - P2 | N=49 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

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

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

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