itepekimab (SAR440340) / Sanofi, Regeneron - LARVOL DELTA

CEREN-4: A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Adult Japanese Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P3 | N=20 | Not yet recruiting | Sponsor: Sanofi

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

CEREN-3: An Extension Study to Investigate the Long-term Safety and Tolerability of Itepekimab in Adult Participants With Inadequately Controlled Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P3 | N=380 | Enrolling by invitation | Sponsor: Sanofi | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Structures of clinical antibodies bound to IL-33 uncover two distinct epitopes underlying differential efficacy. (PubMed, MAbs) - "Here, we report the structures of three antibodies in clinical trial - etokimab, itepekimab, and tozorakimab - complexed with IL-33, determined by X-ray crystallography and cryo-electron microscopy. These structural and biochemical findings provide a molecular explanation for the differential efficacy of the three antibodies in inhibiting IL-33 signaling in cellular assays. Collectively, our results provide valuable insights into the molecular determinants of efficacy for existing IL-33 therapeutics and offer a structural framework for the rational design of next-generation IL-33 targeted inhibitors."

Journal • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL1RAP • IL33

Properties of the Il-33 Blocker, Itepekimab, Enable Greater Efficacy in an Airway Inflammation Mouse Model (ATS 2026) - No abstract available

Preclinical • Inflammation • Respiratory Diseases • IL33

CEREN-3: An Extension Study to Investigate the Long-term Safety and Tolerability of Itepekimab in Adult Participants With Inadequately Controlled Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P3 | N=380 | Not yet recruiting | Sponsor: Sanofi

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

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

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

Biologics in COPD: Current Status and Future Prospects. (PubMed, Tuberc Respir Dis (Seoul)) - "Subsequent Phase 3 trials have demonstrated substantial clinical benefits in defined patient subsets: dupilumab, which blocks interleukin (IL)-4 and IL-13 signaling, and mepolizumab, which targets IL-5, consistently reduced exacerbation frequency among patients with high blood eosinophil counts (≥300 cells/μL). In contrast, other biologics-benralizumab, tezepelumab, and IL-33/ST2 pathway inhibitors such as itepekimab, tozorakimab, and astegolimab-have shown variable efficacy, often dependent on biomarker profiles and patient characteristics. Together, these findings underscore the importance of precise patient stratification based on inflammatory endotypes. While biologics represent a major step forward for selected COPD populations, further research is required to clarify long-term outcomes, refine biomarker thresholds, and expand treatment options for non-eosinophilic COPD."

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

Comorbid Chronic Rhinosinusitis and Asthma: Shared Risk Factors and Treatment Implications-An EAACI Task Force Report. (PubMed, Allergy) - "It also evaluates current therapeutic strategies such as biologics, aspirin therapy after desensitization (ATAD), and endoscopic sinus surgery (ESS)...Dupilumab, mepolizumab, depemokimab, and omalizumab have emerged as transformative therapies, particularly for patients with severe type 2 inflammation...Itepekimab has shown its effect in asthma and is under investigation for CRSwNP...The report highlights gaps in the literature, such as the lack of head-to-head trials comparing biologics, ATAD, and surgery. Future research should focus on refining treatment algorithms, identifying biomarkers for treatment selection, and assessing long-term outcomes to optimize care for patients with CRS, asthma, and N-ERD."

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

COPD 2.0: Bronchodilators, biologics and beyond - A systematic review. (PubMed, Lung India) - "Biologic therapies therefore represent a new frontier in the personalized management of COPD, especially in eosinophilic phenotypes. Further high-quality studies are warranted to better define their long-term safety, cost-effectiveness, and broader applicability in COPD populations."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL4

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