itepekimab (SAR440340) / Sanofi, Regeneron - LARVOL DELTA

Updates in COPD Management: From Inflammatory Pathways to Targeted Therapies. (PubMed, Eur J Clin Invest) - "COPD management is evolving toward precision medicine, guided by inflammatory phenotypes, biomarkers, and individualised risk profiles. Continued investigation into targeted biologics, anti-inflammatory agents, and incorporating biomarkers into clinical practice may improve outcomes and reduce disease burden."

Biomarker • Journal • Review • Cardiovascular • Chronic Obstructive Pulmonary Disease • Cognitive Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33

Tozorakimab restores epithelial dysfunction in COPD (ERS 2026) - "Tozorakimab is a human therapeutic mAb with a dual pharmacological profile that can inhibit both IL-33 activities with demonstrated ability to reverse epithelial dysfunction in COPD. Tozorakimab is under clinical investigation in COPD. Table."

Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases • EGFR • IL33 • IL5 • MUC5AC

Efficacy of Biologics in Patients with Moderate to Very Severe COPD: A Systematic Review. (PubMed, Int J Chron Obstruct Pulmon Dis) - "Sixteen publications were included, covering 12 studies of seven biologics (astegolimab, benralizumab, dupilumab, itepekimab, mepolizumab, tezepelumab and tozorakimab). Improvements in SGRQ total score were observed in patients with BEC ≥300 cells/µL (dupilumab and tezepelumab) and astegolimab improved SGRQ-C total score in patients with BEC >170 cells/µL. Overall, AECOPD reductions and improvements in lung function and health-related quality of life in patients with moderate to very severe COPD varied by biologic and baseline BEC subgroup; within studies, efficacy was generally greater in patients with an elevated baseline BEC, suggesting these patients may benefit most from biologic treatment."

Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

AERIFY-4: A Study to Investigate Long-term Safety and Tolerability of Itepekimab in Participants With COPD (clinicaltrials.gov) - P3 | N=669 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

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

Late Breaking Abstract - PRT-089Q01, an IND-enabling anti-interleukin-33 antibody, represents a potential best-in-class agent for chronic obstructive pulmonary disease (ERS 2026) - "Notably, Tozorakimab and Itepekimab recognize distinct epitopes on IL-33red. With its unique molecular format, potency and favorable developability, PRT-089Q01 holds great potential to become a best-in-class antibody targeting IL-33."

Late-breaking abstract • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CXCL8 • IFNG • IL33 • IL6

Effects of itepekimab on airway inflammation and structure in former and current smokers with COPD: a phase 2a mechanistic study (ERS 2026) - "This study underscores the molecular and cellular heterogeneity of COPD. Itepekimab induced transcriptomic changes in both FS and CS. Itepekimab reduced type 2 and non–type-2 inflammation and increased epithelial barrier repair in FS within 12 weeks of treatment."

P2a data • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases • CCL11 • CXCL8 • IL33 • IRAK4

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=66 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • 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=59 | Active, not recruiting | Sponsor: Sanofi | Enrolling by invitation ➔ Active, not recruiting | N=380 ➔ 59 | Trial completion date: Dec 2028 ➔ Feb 2027 | Trial primary completion date: Dec 2028 ➔ Feb 2027

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

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=0 | Withdrawn | Sponsor: Sanofi | N=20 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Molecular mechanisms of allergic type 2 immunity in the pathogenesis of Crohn's disease: From epithelial alarmins to IgE signaling. (PubMed, Cell Mol Biol (Noisy-le-grand)) - "Understanding these allergic mechanisms opens novel therapeutic avenues, including anti-IgE (omalizumab), anti-IL-4/IL-13 (dupilumab), anti-IL-33 (itepekimab), anti-TSLP (tezepelumab), and mast cell stabilizers (ketotifen). This review integrates current molecular evidence on allergic reactions in CD and highlights their clinical and therapeutic relevance. Recognizing type 2 immune signatures in subsets of CD patients may enable more personalized treatment strategies."

Journal • Review • Allergy • Crohn's disease • Eosinophilia • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL13 • IL33 • IL4 • IL5 • IL6 • TNFA

Sanofi drops two more programmes in R&D clear-out (pharmaphorum) - "Regeneron-partnered itepekimab was in two phase 3 trials in chronic obstructive pulmonary disease (COPD), AERIFY 1 and 2...While the drug achieved its primary objective in AERIFY 1, achieving a statistically significant reduction in moderate or severe COPD exacerbations, that was not replicated in AERIFY 2...Oral, small-molecule TNF inhibitor balinatunfib...was in a pair of phase 2 trials in Crohn's disease and ulcerative colitis...the company has now revealed that interim results from the studies did not meet the internal efficacy expectations on clinical endpoints and/or the primary endpoint of clinical remission."

Discontinued • Chronic Obstructive Pulmonary Disease • Crohn's disease • Immunology • Ulcerative Colitis

AERIFY-4: A Study to Investigate Long-term Safety and Tolerability of Itepekimab in Participants With COPD (clinicaltrials.gov) - P3 | N=0 | Sponsor: Sanofi | N=22 ➔ 0

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

Efficacy and safety of Itepekimab in patients with non-cystic fibrosis bronchiectasis (WBC 2026) - No abstract available

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

Efficacy and Safety of Itepekimab in Patients with Non-Cystic Fibrosis Bronchiectasis (WBC 2026) - No abstract available

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

Efficacy and Safety of Itepekimab in Patients with Non-Cystic Fibrosis Bronchiectasis (WBC 2026) - No abstract available

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

Airway epithelial dysfunction in asthma pathogenesis: epigenetic mechanisms, inflammatory crosstalk, and therapeutic opportunities. (PubMed, Front Allergy) - "Finally, we discuss translational opportunities, including HDAC inhibitors, miRNA-based therapies, and the potential of anti-alarmin biologics (tezepelumab, itepekimab) and downstream cytokine receptor antagonists (dupilumab) to partially restore epithelial function and progenitor states. We acknowledge that, given current data availability, this review is weighted toward T2-high (eosinophilic) endotypes; mechanistic characterization of T2-low asthma remains an important area for future investigation. This framework reconceptualizes asthma not only as a disorder of dysregulated immunity, but as a disease of maladaptively reprogrammed barrier tissue, with important implications for disease prevention, endotype-specific treatment, and the goal of achieving true biological remission."

Journal • Review • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CDH1 • CLDN18 • IL13 • IL33 • TSLP

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=216 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

Epithelial alarmins TSLP, IL-33, and IL-25 in asthma pathogenesis: mechanistic roles and therapeutic implications. (PubMed, Mol Biol Rep) - "Epithelial alarmins represent critical upstream drivers of asthma pathogenesis, orchestrating diverse inflammatory pathways that determine disease endotypes and severity. Therapeutic targeting of TSLP, IL-33, and IL-25 offers a paradigm shift from downstream cytokine inhibition to source-directed intervention, with potential to reduce exacerbations, prevent airway remodelling, and improve disease control across different asthma phenotypes. The success of anti-TSLP therapy and ongoing clinical development of IL-33 and IL-25 inhibitors validate epithelial alarmins as essential molecular targets for precision medicine approaches in severe and refractory asthma."

Journal • Review • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CRLF2 • IL17A • IL17RA • IL17RB • IL1RAP • IL33 • TSLP

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=231 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

LTS18420: An extension study to investigate the long-term safety and tolerability of itepekimab in adult participants with inadequately controlled chronic rhinosinusitis with nasal polyps (clinicaltrialsregister.eu) - P2/3 | N=69 | Not yet recruiting | Sponsor: Sanofi-Aventis Recherche & Developpement

New P2/3 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 Chronic Rhinosinusitis Without Nasal Polyps (clinicaltrials.gov) - P2 | N=66 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Feb 2027 ➔ Aug 2026 | Trial primary completion date: Aug 2026 ➔ Mar 2026

Trial completion date • Trial primary completion date • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Itepekimab for chronic obstructive pulmonary disease therapy. (PubMed, Expert Opin Biol Ther) - "This review summarizes the scientific rationale for the potential use of itepekimab in COPD and reviews the available clinical data. Based on existing clinical data, itepekimab may be a potential therapy for COPD that can be easily administered at home, with dosing tailored to the disease phase (every 2 weeks during exacerbation and every 4 weeks during stable state)."

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

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