itepekimab (SAR440340) / Sanofi, Regeneron - LARVOL DELTA

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

Pharmacokinetics of Subcutaneous Itepekimab Injection With an Autoinjector Device and Prefilled Syringe in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - "The exposure was similar for both devices in each body weight and injection site subgroup. Overall, systemic exposure of 300-mg single-dose itepekimab in healthy participants was comparable when administered subcutaneously via an AI device and PFS, with an acceptable safety profile in both device groups."

Journal • PK/PD data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL33

Reduction in exacerbations with itepekimab in former smokers with chronic obstructive pulmonary disease (COPD) by prior exacerbation frequency (ERS 2024) - P2 | "Itepekimab significantly increased time to ECOPD and reduced the frequency of ECOPD in former smokers, irrespective of exacerbation history. These findings will be confirmed by further studies. Figure."

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

The anti-IL-33 antibody, itepekimab, potently blocks airway inflammation post a single dose in mice (ERS 2024) - "Taken together, these results highlight that itepekimab is a potent blocker of IL-33 at doses as low as 1mg/kg, resulting in reduction of T1/T17 and T2 airway inflammation as well as lung remodeling in a chronic progressive lung inflammation mouse model."

Preclinical • Asthma • Chronic Obstructive Pulmonary Disease • Eosinophilia • Inflammation • Pneumonia • Respiratory Diseases • IL13 • IL1B • IL33 • IL4 • IL5 • TNFA

Latest Dupixent (dupilumab) and Itepekimab Data at ERS Highlight Scientific Innovation and Leadership in Respiratory Diseases (GlobeNewswire) - "These clinical and real-world abstracts presented in collaboration with Sanofi include four oral presentations and demonstrate the potential of targeting key drivers of type 2 inflammation and other pathways to address respiratory diseases, such as COPD and asthma, and improve patient outcomes...Among the notable Dupixent presentations at ERS is a pooled analysis of the previously reported Phase 3 BOREAS and NOTUS trials in uncontrolled COPD with evidence of type 2 inflammation...As shared in the abstract, the pooled analysis demonstrated that Dupixent patients (n=938) experienced a 31% reduction in the annualized rate of moderate or severe COPD exacerbations over 52 weeks compared to placebo (n=936; nominal p<0.0001)...Additionally, new research will be shared from the Phase 4 VESTIGE trial, a novel imaging study evaluating the effects of Dupixent on airway remodeling in certain adults with asthma."

P3 data • P4 data • Real-world • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases

Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate-to-severe atopic dermatitis: Results from two terminated phase II trials. (PubMed, Clin Transl Sci) - P2a, P2b | "Itepekimab was generally well tolerated, both alone and in combination with dupilumab. The lack of clinical efficacy for itepekimab observed in these studies suggests that IL-33 may not be a key pathogenic driver in moderate-to-severe AD."

Clinical • Journal • P2 data • PK/PD data • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Dermatitis • Dermatology • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33

AERIFY-2: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - P3 | N=1210 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • 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=960 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

Study design of a phase 2, randomized, double-blind, placebo-controlled trial of Itepekimab in patients with non-cystic fibrosis bronchiectasis (WBC 2024) - No abstract available

Clinical • P2 data • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Role of Monoclonal Antibodies in Patients With Eosinophilic Subtype COPD: A Meta-analysis of Randomized Controlled Trials (ATS 2024) - "Monoclonal antibodies ranged from Astegolimab, Benralizumab, Dupilumab, Itepekimab, and Mepolizumab. To conclude, in patients with eosinophilic subtype of COPD, the use of monoclonal antibodies led to a significant reduction in annualized exacerbation rate compared to standard of care. Monoclonal antibodies have an acceptable tolerability and safety profile."

Retrospective data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

The High Affinity Anti-IL-33 Antibody Itepekimab Potently Blocks IL-33 Induced Activation of the ST2/IL-1RAcP Signaling Complex and Inhibits Key Mediators of Airway Inflammation (ATS 2024) - "By its high affinity interaction with IL-33, itepekimab prevents IL-33 from forming an active signaling complex with ST2/IL-1RAcP and also inhibits IL-33 oxidation, thereby blocking IL-33-induced signaling in vitro. Intervention with itepekimab in a chronic HDM exposure model revealed that itepekimab potently inhibits lung inflammation and remodeling in vivo."

Inflammation • Pneumonia • Respiratory Diseases • IFNG • IL1RAP • IL33 • MYD88

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 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 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • 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 Non-cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Bronchiectasis • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Sanofi Gets CDSCO Panel Nod To Study COPD Drug Itepekimab (Medical Dialogues) - "The drug major Sanfi has got a go-ahead from the Subject expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct the clinical trial of the REGN3500 (Itepekimab) 300 mg (150 mg/mL) Solution in Chronic Obstructive Pulmonary Disease (COPD). This came after the drug maker Sanofi presented phase III clinical study protocol No..."

New trial • Chronic Obstructive Pulmonary Disease

AERIFY-3: Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Sanofi | Phase classification: P2a ➔ P2

Phase classification • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Regeneron Reports Fourth Quarter and Full Year 2023 Financial and Operating Results (GlobeNewswire) - "Select Upcoming 2024 Milestones: EC decision on regulatory submission for Dupixent for EoE in children (1–11 years of age) (second half 2024). sBLA acceptance for Dupixent in COPD with type 2 inflammatory phenotype (first quarter 2024) and FDA decision on sBLA (mid/second half 2024); EC decision on regulatory submission (second half 2024). Report results from ongoing Phase 3 study for Dupixent in chronic spontaneous urticaria (CSU) in biologic-naïve patients (fourth quarter 2024)....Complete enrollment of Phase 3 studies of itepekimab (IL-33 antibody) in COPD (second half 2024)."

Enrollment status • European regulatory • P3 data • sBLA • Chronic Obstructive Pulmonary Disease • Chronic Spontaneous Urticaria • Eosinophilic Esophagitis • Immunology

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

Enrollment open • 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=700 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

SAR445399 – an anti-IL-1R3 monoclonal antibody that blocks IL-1, IL-33 and IL-36 cytokine pathways for dermatologic diseases (ISDS 2023) - "Multiple therapies targeting individual members of the IL-1 family have only shown low to moderate efficacy in dermatologic disorders such as: αIL-36γ (Spesolimab) in AD, HS and PPP, αIL-33 (Itepekimab) in AD and IL-1R antagonist (Anakinra) or αIL-1R (MEDI-8968) in HS. Furthermore, an anti-murine surrogate of SAR445399 alleviates disease and inflammation in an Imiquimod-induced skin inflammation model with superior efficacy than IL-1 blockade alone. In summary, SAR445399 is a broad IL-1 pathway drug hitting 3 birds with 1 stone and is uniquely positioned to potentially raising the efficacy ceiling where a single agent therapy may not be fully efficacious in dermatology or other immunology areas."

Atopic Dermatitis • Dermatitis • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Psoriasis • IL1B • IL1RAP • IL33

Pharmacokinetic Study to Compare Itepekimab Exposure When Administered With an Autoinjector Versus Prefilled Syringe (clinicaltrials.gov) - P1 | N=90 | Completed | Sponsor: Sanofi

New P1 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases