Sanofi and Regeneron?s Dupixent approval in the EU as the first targeted medicine to treat young children with chronic spontaneous urticaria

Sanofi published the press releases attached hereto as Exhibits 99.1 and 99.2 which are incorporated herein by reference. Phase 2 studies of lunsekimig in two chronic respiratory diseases met their primary and key secondary endpoints compared to placebo. Lunsekimig, a novel bispecific Nanobody VHH, is made of five linked antibody fragments designed to simultaneously block TSLP and IL-13, two separate drivers of inflammation that contribute to tissue damage in asthma and related diseases.

In both studies, lunsekimig was well tolerated, with an acceptable safety profile. In the AIRCULES phase 2b study (clinical study identifier: NCT06102005), lunsekimig met its primary and key secondary endpoints demonstrating a statistically significant and clinically meaningful reduction in exacerbations and improvement in lung function, as measured by pre-bronchodilator forced expiratory volume in one second (pre-BD FEV). The study enrolled adult patients with moderate-to-severe asthma, a form of the disease marked by recurrent symptoms and frequent flareups despite standard-of-care treatment.

The DUET phase 2a proof-of-concept study (clinical study identifier: NCT06454240), of lunsekimig in chronic rhinosinusitis with nasal polyps (CRSwNP), met its primary endpoint of change in nasal polyp score from baseline and met its key secondary endpoints of change in patient reported nasal congestion/obstruction score and change in Lund-Mackay Computed Tomography (LMK-CT) score, all compared to placebo at Week 24. The separate exploratory VELVET phase 2b study (clinical study identifier: NCT06790121) evaluating lunsekimig in moderate-to-severe atopic dermatitis did not meet its primary endpoint of percent change from baseline in eczema area severity index (EASI) score. However, improvements were seen in the key secondary endpoints measuring skin clearance including EASI-75 (proportion of patients reaching a 75% or greater improvement in the EASI total score), and vIGA-AD 0/1 (proportion of patients reaching validated investigator global assessment scale for atopic dermatitis score of 0 or 1).

Across these studies, lunsekimig was generally well tolerated. In the AIRCULES study, among those who received at least one dose of lunsekimig, the most common (5%) treatment-emergent adverse events (TEAEs) were nasopharyngitis, upper respiratory tract infection, headache, and dose scheduling errors. In the DUET study, among those who received at least one dose of lunsekimig, the most common (5%) TEAEs were injection site reaction or erythema, viral upper respiratory tract infection, nasopharyngitis, epistaxis, ear pain, and increased creatine phosphokinase.

Overall, rates of serious adverse events and TEAEs leading to treatment discontinuation in both studies were similar in the lunsekimig group and the placebo group. In the VELVET study, lunsekimig was generally well tolerated and had a safety profile consistent with the other studies. Detailed results from the AIRCULES, DUET, and VELVET studies will be presented at upcoming medical congresses.

Lunsekimig is currently in clinical development in the AIRLYMPUS phase 2 study in high-risk asthma (clinical study identifier: NCT06676319) and in the PERSEPHONE and the THESEUS phase 3 studies (clinical study identifiers PERSEPHONE: NCT07190209, THESEUS: NCT07190222), and its safety and efficacy have not been evaluated by any regulatory authority. The AIRCULES study was a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase 2b study to evaluate the efficacy, safety, and tolerability of subcutaneous lunsekimig added to standard of care in adult patients with moderate-to-severe asthma across the range of FeNO (fractional exhaled nitric oxide) and eosinophil values. Lunsekimig was administered in multiple dosing regimens, and the primary endpoint was the annualized rate of asthma exacerbation events over 48 weeks.

The key secondary endpoint evaluated lung function improvement, as measured by pre-BD FEV at Week 48. Lung function was assessed indirectly by measuring the volume of air a patient can exhale forcefully in one second. The study included sites across the US, Canada, Argentina, Brazil, Chile, China, India, Israel, Japan, Mexico, South Africa, South Korea, Turkey, and the UK.

The DUET study was a randomized, double-blind, placebo-controlled, parallel-group phase 2a study designed to evaluate the efficacy, safety, and tolerability of subcutaneous lunsekimig in adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Key objectives include measuring the efficacy and safety of lunsekimig compared to placebo over 24 weeks. The primary endpoint was change in nasal polyps score from baseline at Week 24 through bilateral endoscopy and the key secondary endpoints were change from baseline in patient-reported nasal congestion/obstruction score and change from baseline in LMK-CT score, both at Week 24.

The study included sites across the US, Argentina, Belgium, Bulgaria, Poland, and the UK. The VELVET study was a randomized, double-blind, placebo-controlled, multicenter exploratory study to assess the efficacy and safety of three subcutaneous dose regimens of lunsekimig in adult patients with moderate-to-severe atopic dermatitis. Key objectives include measuring the efficacy and safety of subcutaneous lunsekimig compared to placebo over 24 weeks.

Lunsekimig was administered in three dosing regimens, and the primary endpoint was the percent change in EASI score from baseline at week 24. The study included sites across the United States, Czechia, Japan, and Poland. The European Commission has approved Dupixent (dupilumab) for the treatment of moderate-to-severe chronic spontaneous urticaria (CSU) in children aged two to 11 years with inadequate response to histamine-1 antihistamines (H1AH) and who are naive to anti-immunoglobulin E (IgE) therapy for CSU.

This expands the previous approval in the EU for adults and adolescents aged 12 years and older with CSU, a chronic, inflammatory skin disease that causes sudden and debilitating hives and recurring itch. The approval in the EU is based on data from the LIBERTY-CUPID clinical study program. This includes an extrapolation of efficacy data in adults from two phase 3 studies (Study A and Study C; clinical study identifier: NCT04180488) complemented by pharmacokinetic, safety, and efficacy data from the single-arm CUPIDKids phase 3 study in children aged two to 11 years with CSU (clinical study identifier: NCT05526521).

Study A and Study C demonstrated Dupixent significantly reduced urticaria activity (a composite of itch and hives) and individual measures of itch and hive severity compared with placebo at Week 24.