amlitelimab SC (KY1005 SC) / Sanofi - LARVOL DELTA

O13 Impact of amlitelimab (an anti-OX40 ligand antibody) on atopic dermatitis by body region: post hoc results from the STREAM-AD phase IIb study of moderate-to-severe atopic dermatitis. (PubMed, Br J Dermatol) - P2 | "In part 1, adult participants with moderate-to-severe AD were randomized (1 : 1 : 1 : 1 : 1) to subcutaneous amlitelimab (250 mg with 500 mg loading dose, n = 77; 250 mg, n = 78; 125 mg, n = 77; 62.5 mg, n = 79) or placebo (n = 79) every 4 weeks. The data suggest that amlitelimab may address the heterogeneous clinical presentation of moderate-to-severe AD, especially for hard-to-treat body regions such as the head and neck area and lesions.TableLeast-squares mean percentage change from baseline (%ΔBL) in Eczema Area and Severity Index subscores by body regionLeast-squares mean %ΔBL (SE)Amlitelimab (Q4W)Placebo (Q4W)250 mg + LD250 mg125 mg62.5 mgNumber7778777979Head and neck Erythema-62.1 (6.04)-55.1 (6.23)-54.2 (5.82)-47.1 (6.01)-24.5 (6.45) Oedema/papulation-65.6 (6.35)-60.4 (6.64)-62.0 (6.18)-50.0 (6.39)-29.8 (6.77) Excoriation-75.3 (6.91)-70.5 (6.90)-66.8 (6.76)-59.5 (6.89)-29.3 (7.43) Lichenification-72.0..."

Clinical • Journal • P2b data • Retrospective data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • TNFSF4

A Post Hoc Analysis of Atopic Dermatitis of the Head and Neck and Other Body Regions from the Amlitelimab STREAM-AD Phase 2b Study. (PubMed, Dermatol Ther (Heidelb)) - P2 | "Improvements in AD signs and severity were observed with amlitelimab across all body regions. Notably, clinical responses were sustained following treatment withdrawal, supporting the potential for extended dosing intervals and durable off-treatment efficacy. Amlitelimab may be a treatment option for hard-to-treat head and neck AD that disproportionately impairs quality of life."

Journal • P2b data • Retrospective data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

A Bioequivalence Study of Amlitelimab Delivered by 2 Different Devices in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=212 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed

SHORE: A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis on Background Topical Corticosteroids (clinicaltrials.gov) - P3 | N=643 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Amlitelimab Reduces Th2-, Th1-, and Th17/22-Related Gene Expression and Protein Levels in Adults with Moderate-to-Severe Atopic Dermatitis: Results from STREAM-AD Phase 2b Analysis (ISDS 2025) - P2 | "In Part 1, adults with moderate-to-severe AD were randomized to receive subcutaneous amlitelimab (250mg + 500mg loading dose, 250mg, 125mg, or 62.5mg) or placebo every 4W. Additionally, it reduced protein levels associated with Th17/22-related inflammation including the proinflammatory cytokine IL-32 (p<0.001). Amlitelimab effectively normalized/reduced AD-associated gene and protein expression, reinforcing OX40L blockade as a relevant therapeutic strategy for AD-related inflammation."

Clinical • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • CXCL10 • CXCL9 • IL32 • TNFSF4

COAST 1: A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis (clinicaltrials.gov) - P3 | N=601 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Proof-of-concept Study Evaluating Subcutaneous Amlitelimab in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov) - P2 | N=90 | Terminated | Sponsor: Sanofi | Trial completion date: Jan 2027 ➔ Oct 2025 | Active, not recruiting ➔ Terminated; Sponsor decision; the decision is not related to any safety concern

Trial completion date • Trial termination • Dermatology • Hidradenitis Suppurativa • Immunology

Amlitelimab SC: “All primary and key secondary endpoints met in AD phase 3 study”; Atopic dermatitis (Sanofi) - Q3 2025 Results

P3 data • Atopic Dermatitis • Immunology

Amlitelimab SC: “Encouraging efficacy, specifically in difficult-to-treat subgroup in phase 2 study”; Asthma (Sanofi) - Q3 2025 Results

P2 data • Asthma • Immunology

ESTUARY: A Study to Evaluate the Treatment Response and Safety of Two Dose Regimens of Subcutaneous Amlitelimab Compared With Treatment Withdrawal in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis (clinicaltrials.gov) - P3 | N=1500 | Recruiting | Sponsor: Sanofi | Trial primary completion date: Oct 2026 ➔ Jun 2026

Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

ESTUARY: A Study to Evaluate the Treatment Response and Safety of Two Dose Regimens of Subcutaneous Amlitelimab Compared With Treatment Withdrawal in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis (clinicaltrials.gov) - P3 | N=1500 | Recruiting | Sponsor: Sanofi | N=961 ➔ 1500 | Trial primary completion date: Jun 2026 ➔ Oct 2026

Enrollment change • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Population Pharmacokinetic and Pharmacodynamic Modeling for the Prediction of the Extended Amlitelimab Phase 3 Dosing Regimen in Atopic Dermatitis. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The PopPK model was developed using phase 1 (healthy volunteers) and phase 2 (participants with AD) trial data, including individual exposure variables from the STREAM-AD phase 2b trial following subcutaneous amlitelimab doses ranging from 62.5 to 250 mg given every 4 weeks (Q4W). Simulations identified that a twofold dose reduction would allow participants < 40 kg to achieve amlitelimab exposures within the range observed in participants ≥ 40 kg on 250 mg Q4W or Q12W. These results support evaluation of a Q12W dosing regimen for adults and adolescents in phase 3 trials."

Journal • P3 data • PK/PD data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

A Bioequivalence Study of Amlitelimab Delivered by 2 Different Devices in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=212 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open

Durable maintenance of EASI-90 with amlitelimab in adults with moderate-to-severe atopic dermatitis: 52-week results from the STREAM-AD phase 2b trial (EADV 2025) - P2 | "Adults with moderate-to-severe AD (N=390) were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab every 4 weeks (Q4W; 250 mg + 500-mg loading dose [LD], n=77; 250 mg, n=78; 125 mg, n=77; or 62.5 mg, n=79) or placebo Q4W (n=79) in Part 1. The results demonstrate that a high proportion of clinical responders achieved EASI-90 response at Week 24. The majority maintained EASI-90 response with continued amlitelimab treatment at Week 52. Notably, EASI-90 was also maintained at Week 52 after 28 weeks of withdrawal from amlitelimab by the majority of Week 24 EASI-90 responders."

Clinical • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus • TNFSF4

ATLANTIS: Open Label, Long-term Study Evaluating Safety and Efficacy of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=901 | Recruiting | Sponsor: Sanofi | Trial completion date: Oct 2028 ➔ Jun 2031 | Trial primary completion date: Oct 2028 ➔ Jun 2031

Trial completion date • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Late Breaking Abstract - Amlitelimab phase 2 clinical trial results in patients with moderate-to-severe asthma (ERS 2025) - P2 | "Adults (N=437; 18-75yrs) with moderate-to-severe asthma were randomized 2:2:1:2 to subcutaneous amlitelimab 250mg +500mg loading dose (LD), 125mg +250mg LD, 62.5mg +125mg LD, or placebo (PBO) given every 4wks (Q4W) for 24wks, then Q12W to Wk60. Amlitelimab was well tolerated, reduced AAER and improved FEV1 and asthma control in patients with moderate-to-severe asthma, notably in subgroups with elevated EOS or NEUT. Efficacy enrichment by NEUT suggests amlitelimab may modulate inflammation beyond Type 2."

Clinical • IO biomarker • Late-breaking abstract • P2 data • Asthma • Immunology • Inflammation • Respiratory Diseases

Press Release: Sanofi’s amlitelimab met all primary and key secondary endpoints in the COAST 1 phase 3 study in adults and adolescents with atopic dermatitis (Sanofi Press Release) - "Positive results from the global COAST 1 phase 3 study (clinical study identifier: NCT06130566) showed that amlitelimab, a fully human non-T cell depleting monoclonal antibody that targets OX40-ligand (OX40L), dosed either every four weeks (Q4W) or every 12 weeks (Q12W), met all primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful skin clearance and disease severity compared to placebo at Week 24 in patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD). Amlitelimab was well-tolerated, with no new safety concerns identified in this study."

P3 data • Atopic Dermatitis

The OCEANA clinical development program of amlitelimab in AD, which includes COAST 1 and four other phase 3 studies (SHORE, COAST 2, AQUA, and ESTUARY) is anticipated to read out through 2026 and comprises the foundation for potential global regulatory submissions. (Sanofi Press Release)

Clinical data • Atopic Dermatitis

A Bioequivalence Study of Amlitelimab Delivered by 2 Different Devices in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=212 | Not yet recruiting | Sponsor: Sanofi

New P1 trial

Improvement and maintenance of clinical outcome assessments in atopic dermatitis with amlitelimab. (PubMed, J Eur Acad Dermatol Venereol) - P2 | "Amlitelimab treatment led to clinically meaningful improvements in COAs by Week 24 versus placebo. COA improvements were maintained at Week 52 in patients continuing amlitelimab, as well as in patients who withdrew from amlitelimab, supporting the durable response of amlitelimab and the viability of extended drug dosing, which may ease treatment burden."

Clinical data • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

AQUA: A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab on Background Topical Corticosteroids Therapy in Participants Aged 12 Years and Older With Moderate-to-severe AD Who Have Had an Inadequate Response to Prior Biologic Therapy or an Oral JAK Inhibitor (clinicaltrials.gov) - P3 | N=330 | Recruiting | Sponsor: Sanofi | N=249 ➔ 330

Enrollment change • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Amlitelimab SC: First data from P3 COAST-1 and COAST-2 trials (NCT06130566, NCT06181435) for atopic dermatitis in H2 2025 (Sanofi) - Q2 2025 Results: Final data from P3 COAST-1 and COAST-2 trials for atopic dermatitis in H1 2026

P3 data • Atopic Dermatitis

A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Participants Aged 12 Years and Older With Moderate-to-severe Atopic Dermatitis (COAST 2) (clinicaltrials.gov) - P3 | N=589 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

HYDRO: A Study to Investigate Vaccine Responses in Subcutaneous Amlitelimab Treated Atopic Dermatitis Participants Aged 18 Years and Older Compared With Placebo (clinicaltrials.gov) - P2 | N=224 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Impact of amlitelimab on lichenification in atopic dermatitis: post-hoc results from the STREAM-AD phase 2b study of moderate-to-severe Atopic dermatitis (CDA 2025) - P2 | "In Part 1, adult participants with moderate-to-severe AD were randomized 1:1:1:1:1 to subcutaneous amlitelimab (250 mg with 500-mg loading dose [250 mg+LD], n=77; 250 mg, n=78; 125 mg, n=77; 62.5 mg, n=79) or placebo every 4 weeks (n=79). At Week 24, amlitelimab improved EASI lichenification scores across all body regions. Amlitelimab may be an effective future treatment for moderate-to-severe AD characterized by lichenification."

P2b data • Retrospective data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4