amlitelimab SC (KY1005 SC) / Sanofi - LARVOL DELTA

Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis. (PubMed, J Allergy Clin Immunol) - P2 | "Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through Week 52. Sustained responses were observed in the majority of patients after amlitelimab withdrawal for 28 weeks."

Clinical • IO biomarker • Journal • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Adult Participants With Severe Alopecia Areata (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Sanofi | Trial completion date: Feb 2026 ➔ Feb 2028

Monotherapy • Trial completion date • Alopecia • Dermatology • Immunology

Amlitelimab SC: Data readout from P2 TIDE-asthma trial (NCT05421598) for asthma in H1 2025 (Sanofi) - Q3 2024 Results

P2 data • Asthma • Immunology

Impact of amlitelimab (an anti-OX40 Ligand antibody) on atopic dermatitis of the head and neck: post hoc results from the STREAM-AD phase 2b study of moderate-to-severe atopic dermatitis (EADV 2024) - P2 | "In Part 1, adult participants with moderate-to-severe AD were randomised 1:1:1:1:1 to subcutaneous amlitelimab every 4 weeks (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) . Amlitelimab improved EASI head and neck subscores vs placebo at Week 24, and was effective across all signs (erythema, oedema/papulation, excoriation, and lichenification) of head and neck AD. Amlitelimab may be an effective future treatment option for patients with moderate-to-severe AD with hard-to-treat lesions on the head and neck."

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

Amlitelimab (an anti-OX40 Ligand antibody) normalises the atopic dermatitis gene signature in the skin of patients with moderate-to-severe atopic dermatitis (EADV 2024) - P2 | "In Part 1, adults with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab (250 mg with 500 mg loading dose (LD; n=77), 250 mg (n=78), 125 mg (n=77), or 62.5 mg (n=79)) , or placebo (n=79) every 4 weeks over 24 weeks. Following 16 weeks of treatment with amlitelimab, a normalisation in the AD gene signature was observed in lesional skin compared to baseline, supporting the clinical improvements seen in AD lesions ."

Clinical • Gene Signature • IO biomarker • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus • TNFSF4

68-week safety results of amlitelimab (an anti-OX40 Ligand antibody) in patients with moderate-to-severe atopic dermatitis from STREAM-AD Phase 2b dose-ranging and withdrawal study (EADV 2024) - P2 | "Part 1 involved a 24-week treatment period (last dose at Week 20) with 388 participants treated with subcutaneous amlitelimab or placebo every 4 weeks (Q4W; 250mg with 500mg loading dose (250mg +LD), n=77; 250mg, n=78; 125mg, n=77; 62.5mg, n=78; placebo, n=78) . In the STREAM-AD Phase 2b trial, amlitelimab was well tolerated and demonstrated an acceptable safety profile in the Part 2 (responder) population up to 68 weeks."

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

RIVER-AD: Long-Term Safety and Efficacy Evaluation of Amlitelimab in Participants of Previous Amlitelimab Moderate to Severe Atopic Dermatitis Clinical Trials (clinicaltrials.gov) - P2/3 | N=1310 | Recruiting | Sponsor: Sanofi | Phase classification: P2 ➔ P2/3

Phase classification • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease (clinicaltrials.gov) - P2 | N=204 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Celiac Disease • Immunology

A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease (clinicaltrials.gov) - P2 | N=204 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Celiac Disease • Immunology

RIVER-AD: Long-Term Safety and Efficacy Evaluation of Amlitelimab in Participants of Previous Amlitelimab Moderate to Severe Atopic Dermatitis Clinical Trials (clinicaltrials.gov) - P2 | N=1310 | Recruiting | Sponsor: Sanofi | N=450 ➔ 1310 | Trial completion date: Apr 2028 ➔ Dec 2028 | Trial primary completion date: Oct 2027 ➔ Dec 2028

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

Sanofi Q2: strong performance with 10% sales growth; 2024 guidance upgraded (GlobeNewswire) - "The phase 2 study assessing efficacy and safety of subcutaneous injections of amlitelimab in patients aged 18 years and older with severe alopecia areata enrolled the first patients (clinical study identifier: NCT06444451); The CONQUEST phase 2 study assessing efficacy and safety of subcutaneous injections of amlitelimab in patients aged 18 years and older with systemic sclerosis enrolled the first patients (clinical study identifier: NCT06195072)."

Enrollment open • Atopic Dermatitis • Dermatology • Immunology • Scleroderma • Systemic Sclerosis

Sanofi Q2: strong performance with 10% sales growth; 2024 guidance upgraded (Sanofi Press Release) - "The phase 2 study assessing efficacy and safety of subcutaneous injections of amlitelimab in patients aged 18 years and older with severe alopecia areata enrolled the first patients..."

Enrollment open • Alopecia • Immunology

Amlitelimab SC: Data readout from P2 TIDE-asthma trial (NCT05421598) for asthma in H2 2024 (Sanofi) - Q2 2024 Results: Data readout from P2 trial (NCT06118099) for hidradenitis suppurativa in H1 2025

P2 data • Asthma • Hidradenitis Suppurativa • Immunology

A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Adult Participants With Severe Alopecia Areata (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Alopecia • Dermatology • Immunology

A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Adult Participants With Severe Alopecia Areata (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Sanofi

Monotherapy • New P2 trial • Alopecia • Dermatology • Immunology

CONQUEST: Platform Clinical Study for Conquering Scleroderma (clinicaltrials.gov) - P2 | N=400 | Recruiting | Sponsor: Scleroderma Research Foundation, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Amlitelimab (an OX40 ligand antibody) significantly reduces serum IgE and LDH, and epidermal hyperplasia in adults with moderate-to-severe atopic dermatitis (EAACI 2024) - P2 | "In Part 1, adults with moderate-to-severe AD were randomized 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose [LD; n=77], 250 mg [n=78], 125 mg [n=77], 62.5 mg [n=79]), or placebo (n=79) every 4 weeks over 24 weeks. At Week 16, amlitelimab significantly reduced epidermal thickness (p<0.01) and cytokeratin 16 staining in the epidermis (p<0.001), while epidermal thickness and cytokeratin 16 staining were not significantly reduced in the placebo arm (p=0.71 and p=0.71, respectively). Conclusion Amlitelimab significantly reduced serum total IgE and LDH levels as well as epidermal hyperplasia in adults with moderate-to-severe AD, further supporting that OX40L blockade is a relevant target for the treatment of AD-related inflammation."

Clinical • IO biomarker • Atopic Dermatitis • Dermatitis • Immunology • KRT16 • TNFSF4

Efficacy and safety of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis (AD): a phase 2b trial (STREAM-AD) (EAACI 2024) - P2 | "In Part 1, adult participants were randomized 1:1:1:1:1 to subcutaneous amlitelimab Q4W (250mg with 500mg loading dose [+ LD], n=77; 250mg, n=78; 125mg, n=77; 62.5mg, n=79) or placebo Q4W (n=79). Conclusion Clinically meaningful efficacy with amlitelimab was demonstrated over 52 wks, with an acceptable safety profile. Clinical responses were maintained in most patients 28 wks after treatment discontinuation."

Clinical • IO biomarker • P2b data • Atopic Dermatitis • Dermatitis • Immunology • TNFSF4

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

Monotherapy • New P3 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Amlitelimab: Regulatory submission for atopic dermatitis in 2027 (Sanofi) - Q1 2024 Results

Regulatory • Atopic Dermatitis • Dermatology • Immunology

Amlitelimab: Data readout from P2 trial (NCT06118099) in patients with moderate to severe hidradenitis suppurativa in 2025 (Sanofi) - Q1 2024 Results

P2 data • Hidradenitis Suppurativa • Immunology

Amlitelimab: “Amlitelimab: durable clinical response supports Q12W dosing in atopic dermatitis with safety profile maintained”; Atopic dermatitis (Sanofi) - Q1 2024 Results

P2b data • Atopic Dermatitis • Dermatology • Immunology

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 | N=571 ➔ 901 | Trial completion date: Oct 2027 ➔ Oct 2028 | Trial primary completion date: Oct 2027 ➔ Oct 2028

Enrollment change • Trial completion date • Trial primary completion date • 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=249 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Press Release: New Phase 2b results for amlitelimab support potential for best-in-class maintenance of response in atopic dermatitis (GlobeNewswire) - P2b | N=390 | STREAM-AD (NCT05131477) | Sponsor: Kymab Limited | "Positive results from Part 2 of the investigational amlitelimab Phase 2b study STREAM-AD showed sustained improvement of signs and symptoms for 28 weeks in adults with moderate to severe AD who previously responded to amlitelimab and continued treatment. High responder rates were also observed in participants who were taken off amlitelimab. The safety profile was consistent with Part 1 of the study with amlitelimab being well-tolerated and no new safety concerns identified. These results were presented as part of a late-breaking session at the American Academy of Dermatology (AAD) 2024 Conference in San Diego..."

P2b data • Atopic Dermatitis • Immunology