amlitelimab IV (SAR445229) / Sanofi - LARVOL DELTA

The "OX40 Paradox": A Systematic Review Investigating the Temporal Lag in Clinical Response for OX40/OX40L Inhibitors (Amlitelimab, Rocatinlimab)-Defining a New "Induction-Maintenance" Sequence Model (EADV 2026) - No abstract available

Clinical • Review • TNFSF4

Effect of amlitelimab, a non-depleting anti-OX40 ligand antibody, on vaccine antibody responses in adult participants with moderate-to-severe atopic dermatitis: Results from HYDRO Phase 2 trial (EADV 2026) - No abstract available

Clinical • P2 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Safety of amlitelimab in moderate-to-severe atopic dermatitis: Integrated analysis from the OCEANA clinical program (EADV 2026) - No abstract available

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Sanofi has retreated from a plan to file its anti-OX40L antibody amlitelimab for approval as a treatment for atopic dermatitis (AD) and will abandon development of the drug in this indication. (pharmaphorum) - "The decision, announced this morning, comes despite Sanofi's assertions earlier this year that it planned to file amlitelimab in AD on the strength of the phase 3 SHORE and COAST studies...The company now says that the 'totality of efficacy and safety evidence' generated for amlitelimab to date suggests there is no point continuing to develop the drug in AD, despite a clear dosing advantage over Dupixent, with four injections a year versus every two to four weeks."

Discontinued • Atopic Dermatitis • Immunology

The OX40-OX40L Co-Stimulatory Pathway as a Shared Driver of Immune Persistence in Skin and Airway Inflammation. (PubMed, Clin Rev Allergy Immunol) - "Therapeutic targeting of this pathway, particularly with monoclonal antibodies such as amlitelimab, has demonstrated clinically meaningful efficacy and suggests potential for durable disease modification. The OX40-OX40L axis represents an important immunological pathway linking epithelial activation to adaptive immune memory across barrier tissues. Its role in sustaining immune persistence provides a conceptual framework for understanding chronic inflammatory diseases and supports continued investigation of therapies targeting upstream co-stimulatory pathways."

IO biomarker • Journal • Review • Allergic Rhinitis • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Fibrosis • Immunology • Inflammation • Nasal Polyps • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • IL33 • TNFSF4 • TSLP

Is Kaposi's sarcoma the end of the OX40/OX40L axis in atopic dermatitis? (PubMed, Front Immunol) - "The discontinuation of rocatinlimab after confirmed and suspected cutaneous Kaposi's sarcoma cases, together with two cumulative cases reported in the amlitelimab program in patients with known risk factors, has changed the discussion from early promise to mechanism, risk, and therapeutic strategy. The central challenge is now to determine how the axis can be targeted, in which patients, and in what therapeutic context, to maximize clinical benefit while managing risk. Rather than signaling the end of the axis in atopic dermatitis, Kaposi's sarcoma may instead mark the limits of a first-generation development strategy and the beginning of a more selective approach built around molecule design, therapeutic context, and prospective risk mitigation."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor • TNFSF4

Preliminary baseline characteristics of participants randomized into the ongoing Phase 2b CONQUEST trial for interstitial lung disease associated with systemic sclerosis (EULAR 2026) - P2 | "Methods CONQUEST is a global, multicenter, double-blind, randomized, placebo-controlled, Phase 2b platform trial investigating the efficacy and safety of amlitelimab vs placebo and nerandomilast vs placebo to treat early active SSc with ILD [3]...Background immunosuppressive therapy (≤1 therapy) is allowed as follows: mycophenolate, methotrexate, or azathioprine for ≥4 months without dose adjustments in the last 2 months prior to randomization (temporary withholding for ≤14 days is allowed for treatment of infections and other adverse events); hydroxychloroquine at a stable dose for ≥6 weeks prior to randomization; and oral corticosteroids equivalent to 10 mg/d prednisone if started ≥2 weeks prior to randomization...Conclusions Participants in CONQUEST are representative of SSc with ILD patients seen in clinical practice, apart from enrolling a higher percentage of patients with limited/sine cutaneous SSc with ILD, which is likely reflective of the trial design...."

Clinical • P2b data • Fibrosis • Immunology • Infectious Disease • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

OX40/OX40L modulation: A target for regulating T cells in cutaneous inflammatory disorders. (PubMed, J Eur Acad Dermatol Venereol) - "Studies of amlitelimab and rocatinlimab have shown some efficacy but have demonstrated increased durability of response. Current concerns with the class are the potential for broad immune suppression with antagonists and the potential for worsening disease with agonists. Additional studies will enable us to determine their benefit-risk ratio in the real-world setting."

Journal • Review • Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Psoriasis • TNFSF4

AI-Guided Generation and Preclinical Evaluation of an OX40L-IL31 Bispecific Antibody (AAD 2026) - "It potently inhibits IL31 activity in IL31R-STAT and HaCaT assays, outperforming Nemolizumab and NM26-2198 analogues. Meanwhile, HXN-1022 exhibits robust in vitro activity for OX40L in the OX40-NFκB reporter assay, OX40L-induced PBMC activation, and Th2 differentiation experiments, with potency comparable to Amlitelimab... HXN-1022 is a first-in-class bsAb that simultaneously targets IL-31 and OX40L, two key drivers of inflammation and pruritus in skin disease. These findings support HXN-1022 as a promising therapeutic candidate for AD and other autoimmune skin disorders. HXN-1022 is currently under IND-enabling studies."

Bispecific • Preclinical • Atopic Dermatitis • Dermatitis • Graft versus Host Disease • Immunology • Inflammation • Pruritus • IL1R1 • TNFSF4

Preclinical Characterization of a Potent and Half-life Extended Anti-OX40L Antibody (AAD 2026) - "In a pharmacokinetics study, HXN-1021 showed a half-life of about 20 days, significantly longer than that of an Amlitelimab analogue, which showed a half-life of approximately 10 days in the same study. HXN-1021 is a next-generation, long-acting anti-OX40L antibody with the potential to deliver durable therapeutic benefit in atopic dermatitis and other inflammatory or autoimmune diseases. IND-enabling studies are in progress."

Preclinical • Atopic Dermatitis • Dermatitis • Graft versus Host Disease • Immunology • TNFSF4

INC04 Unlocking the Potential of OX40 Ligand Pathway in AD: Targeting the Inflammatory Prequel (AAD 2026) - "Highlight the importance of the OX40 ligand pathway in driving the inflammatory prequel of AD 3. Explore future treatment goals in AD, including sustained efficacy off-therapy, and explore the most recent amlitelimab Phase 3 data in AD"

Atopic Dermatitis • Dermatitis • Immunology

Biologic Monotherapies for Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Bayesian Network Meta-Analysis of Established and Investigational Agents. (PubMed, Cureus) - "This Bayesian network meta‑analysis (BNMA) provides the first unified evaluation of all biologic monoclonal antibodies approved as monotherapy for AD (dupilumab, lebrikizumab, tralokinumab) together with emerging immunotherapies, including amlitelimab, rademikibart, rezpegaldesleukin, rocatinlimab, telazorlimab, temtokibart, and zumilokibart, across key efficacy measures.  A PRISMA‑2020-compliant systematic review and PROSPERO‑registered protocol (CRD420251162704) identified phase 2-3 randomized, double‑blind, placebo‑controlled trials reporting week‑16 outcomes (week‑24 for rocatinlimab). Zumilokibart, rademikibart, and temtokibart emerge as additional candidates with encouraging activity, whereas telazorlimab showed limited clinical benefit. Collectively, these findings provide a comprehensive comparative framework to inform biologic selection and therapeutic sequencing."

Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Dupilumab Outperforms Approved and Investigational Biologic Monotherapies in Moderate-to-Severe Atopic Dermatitis (AAD 2026) - " Seventeen RCTs (n=5508) compared dupilumab, tralokinumab, lebrikizumab, rocatinlimab, amlitelimab and rezpegaldesleukin with placebo at week 16 (rocatinlimab 300mg, 24 weeks). Dupilumab 300mg was the most effective biologic for moderate-to-severe AD, achieving both the strongest relative efficacy and the highest SUCRA ranking. Lebrikizumab emerged as a close second, particularly for itch improvement."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology

The OX40/OX40L Axis Promotes Th2 Activity and Impairs Regulatory T Cell Function in Atopic Dermatitis. (PubMed, Allergy) - "AD patients exhibit significant upregulation of OX40 expression in effector and regulatory CD4+ T cells. Both subsets interact with OX40L-expressing cells in the skin, leading to the promotion of skin inflammation by downregulation of function and anti-inflammatory capacity of Tregs."

IO biomarker • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • CD4 • IL10 • TNFRSF4 • TNFSF4

AI-Guided Generation and Preclinical Evaluation of an OX40L-IL31 Bispecific Antibody (AAAAI 2026) - "It effectively inhibits IL31 biological activity in the IL31R-STAT reporter assay and HaCaT cell activation, with superior efficacy to the benchmarks, Nemolizumab and NM26-2198 analogs. For the OX40L arm, HXN-1022 significantly blocks OX40L-induced downstream signaling and PBMC activation, with potency comparable to Amlitelimab...The bsAb represents a highly promising therapeutic option for patients with autoimmune skin disorders. HXN-1022 is currently under IND-enabling studies."

Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Graft versus Host Disease • Immunology • Inflammation • Pruritus • IL1R1 • TNFSF4

ADVANCING DRUG DEVELOPMENT FOR SYSTEMIC SCLEROSIS BY PRIORITISING FINDINGS FROM HUMAN GENETIC ASSOCIATION STUDIES (SSWC 2026) - "Amlitelimab (anti-OX40L monoclonal antibody) is currently being explored in CONQUEST, a multicentre randomised controlled platform trial for SSc-ILD... Our systematic approach, combining evidence from different bioinformatics platforms, has identified drug opportunities for repurposing/druggable targets for SSc. A novel and unexpected finding was the identification of multiple neurotransmitter-targeting drug therapies, particularly relevant to SSc-related Raynaud's phenome- non and gastrointestinal involve- ment. Future studies of these candi- dates for SSc drug repurposing are indicated; many of which are widely available/ and often inexpensive."

CNS Disorders • Immunology • Movement Disorders • Scleroderma • Systemic Sclerosis • TNFSF4

Amlitelimab (an Anti-ox40 Ligand Antibody) Significantly Reduces Blood Biomarkers Involved in the Pathogenesis of Asthma (ATS 2026) - No abstract available

Biomarker • IO biomarker • Asthma • Immunology • Respiratory Diseases

Long Acting Bispecific Antibody Co-blocking OX40L and TNFα for Hidradenitis Suppurativa (AAAAI 2026) - "In human DC/T cell coculture assay, LQ095 synergistically suppressed GM-CSF production, better than adalimumab, amlitelimab and oxelumab analogue. In cynomolgus monkeys, LQ095 exhibited favorable PK profile with half-life extended to 2-3 times compared to traditional monoclonal antibodies. Conclusions The impressive in vitro and in vivo activity data of LQ095 make it a very promising therapy for HS treatment."

Late-breaking abstract • Dermatology • Graft versus Host Disease • Hidradenitis Suppurativa • Immunology • CSF2 • IL17A • IL2 • TNFA • TNFSF4

Preclinical Characterization of a Potent and Half-life Extended Anti-OX40L Antibody (AAAAI 2026) - "In a pharmacokinetics study, HXN-1021 showed a half-life of about 20 days, significantly longer than that of an Amlitelimab analogue, which showed a half-life of approximately 10 days in the same study. Conclusions HXN-1021 is a next-generation, half-life extended anti-OX40L antibody that has the potential to provide sustained therapeutic benefits for patients with atopic dermatitis and other inflammatory and autoimmune diseases. IND-enabling studies for HXN-1021 are currently underway."

Preclinical • Atopic Dermatitis • Dermatitis • Graft versus Host Disease • Immunology • TNFSF4

Long Acting Bispecific Antibody Co-blocking OX40L and TNFα for Hidradenitis Suppurativa (AAAAI 2026) - "In human DC/T cell coculture assay, LQ095 synergistically suppressed GM-CSF production, better than adalimumab, amlitelimab and oxelumab analogue. The impressive in vitro and in vivo activity data of LQ095 make it a very promising therapy for HS treatment."

Dermatology • Graft versus Host Disease • Hidradenitis Suppurativa • Immunology • CSF2 • IL17A • IL2 • TNFA • TNFSF4

Advancing drug development for systemic sclerosis by prioritising findings from human genetic association studies. (PubMed, Rheumatology (Oxford)) - "Our systematic approach, combining evidence from different bioinformatics platforms, has identified drug opportunities for repurposing/druggable targets for SSc. A novel and unexpected finding was the identification of multiple neurotransmitter-targeting drug therapies, particularly relevant to SSc-related Raynaud's phenomenon and gastrointestinal involvement. Future studies of these candidates for SSc drug repurposing are indicated; many of which are widely available and often inexpensive."

Journal • Cardiovascular • Hematological Disorders • Immunology • Rheumatology • Scleroderma • Systemic Sclerosis • TNFSF4

Molecular differentiation of OX40 and OX40L targeted biologics using AlphaFold3 and molecular dynamics simulations. (PubMed, J Invest Dermatol) - "Our analysis suggests rocatinlimab and amlitelimab directly inhibit OX40-OX40L interactions by physically blocking the cognate OX40-OX40L interface via steric occlusion, whereas telazorlimab disrupts a critical OX40-OX40L bond. Together, this work provides molecular characterization of the epitopes of OX40 and OX40L targeted biologics emerging in dermatology."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

Novel Therapeutic Strategies for Atopic Dermatitis: Biomarker Modulation and Clinical Implications. A Systematic Review. (PubMed, Clin Rev Allergy Immunol) - "Dupilumab was the most extensively investigated therapy, followed by tralokinumab, JAK inhibitors, and novel agents such as amlitelimab, stapokibart, and tezepelumab...CCL17 and LDH currently represent the most reliable biomarkers associated with disease severity and treatment response, although their limited specificity restricts clinical applicability. Future research should aim to validate integrated biomarker panels combining immunologic, transcriptomic, and microbiomic data to enable precision medicine approaches in atopic dermatitis management."

Biomarker • Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

The Role of OX40 Pathway Inhibition as a New Therapeutic Strategy for Atopic Dermatitis. (PubMed, BioDrugs) - "Amlitelimab, an anti-OX40L monoclonal antibody, has demonstrated sustained efficacy and a favorable safety profile in phase IIa and IIb trials. Rocatinlimab, targeting OX40, has also shown promising results in a phase IIb study and has progressed into multiple phase III trials, with supportive top-line data. In contrast, telazorlimab has shown more modest efficacy and has not advanced to later-stage development. Next-generation agents, including IMG-007, STAR-0310, APG990, and APG279, have been engineered with extended half-lives and attenuated antibody-dependent cellular cytotoxicity to support longer dosing intervals and improve tolerability. While these findings are encouraging, direct comparative studies among agents and versus established therapies are lacking, and long-term efficacy and safety data are still needed. This narrative review explores the role of the OX40/OX40L axis in atopic dermatitis pathogenesis and critically evaluates emerging therapies targeting..."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

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 primary endpoint, percentage change in EASI score at week 16, was met. In this post hoc analysis, EASI subscores using least-squares mean percentage change from baseline were assessed at week 24. Data on or after treatment discontinuation or use of rescue or prohibited medications were considered missing and were imputed by worst observation carried forward."

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