amlitelimab IV (SAR445229) / Sanofi - LARVOL DELTA

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

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

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

BH17 Bridging the gap: identifying dual-targeting therapies for patients with alopecia areata and coexisting immune-mediated inflammatory diseases. (PubMed, Br J Dermatol) - "For eczema, therapies such as dupilumab show limited evidence in also treating AA...For instance, baricitinib is licensed for both AD and AA, while upadacitinib is licensed for AD and is currently in phase III trials for AA. Amlitelimab, which targets the OX40 ligand pathway, is currently in phase III clinical trials for atopic dermatitis and in phase II trials for severe AA...In psoriasis, overlapping therapies include ustekinumab, approved for psoriasis and being studied for AA. As for patients with RA, tofacitinib is approved for moderate-to-severe disease and is also utilized in AA. Abatacept is a cytotoxic T lymphocyte-associated protein 4 (CTLA4) immunoglobin costimulatory modulator that attenuates the activation of T cells and is widely used in RA...The Global Registry of Alopecia areata disease Severity and treatment Safety (GRASS) UK is a prospective, multicentre, observational clinical registry designed to create harmonized datasets. These datasets aim to..."

Journal • Review • Alopecia • Atopic Dermatitis • CNS Disorders • Crohn's disease • Dermatitis • Dermatology • Gastroenterology • Genetic Disorders • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Multiple Sclerosis • Psoriasis • Rheumatoid Arthritis • Rheumatology • Vitiligo • CTLA4

OX40 Ligand Inhibitors for Moderate-to-Severe Atopic Dermatitis: A Review of Phase II Clinical Trial Data. (PubMed, Skin Therapy Lett) - "On this basis, three phase II clinical trials have been conducted to evaluate the efficacy and safety of three different OX40-OX40L inhibitors (amlitelimab, rocatinlimab, and telazorlimab) in moderate-to-severe AD. Herein, we review the published data from these studies."

Journal • P2 data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • 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

Efficacy and Safety of All Monoclonal Antibodies in Moderate-to-Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis. (PubMed, Pharmacoepidemiol Drug Saf) - "Through the analysis of the primary efficacy indicators, this network meta-analysis (NMA) study indicated that all monoclonal antibodies performed better than placebo. Based on the results of this study, Spesolimab, Rademikibart, Dupilumab, Amlitelimab were recommended treatment options with relatively good efficacy and safety."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

Interim safety results of amlitelimab (anti-OX40 ligand antibody) in participants with moderate-to-severe atopic dermatitis from the RIVER-AD phase 2/3 ongoing open-label study (ISDS 2025) - P2, P2/3 | "No deaths occurred. In conclusion, amlitelimab demonstrated an acceptable safety profile in this interim analysis of RIVER-AD trial, consistent with previous findings from STREAM-AD trial."

Clinical • P2/3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases • TNFSF4

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

The OX40-OX40L Co-stimulatory pathway in dermatology: emerging frontiers for therapeutic approaches. (PubMed, Inflamm Res) - "The complex interplay between mast cells expressing OX40L and T cells expressing OX40, which in some contexts can inhibit regulatory T cell (Treg) function and promote Th17 differentiation, underscores the therapeutic potential of either antagonizing or agonizing this co-stimulatory pathway. In this review, we discuss selected dermatological diseases in which the OX40/OX40L axis appears relevant to their immunopathogenesis and may serve as a potential therapeutic target."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Hidradenitis Suppurativa • Immunology • Oncology • Psoriasis • Urticaria • Vitiligo • CD8 • TNFSF4

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