amlitelimab IV (SAR445229) / Sanofi - LARVOL DELTA

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

Outcomes Following Discontinuation of Systemic Immunomodulatory Therapies in Adults with Atopic Dermatitis: A Systematic Review (EADV 2025) - "Six studies examined biologic agents (amlitelimab, dupilumab (2 studies), tralokinumab, rezpegaldesleukin, rocatinlimab) and three evaluated JAK inhibitors (baricitinib, abrocitinib, upadacitinib). Emerging evidence suggests that sustaining disease control following discontinuation of systemic immunomodulatory therapy is possible in some adults with AD. Differences in outcomes between therapies may reflect variations in drug mechanisms or study design. To confidently identify individuals who may benefit from treatment discontinuation, further studies are required with harmonised outcomes (e.g."

Clinical • Immunomodulating • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

Outcomes Following Discontinuation of Systemic Immunomodulatory Therapies in Adults with Atopic Dermatitis: A Systematic Review (EADV 2025) - "Six studies examined biologic agents (amlitelimab, dupilumab (2 studies), tralokinumab, rezpegaldesleukin, rocatinlimab) and three evaluated JAK inhibitors (baricitinib, abrocitinib, upadacitinib). Emerging evidence suggests that sustaining disease control following discontinuation of systemic immunomodulatory therapy is possible in some adults with AD. Differences in outcomes between therapies may reflect variations in drug mechanisms or study design. To confidently identify individuals who may benefit from treatment discontinuation, further studies are required with harmonised outcomes (e.g."

Clinical • Immunomodulating • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

APG990, a monoclonal antibody targeting OX40L, demonstrates safety and an extended half-life in healthy subjects (EADV 2025) - "In preclinical studies, APG990 showed a longer half-life than amlitelimab in nonhuman primates and similar in vitro binding affinity and potency. APG990 was well tolerated across dose groups and exhibited a PK profile that may support evaluation of every 3- to 6-month dosing. These results support further clinical investigations with APG990, including in combination with other monoclonal antibodies, for the treatment of inflammatory conditions such as atopic dermatitis."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Women's Health • TNFSF4

Preclinical Characterization of a Potent and Half-life Extended Anti-OX40L Antibody (EADV 2025) - "In a pharmacokinetic study in rhesus monkeys, HXN-1021 shows a half- life of about 20 days, significantly longer than that of Amlitelimab analogue, which shows a half-life of approximately 10 days in the same study... HXN-1021 is a potentially best-in-class anti-OX40L antibody, showing strong efficacy both in vitro and in vivo. Combining with its extended half-life, HXN-1021 could offer sustained therapeutic benefits, with less frequent dosing scheme, to patients with atopic dermatitis and other inflammatory and autoimmune diseases. IND- enabling studies of HXN-1021 are currently underway."

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

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 (EADV 2025) - P2, P2/3 | "In this RIVER-AD phase 2/3 interim safety analysis of adult participants with moderate-to-severe AD originally from the phase 2b STREAM-AD trial, amlitelimab 250 mg Q4W demonstrated an acceptable safety profile generally consistent with what was previously reported in STREAM-AD."

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

Development and characterization of IAR129, a novel bispecific antibody co-blocking IL-4Ra and OX40L for atopic dermatitis (EADV 2025) - "IAR129 is a first-in class IL4R and OX40L bispecific antibody with half life extension. It potently blocks IL-4, IL-13 and OX40L in vitro comparable to dupilumab and amlitelimab. It shows combinatorial activity superior to single blockade in DC-T coculture, and is highly effective in suppressing both airway inflammation and atopic dermatitis in mice."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Respiratory Diseases • IL13 • IL2 • IL4R • IL5 • TNFSF4 • TSLP

Online Education Significantly Improved Dermatologists' Knowledge Of The Mode Of Action And Key Clinical Data On Emerging Therapies For Atopic Dermatitis That Target The OX40-OX40 Ligand Pathway. (EADV 2025) - "Dermatologists significantly improved their knowledge of survival of pathogenic T cells as a key consequence of OX40-OX40L interaction in the pathogenesis of AD (17% pre- vs 43% post-activity; P <.001), the mode of action of amlitelimab and rocatinlimab (21% pre- vs 55% post-activity; P <.001) and clinical data for these novel therapies (54% pre- vs 74% post-activity; P <.001). This online activity significantly improved dermatologists' understanding of the role of the OX40-OX40L pathway in the pathogenesis of AD and of emerging biologic therapies targeting this pathway. Although there was significant knowledge improvement for all questions, the post test scores of 43% to 74% indicate that dermatologists would benefit from additional education to embed their knowledge of emerging biologic therapies targeting this pathway in AD."

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

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

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

Disproportionate quality of life decline and unaddressed limitations in amlitelimab atopic dermatitis trial. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

HEOR • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Amlitelimab, an anti-OX40 ligand antibody, for atopic dermatitis: a plain language summary of STREAM-AD clinical study. (PubMed, Immunotherapy) - No abstract available

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

In Vitro Evidence Demonstrating the Nondepleting Mechanism of Action of Amlitelimab, an OX40 Ligand Monoclonal Antibody. (PubMed, Acta Derm Venereol) - No abstract available

Journal • Preclinical

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

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

68-week safety results of amlitelimab in participants with moderate-to-severe atopic dermatitis from STREAM-AD Phase 2b dose-ranging and withdrawal study (CDA 2025) - P2 | "Part 1 involved 24-week treatment period of 388 participants with subcutaneous amlitelimab (250 mg with 500 mg loading dose [250mg +LD], n=77; 250mg, n=78; 125mg, n=77; 62.5mg, n=78) or placebo (n=78) every 4 weeks. 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

The keyhole limpet hemocyanin (KLH) challenge model to establish early clinical proof-of-mechanism of investigational drugs for auto-immune diseases. (EULAR 2025) - "Next steps include further exploration of the translation of the KLH model from HV to rheumatoid arthritis (RA) patients by investigating the KLH response in treatment naïve RA patients that are starting methotrexate (MTX) therapy in responders compared to non-responders to MTX therapy. Early phase proof-of-mechanism studies help to elucidate the pharmacological mechanism of action of novel drugs in vivo , and establish the dose-response relationship. Our studies demonstrate that KLH drives an antigen-specific immune response in man in vivo , displaying Th1, Th2 and Th17 characteristics. Our KLH model allows evaluation of systemic antigen-specific responses but also in peripheral tissue."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IFNG • IL13 • TNFSF4

Amlitelimab Reduces Th2-, Th1-, and Th17/22-Related Gene Expression and Protein Levels in Adults With Moderate-to-Severe Atopic Dermatitis: Results From an Exploratory Analysis of the Phase 2b STREAM-AD Study (EAACI 2025) - P2 | "In Part 1, adults with moderate-to-severe AD were randomized to receive subcutaneous amlitelimab (250mg + 500-mg loading dose, 250mg, 125mg, or 62.5mg) or placebo every 4W. It also reduced protein levels associated with Th17/22-related inflammation including the proinflammatory cytokine IL-32 (p<0.001). Conclusion Amlitelimab significantly normalized/reduced genes and proteins associated with AD inflammation in adults with moderate-to-severe AD, further supporting OX40L blockade as a relevant target for treating AD-related inflammation."

Clinical • IO biomarker • P2b data • Atopic Dermatitis • Dermatitis • Immunology • CXCL10 • CXCL9 • IL32 • TNFSF4

Biologics targeting OX40 and OX40L for treatment of atopic dermatitis have distinct inhibitory binding mechanisms (SID 2025) - "Our results provide initial prediction and analysis of the epitopes of OX40 and OX40L targeted biologics emerging for AD treatment. Rocatinlimab and amlitelimab appear to directly inhibit OX40-OX40L interactions via steric occlusion, with amlitelimab also possibly inhibiting OX40L trimer formation, whereas telazorlimab more specifically disrupts a critical intermolecular interaction."

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

Amlitelimab reduces atopic dermatitis-related gene expression elevated in lesional skin: An analysis of the phase 2b STREAM-AD study (SID 2025) - P2 | "Amlitelimab led to downregulation of Th1 (eg, CXCL9 and CXCL10; P<0.05), Th2 (eg, CCL13 and CCL18; P<0.05), and Th17/22 (eg, S100A8 and S100A9; P<0.05) pathway-associated genes in lesional skin at Wk16 compared with baseline, and a greater % recovery toward nonlesional gene expression levels than placebo. The observed normalization of AD-related genes in lesional skin after 16wks of amlitelimab treatment supports the clinical improvements seen in AD lesions in STREAM-AD."

IO biomarker • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CCL18 • CXCL10 • CXCL9 • S100A8 • S100A9

OX40/OX40L as a Therapeutic Target in Atopic Dermatitis: A Scoping Review. (PubMed, Biologics) - "Moreover, early basic and clinical research has shown encouraging results regarding the efficacy and safety of therapies targeting the OX40-OX40L axis in moderate-to-severe AD. Therefore, herein we aim to summarize the current evidence regarding the efficacy and safety of inhibiting the OX40/OX40L signaling axis in patients with moderate-to-severe AD."

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

Safety and Efficacy of Anti-OX40 Therapies in Atopic Dermatitis: A Systematic Review and Meta-Analysis. (PubMed, Dermatitis) - "We aimed to systematically evaluate the efficacy and safety of anti-OX40 therapies (amlitelimab, rocatinlimab, and telazorlimab) in moderate-to-severe AD. In conclusion, anti-OX40 therapies demonstrate clinically meaningful efficacy and an acceptable safety profile for moderate-to-severe AD, offering a potential alternative for patients with inadequate responses to current treatments. Further research is warranted to confirm these results and to refine optimal dosing strategies."

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

Investigating Efficacy of Atopic Dermatitis Systemic Therapeutics After Discontinuation Part I: Biologics. (PubMed, J Clin Aesthet Dermatol) - "Five clinical trial programs met our inclusion criteria, each investigating a different biologic: dupilumab, tralokinumab, lebrikizumab, amlitelimab, and rocatinlimab. The variability in eligibility criteria, treatment durations, and withdrawal periods across trials presents a major challenge in assessing biologics for AD, complicating the comparison of their sustained responses in the absence of head-to-head studies. This heterogeneity, combined with factors such as disease duration and prior use of systemic medications before trial enrollment, hampers the identification of key pathways in AD pathogenesis and impedes efforts to better understand and characterize the disease."

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

Interim results of RIVER-AD: 28-week open-label safety and efficacy of amlitelimab in patients with atopic dermatitis not initially achieving clinical response at Week 24 of the STREAM-AD phase 2b trial (AAD 2025) - P2/3 | "This interim analysis evaluated safety, change in EASI, EASI-75, EASI-90, and IGA 0/1 response following 28-weeks of subcutaneous amlitelimab 250mg every-4-weeks (Q4W) in RIVER-AD in participants not achieving clinical response at Week 24 of STREAM-AD with amlitelimab or placebo. Interim RIVER-AD results demonstrated clinical improvements after 28 weeks of subcutaneous 250mg Q4W amlitelimab treatment in participants with moderate-to-severe AD not achieving clinical response at Week 24 of STREAM-AD, with a safety profile similar to that observed in STREAM-AD."

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

Impact of amlitelimab (an anti-OX40 Ligand antibody) on maintenance of itch response in atopic dermatitis: results from the 52-week STREAM-AD Phase 2b study (AAD 2025) - P2 | "In the STREAM-AD Phase 2b trial, many patients treated with amlitelimab who demonstrated skin improvements also experienced improvements in itch at Week 24. A majority of the clinical responders who saw itch reduction at Week 24 maintained this reduction on- or off-amlitelimab for the 28-week withdrawal period, demonstrating durable and sustained itch responses following amlitelimab treatment."

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