amlitelimab IV (SAR445229) / Sanofi - LARVOL DELTA

Prediction of the efficacy of extended dosing of amlitelimab (an anti-OX40 Ligand antibody) in patients with moderate-to-severe atopic dermatitis using a modeling approach (EADV 2024) - "The PopPK/PD-EASI model simulations support the Q12W extended dose regimen for Phase 3 studies, demonstrating 250mg Q12W +LD predicts similar exposures and efficacy in the range of Q4W dosing regimens evaluated in the STREAM-AD Phase 2b trial."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • 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) vs placebo in patients with moderate-to-severe atopic dermatitis: Study design of phase 3 OCEANA clinical trials COAST 1/2, SHORE, AQUA, and ESTUARY (EADV 2024) - "Results should provide further evidence demonstrating the efficacy and safety of** amlitelimab in treating moderate-to-severe AD using two different dosing regimens, including an extended dosing regimen, in patients with various treatment histories."

Clinical • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus • TNFSF4

In vitro evidence demonstrating the nondepleting mechanism of action of amlitelimab, an OX40 Ligand monoclonal antibody (EADV 2024) - "Activated T cells and Tregs remained intact upon amlitelimab treatment, whereas OX40-expressing activated CD4 T cells and Tregs were found to be depleted via ADCC upon treatment with anti-OX40 antibodies. These antibodies also led to a reduction in the percentage of live Tregs. Furthermore, no ADCC activity was observed against hOX40L-transfected HEK cells with amlitelimab, suggesting a nondepleting mechanism of action for amlitelimab."

IO biomarker • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CD4 • FOXP3 • IL2RA • IL7R • 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

A Comprehensive Review of Biologics in Phase III and IV Clinical Trials for Atopic Dermatitis. (PubMed, J Clin Med) - "There have been 76 clinical trials identified concerning biologic drugs: dupilumab (34 trials), lebrikizumab (14 trials), tralokinumab (10 trials), rocatinlimab (7 trials), amlitelimab (2 trials), nemolizumab (6 trials), MG-K10 (1 trial), CM310 (1 trial), 611 (1 trial). The safety and efficacy of these biologics are comprehensively addressed in this review. This comprehensive review aims to explore the current landscape of biologic therapies for AD, delving into the latest research findings, clinical trial outcomes, and the diverse mechanisms of action employed by these novel interventions."

Journal • P3 data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Sanofi (SNY.US)’s Class 1 new drug amlitelimab has been approved for clinical use in China to treat severe alopecia areata [Google translation] (Sina Corp) - "On July 29, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that Sanofi's (SNY.US) Class 1 new drug amlitelimab injection was approved for clinical use for the treatment of severe alopecia areata...The approval of the clinical trial for severe alopecia areata means that Sanofi will soon conduct clinical research on alopecia areata patients in China."

New 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

Development and characterization of STAR-0310: a novel OX40 antagonistic monoclonal antibody (EAACI 2024) - "STAR-0310 is being compared to telazorlimab, rocatinlimab, and amlitelimab in detailed preclinical pharmacology studies including in vitro potency of T cell proliferation inhibition, cytotoxicity effects on activated T cells and regulatory T cells. Conclusion STAR-0310, an anti-OX40 antibody, demonstrates the potential for increased half-life, high-potency T cell inhibition, and reduced toxicities with minimized effector (ADCC) functions. These promising preclinical findings support the potential use of STAR-0310 in moderate-to-severe AD and other immunologic diseases."

Atopic Dermatitis • Dermatitis • Immunology • TNFSF4

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

Submit Preliminary Analysis Of Primary Data Of Subjects Above 18 Years In India: CDSCO Panel Tells Sanofi On Amlitelimab Study (Medical Dialogues) - "After considering the phase III clinical study protocol of the monoclonal antibody Amlitelimab in the treatment of moderate-to-severe Atopic Dermatitis, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the drug major Sanofi to submit the preliminary analysis of primary data of subjects above 18 years..."

Clinical protocol • Atopic Dermatitis • Immunology

Amlitelimab improves extent and severity of disease in adults with moderate-to-severe atopic dermatitis (AD): 24-week results from a Phase 2b trial (STREAM-AD) (EADV-Sp 2024) - P2 | "Amlitelimab improved metrics of disease extent and severity in adults with moderate-to-severe AD in the first 24 weeks of this Phase 2b trial, with greatest improvement seen in the 250 mg plus LD arm."

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

Improvements on patient-reported outcome (PRO) measures with 24 weeks of amlitelimab treatment in adults with moderate-to-severe atopic dermatitis: results from a Phase 2b trial (STREAM-AD) (EADV-Sp 2024) - P2 | "Amlitelimab improved metrics of disease severity, disease control, and QoL, with the greatest improvement seen in the 250 mg with LD arm."

Clinical • P2b data • Patient reported outcomes • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Efficacy and safety of amlitelimab (an OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 52-week results from a Phase 2b Trial (STREAM-AD) (EADV-Sp 2024) - P2 | "Maintenance of clinical responses were demonstrated for 28 weeks in the majority of patients, both on- and off- amlitelimab."

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

Emerging drugs for the treatment of atopic dermatitis: a focus on phase 2 and phase 3 trials. (PubMed, Expert Opin Emerg Drugs) - "Clinical trials for 36 agents currently in phase 2 or phase 3 are evaluated with particular focus on the studies for, B244, CBP-201, Tapinarof, Lebrikizumab, Nemolizumab, Amlitelimab, and Rocatinlimab as they explore novel pathways and have some of the most promising results. These clinical trials contribute to the evolution of AD treatment toward greater precision based on salient pathways with a particular focus on moderate-to-severe AD to enhance efficacy and minimize adverse effects."

Journal • P2 data • P3 data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pediatrics

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

Regulatory • Atopic Dermatitis • Dermatology • Immunology

Efficacy and safety of amlitelimab (an OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 52-week results from a Phase 2b trial (STREAM-AD) (AAD 2024) - No abstract available

Clinical • Late-breaking abstract • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Improvements on patient-reported outcome (PRO) measures with 24 weeks of amlitelimab treatment in adults with moderate-to-severe atopic dermatitis: results from a Phase 2b trial (STREAM-AD) (AAD 2024) - P2 | "Amlitelimab improved metrics of disease severity, disease control, and QoL, with the greatest improvement seen in the 250 mg with LD arm."

Clinical • P2b data • Patient reported outcomes • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Amlitelimab improves extent and severity of disease in adults with moderate-to-severe atopic dermatitis (AD): 24-week results from a Phase 2b trial (STREAM-AD) (AAD 2024) - P2 | "Amlitelimab improved metrics of disease extent and severity in adults with moderate-to-severe AD in the first 24 weeks of this Phase 2b trial, with greatest improvement seen in the 250 mg plus LD arm."

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

Amlitelimab: Regulatory submission for atopic dermatitis in 2026 and beyond (Sanofi) - Q4 & FY2023 Results

Regulatory • Atopic Dermatitis • Immunology

OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target. (PubMed, Am J Clin Dermatol) - "As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD."

IO biomarker • Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • Pain • Pruritus • TNFA • TNFRSF4 • TNFSF4

The Scleroderma Research Foundation Announces the Launch of the CONQUEST Trial Platform and IND Clearance (PRNewswire) - "Sanofi and Boehringer Ingelheim share the platform; patient enrollment to begin early in 2024...The Scleroderma Research Foundation (SRF)...announced that the FDA has cleared its Investigational New Drug application (IND) to launch the CONQUEST clinical trial platform and begin enrolling patients. Sanofi and Boehringer Ingelheim will each contribute an experimental agent to CONQUEST, and as such they are the first pharma partners to commit to this protocol designed to efficiently advance new scleroderma treatments through clinical development. The first two nominated investigational drugs will be evaluated for safety and efficacy in scleroderma patients burdened by interstitial lung disease (SSc-ILD). The Sanofi agent is amlitelimab, a non-depleting monoclonal antibody that binds to OX40-Ligand; the Boehringer Ingelheim agent is BI -1015550, an oral PDE-4B inhibitor....The CONQUEST platform will be open to adding additional investigational agents starting in 2025."

IND • New trial • Immunology • Interstitial Lung Disease • Scleroderma

Efficacy and safety of amlitelimab (an anti-OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 24-week results from a Phase 2b trial (STREAM-AD) (RAD-Virtual 2023) - P2 | N=390 | STREAM-AD (NCT05131477) | Sponsor: Kymab Limited | "In this dose-ranging Phase 2b trial of amlitelimab in adults with moderate-to-severe AD, amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups."

P2b data