tomaralimab (NM-101) / Neuramedy - LARVOL DELTA

Advances and challenges in Toll-like receptor-targeted therapy for rheumatoid arthritis. (PubMed, Drug Discov Today) - "Representative agents such as OPN-305, OPN-301, imiquimod, and antidepressants have demonstrated therapeutic potential by modulating TLR signaling in RA pathological manifestations. TollB-001, a novel small molecular drug, represents a potential breakthrough in RA therapy. Despite promising preclinical and clinical outcomes with agents including IMO-3100, DV-1179, and R848, challenges remain regarding efficacy variability and immune-related safety. This review aims to provide insights into TLR-based interventions and inform the development of future strategies for more effective management."

Journal • Review • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Phase 1 Single Ascending Dose Study (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Neuramedy Co. Ltd.

New P1 trial

Therapeutic potential of a systemically applied humanized monoclonal antibody targeting Toll‑like receptor 2 in atopic‑dermatitis‑like skin lesions in a mouse model. (PubMed, Biomed Rep) - "In the present study, it was observed that administrating Tomaralimab through intravenous injection alleviated AD-like skin lesions in BALB/c mice challenged with topical application of 2,4-dinitrochlorobenzene by reducing the infiltration of inflammatory cells into skin lesions and preventing the creation of various inflammatory cytokines, including thymic stromal lymphopoietin, interleukin (IL)-4, IL-13, IL-17 and IL-31, which are associated with the pathogenesis of AD. These findings support the feasibility of using a humanized anti-TLR2 monoclonal Ab as systemic therapy for AD."

Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IL13 • IL17A • TLR2 • TSLP

TLR2-EGR1 signaling axis modulates TGFβ1-induced differentiation of fibroblasts into myofibroblasts in pulmonary fibrosis. (PubMed, Biochem Biophys Res Commun) - "Elevated EGR1 levels were detected in the lung tissues of a bleomycin (BLM)-induced mouse model of pulmonary fibrosis. Moreover, the administration of tomaralimab, an antagonistic anti-TLR2 antibody, reduced the EGR1 expression and collagen deposition. Altogether, targeting the TLR2-EGR1 pathway could be a promising therapeutic approach for pulmonary fibrosis by blocking TGFβ1-induced myofibroblast differentiation."

IO biomarker • Journal • Immunology • Pulmonary Disease • Respiratory Diseases • EGR1 • TGFB1 • TLR2

A Sub Analysis of Clinical Study of Tomaralimab, a Toll-like Receptor 2 (TLR-2) Antibody, in Patients with Lower Risk Myelodysplastic Syndromes (MDS) That Have Received Prior Hypomethylating Agent (HMA) Therapy. (EORTC-NCI-AACR 2024) - "In patients with HMA failure MDS (n = 23), 40.91% patients achieved an ER, and all evaluated (n = 23; 100%) patients had SD at 32 wks, 31.25% achieved ER, and 100% had SD. The study provided a positive benefit–risk profile in the treatment of HMA-failure subjects as monotherapy and in combination with AZA."

Clinical • IO biomarker • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • CD34 • KDM6B • TLR2

TLR2 immunotherapy suppresses neuroinflammation, tau spread, and memory loss in rTg4510 mice. (PubMed, Brain Behav Immun) - "Importantly, treatment with anti-TLR2 monoclonal antibody Tomaralimab blocked TLR2 activation and inflammatory responses in a dose-dependent manner, and significantly reduced tau spread and memory loss in rTg4510 mice. These results suggest that TLR2 plays a crucial role in tau spread by causing aberrant microglial activation in response to pathological tau, and blocking TLR2 with immunotherapy may ameliorate tau pathogenesis in Alzheimer's disease."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Inflammation • TLR2

INHIBITION OF NEURON-TO-OLIGODENDROCYTE ALPHA-SYNUCLEIN PROPAGATION WITH AN ANTI-TLR2 ANTIBODY (ADPD 2024) - "These features were confirmed in the cell and mouse models and were effectively prevented by Tomaralimab. These results suggest that GCIs are formed through neuron-to-oligodendrocyte propagation of a-synuclein via TLR2, and anti-TLR2 immunotherapy could be an effective strategy for disease-modifying therapy for MSA."

IO biomarker • CNS Disorders • Inflammation • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Solid Tumor • TLR2

Single and Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of NM-101 (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Neuramedy Co. Ltd.

New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Unraveling the Tomaralimab Epitope on the Toll-like Receptor 2 via Molecular Dynamics and Deep Learning. (PubMed, ACS Omega) - "Using deep learning-based ΔΔG prediction, we computationally contrasted human TLR2-TLR2, TLR2-TLR1, and TLR2-TLR6 dimerization. These results reveal the mechanism that underlies Tomaralimab binding to TLR2 and should help to design structure-based mimics or bispecific antibodies that can be used to inhibit both lipopeptide-binding and TLR2 dimerization."

IO biomarker • Journal • Immunology • Inflammation • TLR2

Bioasis and Neuramedy Enter into Research Collaboration and License Agreement (GlobeNewswire) - "BIOASIS TECHNOLOGIES INC...announced today that it has entered into a research collaboration and license agreement with Neuramedy Co Ltd ('Neuramedy') of Seoul, Korea....Under the terms of the agreement, Neuramedy has obtained worldwide rights to research, develop and commercialize an xB3TM version of its antibody, Tomaralimab, directed at the Toll-like receptor 2. Tomaralimab is currently in development for the treatment of Parkinson’s disease and Multiple System Atrophy."

Licensing / partnership • CNS Disorders • Parkinson's Disease