MIS416 / Amplia Therap - LARVOL DELTA

Innate Signaling in the CNS Prevents Demyelination in a Focal EAE Model. (PubMed, Front Neurosci) - "Moreover, intrathecal MIS416 altered the composition of early CNS infiltrates, increasing proportions of myeloid and NK cells and reducing T cells at the lesion site. This study contributes to an increased understanding of how innate immune responses can play a protective role, which in turn may lead to additional therapeutic strategies for the prevention and treatment of demyelinating pathologies."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • CCL2 • CXCL10 • IL10 • TLR9

TLR9-dependent interferon production prevents group 2 innate lymphoid cell-driven airway hyperreactivity. (PubMed, J Allergy Clin Immunol) - "TLR9 activation alleviates ILC2-driven AHR and airway inflammation through direct suppression of cell function. Microparticle-based delivery of TLR9 ligands may serve as a therapeutic strategy for asthma treatment."

Journal • Asthma • Immune Modulation • Immunology • Inflammation • Respiratory Diseases

Bridging Small Molecules to Modified Bacterial Microparticles Using a Disulphide Linkage: MIS416 as a Cargo Delivery System. (PubMed) - PLoS One - "In conclusion, inclusion of a disulfide bond in MIS416-peptide conjugates was associated with efficient release of peptides in the cytoplasm of DCs, an important consideration for MIS416-mediated delivery of degradation-sensitive cargoes. However, treatment of DCs with disulfide-containing conjugates did not significantly alter the presentation of peptide antigens on MHC class I molecules to T-cells, or greatly enhance antigen-associated T-cell proliferation in vitro."

Journal • Biosimilar

Innate Immunotherapeutics wins support for multiple sclerosis treatment (Proactiveinvestors) - "Innate Immunotherapeutics...should trade firmer after revealing results from animal studies which further support its MIS416 therapy as a promising candidate to treat Secondary Progressive Multiple Sclerosis...Innate has also announced a research collaboration with renowned multiple sclerosis specialist Professor Larry Steinman, and his group at Stanford University, to further define the effect of MIS416 therapy on neuroinflammatory and neuroprotective pathways."

Preclinical • Multiple Sclerosis

Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis (clinicaltrials.gov) - P2b; N=93; Completed; Sponsor: Innate Immunotherapeutics; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • CNS Disorders • Multiple Sclerosis

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors. (PubMed, Cancer Immunol Immunother) - "In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step."

Clinical • Journal • P1 data • Anorexia • CNS Disorders • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Psychiatry • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer

Innate signaling within the central nervous system recruits protective neutrophils. (PubMed, Acta Neuropathol Commun) - "In contrast to intrathecal administration, intravenous administration of MIS416 led to monocyte but not neutrophil infiltration to the CNS. We thus identify a CNS-intrinsic and -specific phagocytosis-induced recruitment of anti-inflammatory neutrophils that contribute to CNS homeostasis and may have therapeutic potential."

IO Biomarker • Journal • IFNAR1 • IL10

Differential monocytic response patterns to MIS416 in vitro during progressive multiple sclerosis and the involvement of NF-kB. (ECTRIMS 2019) - "These findings support a central role for NF-kB pathway mutations in regulating monocyte responses to MIS416. Overall, this work indicates that MIS416 therapy has the potential to modulate peripheral immune responses through substantive TF and cytokine induction, which can alter the immune milieu following in vivo treatment."

Preclinical