Australia- and New Zealand-based Innate Immunotherapeutics Limited is working on the clinical development of its lead drug candidate MIS416 aimed at treating patients with secondary progressive multiple sclerosis (SPMS). The therapy is an intravenous formulation of an immunomodulatory microparticle which targets both regulatory and defensive functions of the innate immune system, with a novel target of the myeloid cells (a subset of innate immune cells), which has not been targeted by any therapy currently marketed.
How MIS416 Works
MIS416 is a construct of two naturally occurring, non-immunogenic, cytosolic ligands, TLR-9 and NOD-2 (both proteins responsible for pathogen recognition and activation of the innate immune system), which, when absorbed by cells of the reticulo-endothelial system, activate a series of signal transduction pathways which lead to activation of inflammatory pathways involving macrophages, Natural Killer (NK) and NKT cells, dendritic cells and monocytes.
The therapy, however, has a modulatory effect on these pathways and induces activation of a wide range of tumoricidal pathways like those involving members of the Tumor Necrosis Factor (TNF) family, such as Fas, TRAIL (TNF-Related Apoptosis Inducing Ligand) and TNF-alpha. These pathways correlate with the production of NFkB-dependant inflammatory cytokines which act locally and modulate a range of different immune responses.
These findings were prominent in preclinical mouse models, which led to the company’s Phase 1 and 2 clinical trials with humans.
History of MIS416
Phase 1B and 2A clinical trials (completed in November 2012) observing the dose escalation effects in healthy human hosts and progressive MS patients, were conducted to test the drug’s safety, tolerability and efficacy, and pharmacodynamic and pharmacokinetic properties. Following the early success of MIS416, the company later progressed to a phase 2B clinical trial, a randomized, double-blind, placebo-controlled trial of the efficacy and safety of MIS416 in the treatment of subjects with SPMS. Recruitment closed on March 31 for this trial. A total of 90 study subjects are expected to participate.
This study is being conducted in Australia and New Zealand, and is expected to be completed this summer. It is being conducted in collaboration with INC Research.
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