Delving into the Latest Updates on MIS-416 with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

Target

Mechanism

NOD2 antagonists(Nucleotide-binding oligomerization domain-containing protein 2 antagonists), TLR9 antagonists(Toll like receptor 9 antagonists)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases+ [2]

Active Indication-

Inactive Indication

Infectious DiseasesMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Primary Progressive+ [3]

Originator Organization

Amplia Therapeutics Ltd.

Active Organization-

Inactive Organization

Amplia Therapeutics Ltd.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Phase I Clinical Study on the Long-term Combination Therapy of CHP-NY-ESO-1 Cancer Vaccine and MIS416 for the Treatment of Patients with NY-ESO-1-expressing Refractory Solid tumor. - Phase I Clinical Study on the Long-term Combination Therapy of CHP-NY-ESO-1 Cancer Vaccine and MIS416 for the Treatment of Patients with NY-ESO-1-expressing Refractory Solid Tumor.

Start Date01 May 2012

Sponsor / Collaborator-

100 Clinical Results associated with MIS-416

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100 Translational Medicine associated with MIS-416

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100 Patents (Medical) associated with MIS-416

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14

Literatures (Medical) associated with MIS-416

01 Dec 2020·Acta Neuropathologica CommunicationsQ2 · MEDICINE

Innate signaling within the central nervous system recruits protective neutrophils

Q2 · MEDICINE

ArticleOA

Author: Owens, Trevor ; Kavan, Stephanie ; Hansen, Christian Rønn ; Thomassen, Mads ; Webster, Gill A ; Khorooshi, Reza ; Kruse, Torben ; Burton, Mark ; Dieu, Ruthe Storgaard ; Wais, Vian ; Marczynska, Joanna

AbstractThere is great interest in understanding how the central nervous system (CNS) communicates with the immune system for recruitment of protective responses. Infiltrating phagocytic monocytes and granulocytes are implicated in neuroinflammation in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). To investigate how CNS endogenous signals can be harnessed to promote anti-inflammatory programs, we have used a particulate Toll-like receptor 9 and nucleotide-oligomerization domain 2 bispecific innate ligand (MIS416), to address whether its phagocytosis within the CNS recruits protective myeloid cells. We find that MIS416 injected intrathecally into the cerebrospinal fluid via the cisterna magna induced a local chemokine response that recruited blood-derived monocytes and neutrophils to the CNS. These cells phagocytosed MIS416. The increase in EAE severity normally seen from time of onset did not occur in mice receiving MIS416. This suppression of disease symptoms was dependent on expression of the type I interferon receptor (IFNAR). Transfer of intrathecal MIS416-induced neutrophils suppressed EAE in recipient mice, while monocytes did not transfer protection. MIS416-induced neutrophils showed increased IL-10 expression that was IFNAR1-driven. 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.

01 Apr 2020·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Kageyama, Shinichi ; Mizuno, Toshiro ; Ishihara, Mikiya ; Harada, Naozumi ; Ikeda, Hiroaki ; Shiku, Hiroshi ; Shiraishi, Taizo ; Sato, Eiichi ; Kanda, Hideki ; Katayama, Naoyuki ; Sasaki, Takeshi ; Muraoka, Daisuke ; Hori, Yasuhide ; Miyahara, Yoshihiro ; Tono, Yasutaka ; Sugimura, Yoshiki ; Webster, Gill A ; Soga, Norihito ; Uchida, Katsunori

AbstractCholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (μg/μg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4–5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. 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.

01 Sep 2019·Journal of Allergy and Clinical ImmunologyQ1 · MEDICINE

Toll-like receptor 9–dependent interferon production prevents group 2 innate lymphoid cell–driven airway hyperreactivity

Q1 · MEDICINE

Article

Author: Lai, Alan Chuan-Ying ; Chi, Po-Yu ; Webster, Gill ; Thio, Christina Li-Ping ; Chang, Ya-Jen

BACKGROUNDGroup 2 innate lymphoid cells (ILC2s) are important mediators of allergic asthma. Bacterial components, such as unmethylated CpG DNA, a Toll-like receptor (TLR) 9 agonist, are known to possess beneficial immunomodulatory effects in patients with T cell-mediated chronic asthma. However, their roles in regulating ILC2s remain unclear.OBJECTIVEWe sought to determine the role of TLR9 activation in regulating ILC2 function and to evaluate the therapeutic utility of an immunomodulatory microparticle containing natural TLR9 ligand (MIS416).METHODSWe evaluated the immunomodulatory effects of CpG A in IL-33-induced airway hyperreactivity (AHR) and airway inflammation. The roles of interferons were examined in vivo and in vitro by using signal transducer and activator of transcription 1 (Stat1)^-/- mice and neutralizing antibodies against IFN-γ and IFN-α/β receptor subunit 1, and their cellular sources were identified. The therapeutic utility of MIS416 was investigated in the Alternaria alternata model of allergic asthma and in humanized NSG mice.RESULTSWe show that TLR9 activation by CpG A suppresses IL-33-mediated AHR and airway inflammation through inhibition of ILC2s. Activation of TLR9 leads to production of IFN-α, which drives IFN-γ production by natural killer cells. Importantly, IFN-γ is essential for TLR9-driven suppression, and IFN-α cannot compensate for impaired IFN-γ signaling. We further show that IFN-γ directly inhibits ILC2 function through a STAT1-dependent mechanism. Finally, we demonstrate the therapeutic potential of MIS416 in A alternata-induced airway inflammation and validated these findings in human subjects.CONCLUSIONTLR9 activation alleviates ILC2-driven AHR and airway inflammation through direct suppression of cell function. Microparticle-based delivery of TLR9 ligands might serve as a therapeutic strategy for asthma treatment.

100 Deals associated with MIS-416

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis, Secondary Progressive	Phase 2	NZ	Amplia Therapeutics Ltd.	01 Oct 2014
Multiple Sclerosis, Secondary Progressive	Phase 2	AU	Amplia Therapeutics Ltd.	01 Oct 2014
Multiple Sclerosis, Chronic Progressive	Phase 2	NZ	Amplia Therapeutics Ltd.	01 Aug 2010
Multiple Sclerosis, Primary Progressive	Phase 2	NZ	Amplia Therapeutics Ltd.	01 Aug 2010
Infectious Diseases	Phase 2	NZ	Amplia Therapeutics Ltd.	-
Neoplasms	Phase 2	NZ	Amplia Therapeutics Ltd.	-
Solid tumor	Phase 2	JP	Amplia Therapeutics Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01191996 (Phase 2B trial for the treatment of secondary progressive multiple sclerosis, AAN2017)	Phase 2	Multiple Sclerosis, Secondary Progressive EPO \| VEGF \| HGF ... View more	15	MIS416 500 mg	lwvnyfanqo(aqbtyjjumq) = liohjfkeut jgbboxsscb (cnaxpiyxhc ) View more	Positive	18 Apr 2017
NCT01191996 (Pubmed)	Phase 2	Multiple Sclerosis, Chronic Progressive	34	MIS416	(mdzomorsww) = mnhnhmodpv manndpgote (gmcdcxboff ) View more	-	01 Sep 2015