Delving into the Latest Updates on ASP-7373 with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

組換えインフルエンザHAワクチン（H5N1）

Target-

Action

stimulants

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Influenza A virus infection

Originator Organization

Astellas Pharma, Inc.

UMN Pharma, Inc.

Active Organization-

Inactive Organization

UMN Pharma, Inc.

Protein Sciences Corp.

Vaxine Pty Ltd.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Neuraminidase (NA) is a critical enzyme in the life cycle of influenza virus, which is known as a successful paradigm in the design of anti-influenza agents. However, to date there are no classification models for the virtual screening of NA inhibitors. In this work, we built support vector machine and Naïve Bayesian models of NA inhibitors and non-inhibitors, with different ratios of active-to-inactive compounds in the training set and different molecular descriptors. Four models with sensitivity or Matthews correlation coefficients greater than 0.9 were chosen to predict the NA inhibitory activities of 15,600 compounds in our in-house database. We combined the results of four optimal models and selected 60 representative compounds to assess their NA inhibitory profiles in vitro. Nine NA inhibitors were identified, five of which were oseltamivir derivatives with large C-5 substituents exhibiting potent inhibition against H1N1 NA with IC50 values in the range of 12.9-185.0 nM, and against H3N2 NA with IC50 values between 18.9 and 366.1 nM. The other four active compounds belonged to novel scaffolds, with IC50 values ranging 39.5-63.8 μM against H1N1 NA and 44.5-114.1 μM against H3N2 NA. This is the first time that classification models of NA inhibitors and non-inhibitors are built and their prediction results validated experimentally using in vitro assays.

VaccinesQ3 · MEDICINE

Long-Lasting Mucosal and Systemic Immunity against Influenza A Virus Is Significantly Prolonged and Protective by Nasal Whole Influenza Immunization with Mucosal Adjuvant N3 and DNA-Plasmid Expressing Flagellin in Aging In- and Outbred Mice

Q3 · MEDICINE

ArticleOA

Author: Applequist, Steven E ; Devito, Claudia ; Nyström, Sanna ; Hinkula, Jorma ; Bråve, Andreas

Background: Vaccination is commonly used to prevent and control influenza infection in humans. However, improvements in the ease of delivery and strength of immunogenicity could markedly improve herd immunity. The aim of this pre-clinical study is to test the potential improvements to existing intranasal delivery of formalin-inactivated whole Influenza A vaccines (WIV) by formulation with a cationic lipid-based adjuvant (N3). Additionally, we combined WIV and N3 with a DNA-encoded TLR5 agonist secreted flagellin (pFliC(-gly)) as an adjuvant, as this adjuvant has previously been shown to improve the effectiveness of plasmid-encoded DNA antigens. Methods: Outbred and inbred mouse strains were intranasally immunized with unadjuvanted WIV A/H1N1/SI 2006 or WIV that was formulated with N3 alone. Additional groups were immunized with WIV and N3 adjuvant combined with pFliC(-gly). Homo and heterotypic humoral anti-WIV immune responses were assayed from serum and lung by ELISA and hemagglutination inhibition assay. Homo and heterotypic cellular immune responses to WIV and Influenza A NP were also determined. Results: WIV combined with N3 lipid adjuvant the pFliC(-gly) significantly increased homotypic influenza specific serum antibody responses (>200-fold), increased the IgG2 responses, indicating a mixed Th1/Th2-type immunity, and increased the HAI-titer (>100-fold). Enhanced cell-mediated IFNγ secreting influenza directed CD4+ and CD8+ T cell responses (>40-fold) to homotypic and heterosubtypic influenza A virus and peptides. Long-term and protective immunity was obtained. Conclusions: These results indicate that inactivated influenza virus that was formulated with N3 cationic adjuvant significantly enhanced broad systemic and mucosal influenza specific immune responses. These responses were broadened and further increased by incorporating DNA plasmids encoding FliC from S. typhimurum as an adjuvant providing long lasting protection against heterologous Influenza A/H1N1/CA09pdm virus challenge.

100 Deals associated with ASP-7373

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Influenza A virus infection	Phase 2	Japan	UMN Pharma, Inc.	17 Sep 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01612000 (PSC25, CTgov)	Phase 1/2	Influenza, Human	341	rHA adjuvant+PanBlok (PanBlok 15µg in 2% SE)	jyrgktejkz(yrmjqfvuhu) = axpykmmgvh jwyjonazfg (dqsmdoaplz, bflsevvcmc - eugcqxtwry) View more	-	25 Nov 2015
				rHA adjuvant+PanBlok (PanBlok 3.8µg in 2% SE)	jyrgktejkz(yrmjqfvuhu) = rsllmffcuq jwyjonazfg (dqsmdoaplz, zgviqcumer - vuobvqvbiq) View more
NCT01147068 (CTgov)	Phase 1/2	Influenza, Human	392	0.5mL Intramuscular Injection (Placebo)	qddeeqvfid(rqsjpqnzkt) = quqhdexryd wrkivuzcwb (kcuzcjkhqz, ufuippmqzg - xyhfuxvyio) View more	-	26 Nov 2012
				0.5mL Intramuscular Injection (PanBlok 135µg No Adjuvant)	qddeeqvfid(rqsjpqnzkt) = rlpapwkbei wrkivuzcwb (kcuzcjkhqz, yphvtnqjdn - qztegbdmqj) View more