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Nyanguile Origène

Professeur-e HES Ordinaire, Responsable du groupe de recherche Peptide and Protein Technologies

Main skills

Antibody Drug Conjugates (ADCs)

Professeur-e HES Ordinaire, Responsable du groupe de recherche Peptide and Protein Technologies

Phone:+41 58 606 86 51

Desktop: ENP.19.N504

HES-SO Valais-Wallis - Haute Ecole d'Ingénierie
Rue de l'Industrie 23, 1950 Sion, CH

Faculty
Chimie et sciences de la vie

Main Degree Programme
Ingénierie des Sciences du vivant

Institute
Institut Sciences du vivant

BSc HES-SO en Ingénierie des sciences du vivant - HES-SO Valais-Wallis - Haute Ecole d'Ingénierie

Ongoing

Discovery and pre-clinical development of inhalable RSV peptides antivirals

Role: Main Applicant

Description du projet:

Respiratory Syncytial Virus (RSV) is a significant medical threat causing 33 million infections, 3.6 million hospitalizations, and 100’000 annual deaths each year worldwide. Furthermore, RSV infections accounts for 31% of global pneumonia cases, raising particular concern among young children with congenital heart diseases, chronic lung diseases and conditions affecting muscles and nerves. The costs associated with RSV infections, estimated at 4.82 billion euros in 2017, impose a considerable economic burden.
Although the recent launch of the antibody Nirsevimab will most likely help reduce RSV infections, and other vaccines appear to be close to approval, these biologics are all preventive treatment only, and there is no therapy available to treat infected patients. Since RSV infection begins and replicates in the respiratory tract (RT), targeting the RT at the replication sites appears to be an interesting strategy to block infection. In this perspective, patented anti-RSV peptides have been developed at the HES-SO Valais. These peptides block the fusion and the replication of the virus.

In this project, we wish to develop potent antiviral RSV peptide, with the aim to investigate them in tolerance, pharmacokinetics and feasibility studies. To enhance mucus permeation and/or deposit in the lungs, the use nanocarriers will be investigated. The overall objective will be to have selected an intranasal or pulmonary administration.

Research team within HES-SO: Nyanguile Origène , Fung Cédric , Roh Logan , Walker Anne

Partenaires académiques: Galloux Marie, INRAE; Heuzé Vourc'h Nathalie, Université de Tours; Tapparel Caroline, Université de Genève; Milosevic Irena, Hepia

Durée du projet: 01.04.2025

State: Ongoing

Development of methods for the site selective conjugation of payloads to antibody fragments

Role: Main Applicant

2026

Double-stapled peptide scan yields potent fusion inhibitors of respiratory syncytial cvrus

Scientific paper ArODES

Nadège Pidoux, Logan Roh, Nancy Nicolet, Roger Marti, Adrien Le Rouzic, Clémentine Prompt, Jenna Fix, Stéphane Duquerroy, Félix Rey, Marie-Anne Rameix-Welti, Mathilde Keck, Peggy Barbe, Dominique Garcin, Geneviève Mottet-Osman, Thibaut Larcher, Marie Galloux, Origène Nyanguile

Journal of Medicinal Chemistry, 2026, 69, 11, 12910-12924

Link to the publication

2023

Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release

Scientific paper ArODES

Viktoriia Postupalenko, Léo Marx, Mathilde Pantin, David Viertl, Nadège Gsponer, Gaëlle Giudice, Natalia Gasilova, Margret Schotellius, Frédéric Lévy, Patrick Garrouste, Jean-Manuel Segura, Origène Nyanguile

Chemical Science, 15, 2024, 4, 1324-1337

Link to the publication

2022

Template directed synthesis of antibody Fc conjugates with concomitant ligand release

Scientific paper ArODES

Viktoriia Postupalenko, Léo Marx, David Viertl, Nadège Gsponer, Natalia Gasilova, Thibaut Denoel, Niklaus Schaefer, John O. Prior, Gerrit Hagens, Frédéric Lévy, Patrick Garrouste, Jean-Manuel Segura, Origène Nyanguile

Chemical Science, 2022, vol. 13, pp. 3965-3976

Link to the publication

2021

Peptide Technologies at Energypolis

Scientific paper ArODES

Marc Mathieu, Origène Nyanguile

CHIMIA, 2021, vol. 75, no. 6, pp.539-542

Link to the publication

Peptide Technologies at Energypolis

Scientific paper

Mathieu Marc, Nyanguile Origène

CHIMIA, 2021 , vol. 75, no 6

2020

Targeting the Respiratory Syncytial Virus N 0-P Complex with Constrained α-Helical Peptides in Cells and Mice

Scientific paper

Nyanguile Origène

Antimicrob Agents Chemother, 2020 , vol. 64, no 10, pp. 717-20

Link to the publication

2019

Peptide antiviral strategies as an alternative to treat lower respiratory viral infections

Scientific paper ArODES

Origène Nyanguile

Frontiers in Immunology, 2019, vol. 10, article no. 1366

Link to the publication

2017

A short double-stapled peptide inhibits respiratory syncytial virus entry and spreading

Scientific paper ArODES

Vanessa Gaillard, Marie Galloux, Dominique Garcin, Jean-François Eléouët, Ronan Le Goffic, Thibaut Larcher, Marie-Anne Rameix-Welti, Abdelhak Boukadiri, Julien Héritier, Jean-Manuel Segura, Elodie Baechler, Miriam Arrell, Geneviève Mottet-Osman, Origène Nyanguile

Antimicrobial Agents and Chemotherapy, 2017, vol. 61, no. 4, article no. e02241-16

Link to the publication

2014

Discovery and early development of TMC647055, a non-nucleoside inhibitor of the hepatitis C virus NS5B polymerase

Scientific paper

Nyanguile Origène

J Med Chem, 2014 , vol. 57, no 5, pp. 1880-92

Link to the publication

2013

Discovery and early development of TMC647055, a non-nucleoside inhibitor of the hepatitis C virus NS5B polymerase

Scientific paper ArODES

Maxwell D. Cummings, Tse-I Lin, Lili Hu, Abdellah Tahri, David McGowan, Katie Amssoms, Stefaan Last, Benoit Devogelaere, Marie-Claude Rouan, Leen Vijgen, Jan Martin Berke, Pascale Dehertogh, Els Fransen, Erna Cleiren, Liesbet van der Helm, Gregory Fanning, Origène Nyanguile, Kenny Simmen, Pieter Van Remoortere, Pierre Raboisson, Sandrine Vendeville

Journal of Medicinal Chemistry, 2013, vol. 57, no. 5, pp. 1880-1892

Link to the publication

2012

Structure-based macrocyclization yields hepatitis C virus NS5B inhibitors with improved binding affinities and pharmacokinetic properties

Scientific paper ArODES

M. D. Cummings, T. Lin, L. Hu, A. Tahri, D. McGowan, K. Amssoms, S. Last, B. Devogelaere, M.-C. Rouan, L. Vijgen, J. M. Berke, P. Dehertogh, E. Fransen, E. Cleiren, L. van der Helm, G. Fanning, K. Van Emelen, Origène Nyanguile, K. Simmen, P. Raboisson, S. Vendeville

Angewandte Chemie International Edition, 2012, vol. 51, no. 19, pp. 4637-4640

Link to the publication

Finger loop inhibitors of the HCV NS5b polymerase. Part II. Optimization of tetracyclic indole-based macrocycle leading to the discovery of TMC647055

Scientific paper

Nyanguile Origène

Bioorg Med Chem Lett, 2012 , vol. 22, no 12, pp. 4437-43

Link to the publication

Finger-loop inhibitors of the HCV NS5b polymerase. Part 1: Discovery and optimization of novel 1,6- and 2,6-macrocyclic indole series

Scientific paper

Nyanguile Origène

Bioorg Med Chem Lett, 2012 , vol. 22, no 13, pp. 4431-6

Link to the publication

TMC647055, a potent nonnucleoside hepatitis C virus NS5B polymerase inhibitor with cross-genotypic coverage

Scientific paper

Nyanguile Origène

Antimicrob Agents Chemother, 2012 , vol. 56, no 9, pp. 4676-84

2010

1a/1b subtype profiling of nonnucleoside polymerase inhibitors of hepatitis C virus

Scientific paper

Nyanguile Origène

J Virol, 2010 , vol. 84, no 6, pp. 2923-34

Link to the publication

2009

1,5-Benzodiazepine inhibitors of HCV NS5B polymerase

Scientific paper

Nyanguile Origène

Bioorg Med Chem Lett, 2009 , vol. 19, no 9, pp. 2492-6

Link to the publication

Structure-based design of a benzodiazepine scaffold yields a potent allosteric inhibitor of hepatitis C NS5B RNA polymerase

Scientific paper

Nyanguile Origène

J Med Chem ., 2009 , vol. 52(14):4099-102, no 14, pp. 4099-102

1,5-Benzodiazepine inhibitors of HCV NS5B polymerase

Scientific paper

Nyanguile Origène

Bioorg Med Chem Lett, 2009 , vol. 19, no 9, pp. 2492-6

Link to the publication

2008

Antiviral suppression vs restoration of RIG-I signaling by hepatitis C protease and polymerase inhibitors

Scientific paper

Nyanguile Origène

Gastroenterology, 2008 , vol. 135, no 5, pp. 1710-1718

Link to the publication

1,5-benzodiazepines, a novel class of hepatitis C virus polymerase nonnucleoside inhibitors

Scientific paper

Nyanguile Origène

Antimicrob Agents Chemother ., 2008 , vol. 52, no 12, pp. 4420-31

Link to the publication

2006

Adenoviral gene vector tethering to nanoparticle surfaces results in receptor-independent cell entry and increased transgene expression

Scientific paper

Nyanguile Origène

Mol Ther, 2006 , vol. 14, no 3, pp. 382-91

Link to the publication

Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents

Scientific paper

Nyanguile Origène

Proc Natl Acad Sci U S A, 2006 , vol. 103, no 1, pp. 159-64

Link to the publication

2003

Synthesis of adenoviral targeting molecules by intein-mediated protein ligation

Scientific paper

Nyanguile Origène

Gene Ther, 2003 , vol. 10, no 16, pp. 1362-9

2001

A versatile framework for the design of ligand-dependent, transgene-specific transcription factors

Scientific paper

Nyanguile Origène

Mol Ther, 2001 , vol. 3, no 2, pp. 262-73

Link to the publication

Template-directed interference footprinting of protein-phosphate contacts in DNA

Scientific paper

Nyanguile Origène

Org Lett, 2001 , vol. 3, no 1, pp. 71-4

Link to the publication

1997

A nonnatural transcriptional coactivator

Scientific paper

Nyanguile Origène

Proc Natl Acad Sci U S A, 1997 , vol. 94, no 25, pp. 1340-26

Link to the publication

Induced alpha helix in the VP16 activation domain upon binding to a human TAF

Scientific paper

Nyanguile Origène

Science, 1997 , vol. 277, no 5330, pp. 1310-3

Link to the publication

2024

A novel site selective antibody conjugation technology ID: 1080 TOPIC: Emerging peptide-based technologies

Conference

Nyanguile Origène

37th European Peptide Symposium, 25.08.2024 - 29.08.2025, Florence, Italy

Link to the conference

Summary:

Methods to conjugate payloads site-specifically to monoclonal antibodies (mAbs) have gained a
considerable interest particularly in the field of antibody drug conjugates (ADCs), because of the
challenges encountered with heterogenous conjugates in the clinics. Methods that do not require
genetic engineering such as disulfide rebridging, transglutaminase and glycan modifications have
been successfully developed [1], but they all require chemical modification of the mAbs prior to the
conjugation step. Recently, template directed conjugation technologies have emerged as a means to
address this issue. In these reports, a ligand is used to bring a chemical reactive site in proximity to a
mAb targeted lysine[2]. However, these technologies require several chemical steps to obtain the
conjugates and it remains challenging to conjugate the payload site selectively at a single lysine
residue.
Here, we will present a template directed method that enables to conjugate payloads site selectively
to the mAb Fc domain with the concomitant release of the ligand [3]. Our method is based on the use
of a Fc-III ligand, a 13-mer peptide ligand that binds into the hinge region located in the IgG Fc
domain. A Fc-III residue was engineered with a chemically cleavable carbonate reactive site, a
reactivity modulator and the payload. Upon binding to IgG Fc, the antibody lysine is poised to attack
the carbonate site of the Fc-III reactive conjugate, and the Fc-III peptide is released simultaneously
with the formation of a carbamate bond between the payload and the mAb. Using a semicombinatorial
approach and molecular modeling, we have optimized the position and length of the
Fc-III substituent to which the carbonate chemically cleavable site is attached. Among all variants
that were tested, L6Orn-carbonate appeared to be the best candidate yielding a degree and yield of
conjugation of almost 2 and 100%, for a broad array of payloads. We will show in vivo proof of
concept using radiolabeled [64Cu]Cu-atezolizumab.

2023

A Highly Selective Antibody Modification Technology

Conference

Nyanguile Origène

Biologics UK 2023, 30.03.2023 - 31.03.2023, London, UK

Link to the conference

2022

AbYlinkTM: A site-selective labeling method for preclinical imaging of therapeutic antibodies

Conference

Nyanguile Origène

AACR annual meeting 2021, 10.04.2022 - 15.01.2021, Virtual meeting

Link to the conference

Summary:

Clinical development of therapeutic antibodies relies on robust and thorough preclinical evaluation of multiple pharmacodynamic and pharmacokinetic parameters of antibody candidates. While current methods are available for in vitro characterization of antibodies, in vivo determination of tissue distribution, tumor accumulation and retention and potential off-target effects cannot be performed non-invasively in vivo over a prolonged period of time.
Here, we used AbYlinkTM, a novel site-selective labeling method of native antibodies, enabling the single-step covalent conjugation of a radionuclide chelator to the Fc domain of any IgG antibody isotype. Given the selectivity of this reaction for the Fc region of the immunoglobulin, labeling of the antibody at this location should not compromise binding to the antigen. Chelators that are covalently attached to the antibody allows for the labeling with radioisotopes such as 68Ga, 177Lu, 111In and 89Zr, and for the sensitive and quantitative molecular in vivo measurement by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT). AbYlinkTM also permits the conjugation of fluorescent dyes to antibodies with the aim to measure antibody pharmacodynamic parameters by intravital microscopy. In this work, we have validated the technology by labeling several antibodies and ADCs with different payloads. Importantly, antibodies conjugated with AbYlinkTM retained the same affinity to the antigen as the original, unconjugated antibodies, contrary to the randomly labelled antibodies. We will also present data on the specific radiolabeling of commercially available trastuzumab with 111Indium and the SPECT images obtained after injection of mice bearing HER2-positive tumors with 111In-trastuzumab. The present data suggest that AbYlinkTM can be used to support preclinical drug discovery tools to assist in the selection of therapeutic antibody candidates and/or for pharmacodynamic assessment of commercial antibodies. Furthermore, the specificity of the chemical conjugation suggests that AbYlinkTM can help to control the chelator distribution on the antibody drug conjugates.

2016

Discovery of short stapled peptides, inhibitors of RSV fusion

Conference

Nyanguile Origène

RSV16 10th International conference respiratory syncytial virus symposium, 28.09.2016 - 01.10.2016, Bariloche, Patagonia - Argentina

PEOPLE@HES-SO
Directory and Skills inventory

Nyanguile Origène

Professeur-e HES Ordinaire, Responsable du groupe de recherche Peptide and Protein Technologies

Main skills

Inhalable Antiviral Peptides

Antibody Drug Conjugates (ADCs)

Drug Discovery

Biochemistry

Bioconjugation

Peptide Chemistry

Professeur-e HES Ordinaire, Responsable du groupe de recherche Peptide and Protein Technologies

PEOPLE@HES-SO Directory and Skills inventory

Nyanguile Origène

Professeur-e HES Ordinaire, Responsable du groupe de recherche Peptide and Protein Technologies

Main skills

Inhalable Antiviral Peptides

Antibody Drug Conjugates (ADCs)

Drug Discovery

Biochemistry

Bioconjugation

Peptide Chemistry

Professeur-e HES Ordinaire, Responsable du groupe de recherche Peptide and Protein Technologies

PEOPLE@HES-SO
Directory and Skills inventory