Unipi Team Leader: Prof. Piero Marchetti, Dipartimento di Medicina Clinica e Sperimentale

Towards innovative therapies against type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disorder associated with the destruction of pancreatic islet beta cells, leading to little or no insulin production. The EU-funded INNODIA HARVEST project is undertaken by a large network of experts that aim to prevent or arrest T1D through innovative strategies. The project builds on the strong foundations of the INNODIA consortium, its origin. Partners will perform a series of intervention trials to study the mechanisms of T1D, identify biomarkers and study pathways associated with disease pathobiology. Through a beta-cell focussed and an immune-focussed intervention trial, the team hopes to deliver key knowledge for new combination therapies and to establish discovery pipelines for future T1D therapeutics. The people living with T1D remain at the center of INNODIA HARVEST, driving the implementation of patient-centered results, shaping our clinical trials and making meaningful change in the disease perspective.

Objective

Building on the strong foundations of INNODIA, with its unique, Europe-wide clinical and basic research network for the study of type 1 diabetes (T1D), we propose in INNODIA HARVEST an ambitious program which aims to prevent and arrest T1D via focused objectives targeting consolidation and innovation. First, we will consolidate the INNODIA clinical network as the reference point for conducting studies to prevent or arrest T1D. We will transform our standardized clinical and bioresource platforms into a high-performance clinical trial network, running academic and industry-driven trials alongside small, mechanism-centric, biomarker-rich intervention trials to examine pathobiological pathways to T1D. I

NNODIA HARVEST will conduct two large studies to arrest T1D at its onset, one academia-driven, beta-cell focused (VER-A-T1D, verapamil) and one industry-driven, immune-focused (Iscalimab-study). We will exploit our original INNODIA Master Protocol allowing novel adaptive trial design to introduce combination therapies that build on complementary mechanisms. Second, we will extend our study design strategy by introducing novel biomarkers, both clinical (continuous glucose monitoring) and experimental (microbiome analysis) to deconvolute disease heterogeneity and identify new endpoints to accelerate identification of effective therapeutics. Third, we will use ‘disruptors’ in small mechanistic studies to channel innovation from clinic to basic research through a reverse immunology and reverse beta-cell biology approach. Finally, we will implement new discovery pipelines for future therapeutics, exploiting tools such as iPSC-derived islet-like cells to promote next generation target identification and drug development. As in INNODIA, the voice of people living with T1D and their families will hold a central place in INNODIA HARVEST to drive implementation of new, patient-proximal outcomes, shape our clinical trials, and bring about a meaningful change in disease perspective.

A major objective of INNODIA Harvest is the execution of at least two new phase 2 trials (studying Verapamil (VER-A-T1D) or Iscalimab (CCFZ533X2207)). Considering the expected time to first patient-in as preparations for trial start can only be initiated after the start of the Action and possible fluctuating recruiting rates, due to the intercurrent COVID epidemic, there is a risk that INNODIA HARVEST will not be able to completely finalize the clinical trials, fully analyse the biomarkers collected and publish the results in the initially proposed 24 months duration. To ensure the finalization of the clinical trials and corresponding full execution of the given budget including eligibility of EFPIA in-kind contribution we propose to extend the duration of the Action from 24 to 36 months.

Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN, Belgium

Other participants

• THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE, United Kingdom
• MEDIZINISCHE UNIVERSITAT GRAZ, Austria
• UNIVERSITE LIBRE DE BRUXELLES, Belgium
• KOBENHAVNS UNIVERSITET, Denmark
• REGION HOVEDSTADEN, Denmark
• INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE, France
• HELSINGIN YLIOPISTO, Finland
• OULUN YLIOPISTO, Finland
• TURUN YLIOPISTO, Finland
• HANNOVERSCHE KINDERHEILANSTALT, Germany
• HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH, Germany
• TECHNISCHE UNIVERSITAET DRESDEN, Germany
• UNIVERSITAET ULM, Germany
• UNIVERSITA DEGLI STUDI DI SIENA, Italy
• UNIVERSITA DEGLI STUDI GABRIELE D'ANNUNZIO DI CHIETI-PESCARA, Italy
• UNIVERSITA DI PISA, Italy
• CENTRE HOSPITALIER DE LUXEMBOURG, Luxembourg
• THE UNIVERSITY OF EXETER, United Kingdom
• SLASKI UNIWERSYTET MEDYCZNY W KATOWICACH, Poland
• UNIVERZA V LJUBLJANI, Slovenia
• UNIVERSITE DE LAUSANNE, Switzerland
• STICHTING KATHOLIEKE UNIVERSITEIT, Netherlands
• ACADEMISCH ZIEKENHUIS LEIDEN, Netherlands
• KING'S COLLEGE LONDON, United Kingdom
• LUNDS UNIVERSITET, Sweden
• UNIVERCELL BIOSOLUTIONS SAS, France
• SANOFI-AVENTIS DEUTSCHLAND GMBH, Germany
• NOVO NORDISK A/S, Denmark
• GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD., United Kingdom
• Eli Lilly and Company Limited, United Kingdom
• JDRF INTERNATIONAL, United States
• THE LEONA M. AND HARRY B. HELMSLEY CHARITABLE TRUST, United States
• OSLO UNIVERSITETSSYKEHUS HF, Norway
• THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD, United Kingdom
• CARDIFF UNIVERSITY, United Kingdom
• UNIVERSITA VITA-SALUTE SAN RAFFAELE, Italy
• NOVARTIS PHARMA AG, Switzerland
• IMCYSE SA, Belgium
• OSPEDALE PEDIATRICO BAMBINO GESU, Italy

Start date 1 May 2020

End date 30 April 2023
Project cost € 12 442 444
Project funding € 5 999 055
Unipi quota € 126 250
Call title H2020-JTI-IMI2-2019-19-single-stage
Funding scheme MI2-RIA - Research and Innovation action
Unipi role Partner
Project website: https://www.innodia.eu/