Preclinical type 1 diabetes (T1D) research has made important advances in recent years, but less progress has been made in translating findings from in vitro and animal models into effective clinical interventions. INNODIA aims to achieve a breakthrough in the way in which we study T1D to enable us to move closer towards prevention and cure of T1D. To this end, INNODIA joins together the leading European experts from the fields of basic and clinical T1D research, four leading pharmaceutical companies with strong expertise in the discovery and development of diabetes medicines and the two leading public organizations involved in T1D research into one comprehensive collaborative consortium. The clinicians in INNODIA oversee T1D registries and have access to large populations of children and adults with T1D and family members at increased risk of developing the disease. The basic science researchers are experts in beta-cell pathophysiology, immunology, biomarker discovery, bioinformatics, systems biology and clinical trial design. INNODIA will accelerate understanding of T1D through coordinated studies of unique clinical samples and translation-oriented preclinical models. This should deliver novel biomarkers and interventions for testing in appropriately designed trials, to be developed in active collaboration with regulators and patients. INNODIA provides access to unique historical biorepositories and will create the Clinical Sample Network, a clinical EU infrastructure to recruit T1D subjects at diagnosis and at-risk relatives. These individuals will be deep-phenotyped and will provide biosamples, allowing the establishment of a ‘living biobank’ of subjects consented for recall. They will be characterized using standardized clinical, genetic and metabolic phenotyping procedures, including prospective, longitudinal sample collection to facilitate novel biomarker discovery. Diverse biological samples (blood, plasma, serum, urine, stools, etc.) will be collected at

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. INNODIA 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.

Univercell Biosolutions (UB) is a pioneering biotech company providing unique human cell models to accelerate and secure pharmaceutical products. UB is generating 1 M€ turnover in 2015 selling its first generation of human beta cell lines to 10 world pharma industry leaders. Pharmas rentability is decreasing facing to high regulatory pressure and low clinical predictability on human. The rate of clinical drug failure is about 90% and cost for marketed a new drug reach up to 1billion dollars. Early clinical predictability is a strategic issue for industrials. Jan Tornell an AstraZeneca division leader says: “The big think is that when we get into patients, we want no surprise”. Cells from human tissues samples are scarce and not accessible for Pharmas applications. Thus, Industrials developed substitute from animal with poor clinical predictability. Recently, Stem cell technologies has open new hope in providing large quantity of human cells but is still faced with major bottlenecks: lack of cell maturity (clinical predictability) and low cell population homogeneity (reproducibility) which prevents large adoption by industrials. UB has developed a portfolio of cutting edge technologies to overcome these bottlenecks. The first outcome of BETASCREEN is a disruptive pancreatic beta cell line for anti-diabetes research, with ultimate objective of replication to other cell types. The solution targets pharmaceutical, biotech, and academia. Within BETASCREEN, UB will define best commercialization strategy in coherence with market’s targeted segments and identify industrial partners for large-scale production (Phase 2) and commercialization. BETASCREEN will improve the predictive value of screening by decreasing the drug attrition rate up to 10%. Resulting cost saving for industrials could reach 100 million dollars per innovative new drug development. This will open exceptional commercial avenues for UB with revenues estimated at 15 M€ in 2021 and 110 jobs creation in Europe

The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 1 and 2a trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement. To develop the world’s first rigorously proven, effective treatment of DDD, RESPINE aims to assess, via a multicentre, randomized, controlled, phase 2b clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly (within 3 months) and sustainably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised. The transfer to the clinic will be prepared at a cost below 10k€ thanks to the strategy of production of allogenic cells, automation & EU standardisation. At the end of the RESPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs.