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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - METAdiag (METAdiag: Diagnose to Cure)

Teaser

Summary

METAFORA develops a disruptive blood-based In Vitro Diagnostic platform called METAdiag, METAdiag monitors cellsâ€™ energetic needs thanks to unique, proprietary biomarkers (Receptor Binding Domains or RBDs), able to quantify nutrient transporters used by cells to feed on glucose, amino acids, vitamins and other essential nutrient transporters at the cellâ€™s surface.
Cutting edge algorithms using Artificial Intelligence to handle big data participate in generating actionable results to physicians for routine clinical practice,
METAglut1 is a first test developed to fill a medical unmet need, i.e.: the easy and early diagnosis of a debilitating but curable neuro-metabolic disease in children, GLUT1 Deficiency Syndrome. METAglut1 testâ€™s positive results have been published in a leading scientific journal, has been CE-marked and is at the basis of a partnering agreement with CERBA Healthcare, a leading Medical Testing Laboratory.
Next steps include:
o A large scale validation study in Europe to secure the reimbursement of the test
o Downsizing of the test as a finger prick blood test
o Dissemination of METAglut1 in Europe big 5 countries (Germany, UK, France, Italy and Spain) and North America via business development effort and market access
o Extension of the test application to newborn screening in the USA
Following the validation and commercial launch of this first test, next applications to come out of the METAdiag platform include a breakthrough test enabling the diagnosis and therapeutic monitoring of cancers, with a market launch contemplated 3 years after the Phase 2 project ends.
METAFORA anticipates cumulative revenues of over â‚¬52M and 75 jobs created 5 years after the commercialization of our first test, and ambitions to become a key player in the IVD market

Work performed

TECHNICAL FEASIBILITY

Objective 1: To strengthen the perception of the value of our test. Key findings: we have been able to finalize a scientific publication on the retrospective study we conducted with leading neuropediatricians. The paper has been accepted for publication by a top-tier journal of neurology, Annals of Neurology, in May 2017; this publication highlight the medical promise of the test, and is first step in the marketing effort of our project.

Objective 2: To outline the plan for clinical validation. Key findings: We will perform a large-scale multicentre clinical validation in the setting of the â€œForfait Innovationâ€, the French fast track for the reimbursement of medical devices or diagnostics. The validation will take place during 12 months, as described in page 9.

Objective 3: To define the scale-up process. Key findings: We will need to scale up our analysis capacity and control measures and increase our bioproduction volume. Besides, we will need to complete the technology transfer to the central METAglut1 laboratory of CERBA Healthcare. There is extended information of the scale-up process in page 9.

Objective 4: To finalize the specifications. Key findings: For METAglut1 test, we have designed 2 separate workflows to optimize our procedure and to fully automate it. Wet Workflow: based on liquid blood sampling and testing. Dry Workflow: involves embedding the blood sample in a blot paper in the hospital instead of submitting 1-5 ml of liquid blood to the central laboratory. For more information please refer to page 10.

Objective 5: To confirm pending regulatory requirements. Key findings: METAdiag has been CE marked already, in February 2017 but we will need to CE mark the dry workflow following a similar process. We have determined that METAglut1 will need to follow a de novo process for the classification by the FDA for premarket approval.
We have described the requirements in page 10.

Objective 6: To prepare a detailed work plan. Key findings: Our project will take 28 months to be completed and will be divided in 6 Work Packages. These are described in page 11.

COMMERCIAL FEASIBILITY

Objective 7: To conduct an in-depth analysis of the IVD testing market. Key findings: We have assessed the particularities for commercialization in our main targeted countries (France, Benelux, UK, Italy, Spain, Germany, USA and Canada). We have confirmed the alignment of our project with current market needs and further studied the existing offerings. Detailed information can be found in page 13.

Objective 8: To prepare a plan to expand our deployment network. Key findings: We will secure alliances and agreements with selected laboratories and partners that provide the adequate commercial, technical, clinical and advocacy capabilities, focusing also on confirming the most suitable plan for market introduction and distribution.
The plan is shown in page 17.

Objective 9: To validate our dissemination strategy. Key findings: Building on our existent relationships with a) KOLs on Glut1 Deficiency Syndrome from clinics, research and academia and b) Patients Associations with which we will increase awareness on GLUT1DS by performing the activities in page 17.

Objective 10: To confirm our Freedom to Operate within our target markets. Key findings: we have performed a patent analysis and we have confirmed our FTO in 90 countries, including our target countries for METAdiag.
Our FTO analysis is shown in page 18.

Objective 11: To study other possibilities regarding IPR. Key findings: Our IP protection plan includes renovating our patent protecting METAglut1 and considering the possibility to protect our dry workflow together with AhlstrÃ¶m. We will also keep technology watch for innovations that might interfere with our test. Our IP protection plan has been described in page 18.

FINANCIAL FEASIBILITY

Objective 12: To assess the total investment required to complete this project. Key findings: The full esti

Final results

The ultimate goal of our project is to accelerate the market uptake of METAdiag, the first-of-its-kind diagnostic platform able to assess and monitor the metabolic status of our cells.
METAdiag platform can detect, quantify, analyse and display results of the abnormalities of cell metabolism and diagnose a number of rare diseases, chronic metabolic and inflammatory diseases as well as forms of cancer.
Our first developed METAdiag test, METAglut1, allows neuro-paediatricians to easily diagnose Glut1 Deficiency Syndrome (GLUT1DS) in children. This debilitating disease is associated to epileptic seizures, movement disorders, learning disabilities and even behavioural difficulties. The neurological damage of GLUT1DS can be irreversible if the disease has not been diagnosed and treated timely. However, early diagnosis and treatment with a ketogenic diet allows affected children to lead a healthy life. Unfortunately, currently 90% of GLUT1DS cases are misdiagnosed due to the heterogeneous and atypical symptoms of the disease and to the lack of a non-invasive, not painful and easy to perform diagnosis test for GLUT1DS.
The functional exploration of the syndrome is complex and requires a hospitalization to perform a lumbar puncture and to test glucose in the cerebrospinal. The procedure is highly invasive and painful (subjects being children), and requires highly skilled health professionals, therefore increasing diagnostic costs. Additionally, the full diagnosis of the syndrome involves the analysis of the SLC2A1 gene (encoding gene for Glut1 transporter), which is lengthy, expensive and often not available in hospitals.
On the contrary, our METAglut1 test is:
* Non-invasive and painless, performed using a blood sample,
* Simple, fast and automated, providing both doctor and patient with a result in 24 hours, very quickly after symptoms onset and a clinical suspicion is raised,
* 100% specific, as it directly quantifies Glut1 transporter expression level.
Moreover, our METAdiag platform can be adapted to test a whole variety of diseases such as cancer and metabolic diseases, in which abnormalities in cell energetics is key. We chose GLUT1DS as the first target for our diagnostic platform due to the high incidence of refractory epilepsies in Europe and the USA (30% resistant to available treatments), over 30 millions of patients with intellectual disabilities and 25% due to genetic disorders, all showing compatible symptoms for misdiagnosed cases of GLUT1DS.
It is estimated that approximately 50 million people worldwide suffer from epilepsy. This syndrome is the 4th most common neurological problem, after migraine, stroke and Alzheimerâ€™s disease. The average incidence in developed countries is estimated at around 50 per 100,000 people per year. It is very important to stress, that approximately 70% of people with epilepsy respond to treatment, leaving out 30% who are treated for epilepsy and may actually suffer from other disorders, including GLUT1DS. In particular, it is possible that up to 2% of all idiopathic generalized epilepsy and 10% of early onset absence epilepsy may be undiagnosed GLUT1 deficiency syndrome.
Our technology is packaged into a unique and reliable proprietary in vitro diagnostics (IVD) platform. METAglut1 is our first quick win test addressing an empty market niche that will be ready for worldwide deployment in 2020. METAglut1 test is meant to save years of diagnostic tests and medical wandering for patients, and thousand euros of costs in these tests, hospitalizations and inappropriate treatments.
The monitoring of normal and altered metabolic functions will provide new knowledge on numerous pathologies, including rare diseases, obesity, diabetes and forms of cancer. It will also enable new tests to be developed to improve the prevention of certain diseases and the maintenance of health through this biological measure. Our collaboration with CERBA HealthCare, a leading European medical testing lab, will con