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Cellular BIOtechnology for prognosis and monitoring in renal TRANSplantation

Periodic Reporting for period 3 - TRANSBIO (Cellular BIOtechnology for prognosis and monitoring in renal TRANSplantation)

Reporting period: 2018-11-01 to 2019-06-30

End-stage kidney disease is the last stage of a chronic kidney disease, which if not addressed leads to premature death and, although it can be addressed by dialysis, kidney transplantation is the preferred treatment due to better survival rates, improved quality of life & cost efficiency. The most important challenge is to achieve the long-term survival of the transplanted organ. Graft survival depends on the ability of the recipient of not rejecting the foreign organ. Rejection is a naturally occurring process triggered by a biological response of the immune system and nowadays it is prevented by immunosuppressive therapies. Although these therapies have represented a huge step forward in organ transplantation, their use still entails important problems:
Suppressing the immune system implies severe side effects like infections, cancer and other severe pathologies.
Even under immunosuppressive therapies, about 50% of transplanted kidneys are lost during the first 10 years and there are several reasons but the most important is related to rejection mechanisms.
Therefore, the major challenges in kidney transplantation deal with avoiding the side effects associated with immunosuppressant drugs and avoiding rejection. In TRANSBIO we aim at bringing to the market a non-invasive blood test that will provide an important piece of information to personalize and monitor the adequacy of immunosuppressive therapy for each patient.
The IVD test has been named Inmunobiogram®. It is a combination of a biotechnological assay and software for data analysis. Specifically, to run the bioassay a 10mL sample of blood from the patient is needed. It is set up a PBMCs 3D culture in semi-solid matrix submitted to specific stimulation which replicates antigen presentation. Inmunobiogram® mimics immune response in which PBMC replicate and expand (C+), and this response is compared with no stimulation (C-) and with stimulation in presence of immunosuppressants (C+ with IMs). Data is analyzed with a software and output is an evaluation of the sensitivity degree of patient´s circulating immune cells to a panel of immunosuppressant most recommended in clinical guidelines and most used in the clinical setting. The bioassay uses well known immunosuppressants, but it can be adapted for testing new compounds against marketed ones.
Considering that worldwide, the number of people receiving renal transplantation annually is estimated at about 80000 people, growing by approx 6% annually and representing a prevalence of about 700 patients per million population, or what is the same about 5 million people living with a transplanted kidney.
In this project, performed in collaboration with renowned international experts in Nephrology, our goal was to evaluate the analytical robustness and clinical utility of our technology through clinical program comprising two studies. This will enable us to get the regulatory approval (CE marking) for commercialization and bring our product to the healthcare market. The specific objectives are as follows:
1. To optimize the prototype test kit. A price reduction of 25-30% can be achieved by reducing the number of cellular/molecular markers involved, to those most relevant. This prototype optimization was to be done by a pilot clinical study
2. To perform a multicenter validation study in collaboration with some of the most relevant Nephrology Transplantation Units in EU. This clinical study will be aimed at validating the actual analytical robustness of the test and correlation with clinical outcomes, for its approval by the regulatory bodies.
3. To develop a bioinformatics platform as a software tool, based on the results of the clinical validation study. The software will analyze the test results and will deliver the report with the conclusions of the test.
1) We have successfully optimized the test KIT as planned during BH-Pilot Clinical Study which included 70 patients from Puerta de Hierro and La Paz University Hospitals (Madrid).
- We selected clinical biomarkers combined with Biohope’s immunoassay, as the final tool, from the initial multi-screening panel identified. We have optimized the immunoassay to improve its capabilities to describe sensitivity grades patterns to a panel of immunosuppressants.
- Results from Pilot study indicated that our optimized KIT could personalize immunosuppressant treatment much better than current standards.
2) New patent submissions were delivered because of this task. A European Patent has been granted in May 2019 with the optimized KIT
3) We have successfully finished an International (EU+US) Multicenter Validation Clinical Study (TRANSBIO Clinical Study), which included 9 renowned Units of Renal Transplantation, which has confirmed the clinical utility and robustness of our test KIT (Immunobiogram) in renal transplantation.
4) We have created a full software integrated solution for the management of Immunobiogram.
5) We have created a full Quality System in the company and we are under ISO13485 certification process.
6) We are about to submit a CE marking certification (declaration of conformity) in 1Q2020, which will allow us to start sells next year as declared in our business plan
7) We have extensively conducted dissemination and communication activities. We have more online and offline presence. We attended and presented our results in medical-scientific community congresses and we attended fairs. About Scientific Congresses, we have presented TRANSBIO project and data in the most relevant Renal Transplantation Congresses of the world with very good feed-back and one honor mention received. We are also having more contact with public health agencies and patient/professional associations. Finally, we are attending international investor forums.
At Biohope, we realized the major limitations of current approaches in management of kidney transplantation, were dealing with the complexity of the immune response process. This research resulted the first pharmacodynamic immune assay capable of assist physician in the selection of the best treatment possible to prevent rejection. Immunobiogram (IMBG), the major deliverable of TRANSBIO project, is a immunoassay that aims to support physicians to check and monitor the sensitivity/resistance immune profile in vitro of a patient with renal transplantation (RT) to a battery of immunosuppressive drugs normally used in clinical practice to avoid graft rejection. IMBG can support clinicians to take informed decisions to adequate the immunosuppressive treatment in patients with RT, contributing to decrease the risk of graft rejection and the appearance of IS adverse events.
As it is the first Precision Medicine tool capable of a potency evaluation of a panel of immunosuppresants, our technology will overcome the current limitations of the state-of-the-art solutions, with no competitors offering a similar approach. Thanks to these unique features, we envisage our test has the potential to become the next revolution in renal replacement therapy.
The socio-economic impact resides in a gross margin of 3.5 million approx. in 2022. Also, a 36,95% ROE since year 2021 considering other projects after TRANSBIO will come.
TRANSBIO has contributed to job creation: the employees’ number has been increased. Before TRANSBIO project, there was 3 employees. During TRANSBIO project the employees has been increased up to 19.