Final Report Summary - NEXT (Nano Engineering for Cross Tolerance: new approach for bioengineered, vascularised, chimeric islet transplantation in non-immunosuppressed hosts.)
Executive Summary:
NEXT main goal was to provide a breakthrough technological alternative to pancreatic islet transplantation (PIT). Currently, PIT is widely recognised as the treatment of choice for Type 1 Diabetes patients who are no longer responsive to insulin administration or who do not experience symptoms of hypoglycaemia. Thus far, these clinical conditions can be treated only with either whole organ transplantation or PIT. The shortage of organ donors makes PIT a very attractive alternative treatment, where islets isolated from cadaveric donors are infused in the liver portal vein of the recipient through a relatively simple and minimally-invasive procedure. However, it is known that regardless of the immunosuppressant therapy associated to their transplantation, most of the transfused islets lose their viability during the first week of grafting in the portal vein because of the immune response, oxidative stress and lack of vascularisation.
NEXT technology developed a tissue engineering pancreatic pseudo-islets to reverse diabetic conditions. The innovative aspect of this project stemmed from the unique combination of the following construct components:
1. A recombinant immunosuppressant protein, produced by the industrial partner EXPLORA, Italy, that could be release locally at the site of transplantation to protect the islets during the early phase of grafting.
2. A biomimetic biomaterial, developed by the academic partner University of Brighton (UK), able to mimic the natural extracellular matrix of a pancreatic islet and capable of driving the tissue-like assembly of pancreatic cells and vascular endothelial cells in to a tissue engineered pseudo-islet.
3. Two types of microgravity static and portable bioreactors, developed by the industrial partner CELLON (L), enabling the assembling of the biomaterial/cell constructs in suspension and their transportation to the nosocomial unit, respectively.
The expertise offered by the industrial partner AvantiCell Science (United Kingdom) and two centres for organ transplantation, ISMETT (Italy) and University of Geneva European Registry for Pancreatic Islet Transplantation (Switzerland) allowed the validation of all the components and final constructs by advanced in vitro and in vivo methods.
The partners made substantial progress towards the optimisation of the bioengineered pancreatic islets, called biochip, capable to partially revert diabetes in a well-established mouse syngenic model.
Project Context and Objectives:
NEXT main goal was to provide a breakthrough technological alternative to pancreatic islet transplantation (PIT). Currently, PIT is widely recognised as the treatment of choice for Type 1 Diabetes patients who are no longer responsive to insulin administration or who do not experience symptoms of hypoglycaemia. Thus far, these clinical conditions can be treated only with either whole organ transplantation or PIT. The shortage of organ donors makes PIT a very attractive alternative treatment, where islets isolated from cadaveric donors are infused in the liver portal vein of the recipient through a relatively simple and minimally-invasive procedure. However, it is known that regardless of the immunosuppressant therapy associated to their transplantation, most of the transfused islets lose their viability during the first week of grafting in the portal vein because of the immune response, oxidative stress and lack of vascularisation.
NEXT technology developed a tissue engineering pancreatic pseudo-islets to reverse diabetic conditions. The innovative aspect of this project stemmed from the unique combination of the following construct components:
1. A recombinant immunosuppressant protein that could be release locally at the site of transplantation to protect the islets during the early phase of grafting
2. A biomimetic biomaterial capable to mimic the natural extracellular matrix of a pancreatic islet and capable of driving the tissue-like assembly of pancreatic cells and vascular endothelial cells in to a tissue engineered pseudo-islet.
3. Two types of microgravity static and portable bioreactors enabling the assembling of the biomaterial/cell constructs in suspension and their transportation to the nosocomial unit, respectively.
The envisaged final product uniquely combines the properties of:
i) mimicking the extracellular matrix present in the pancreatic islets and encouraging the assembly of the beta cells and endothelial cells into structures similar to natural pancreatic islets.
ii) presenting peptides able to induce localised immunosuppression and hence protection from the host response during the early phases of transplantation.
Project Results:
Figure 1 represents the most promising project foregrounds achieved during project implementation.
Figure 1. NEXT’s innovation pipeline
Most notably, the following S/T results were obtained:
i) ACS developed and validated a new cell-based fibrosis assay that will be marketed by ACS in EU from January 2018, and subsequently in other geographic markets. At time of writing, the new service is expected to generate sales between 20 and 40keuro in 2018 fiscal year. This will be followed during calendar year 2018 by a cell-based fibrosis assay kit built upon the same technology.
ii) EXP developed and validated a modular cloning method that is currently marketed by EXP in EU (www.doulix.com). At time of writing, the new service is expected to generate sales between 10 and 15 keuro in 2017 fiscal year.
iii) EXP has signed a world-wide agreement with Agilent Technology Inc for the joint commercialization of products related to DOULIX in USA. At time of writing, the new service is expected to generate sales in excess of 100 keuro in 2018 fiscal year.
iv) EXP has file an international trademark application (Int.Reg. No.1351473) and obtained the trademark “DOULIX – Your toolkit for synthetic biology” for EU (TM nr. 016125577), and USA (TM nr. 79210558). JP application is currently under review.
v) EXP file and obtained a patent for the expression of human recombinant protein in bacterial host (patent nr. IT-1428672, issued on 24 May 2017, valid through 12 February 2035). At time of writing, the new service is expected to generate sales in excess of 100 keuro in 2018 fiscal year.
vi) UoB developed and validated synthetic biomaterials as substrates for pancreas-on-chip assembly. At time of writing, UoB aims to exploit it either through the filing of a patent or through a confidential manufacturing know-how that will be licensed to a start-up company.
vii) CELLON has been promoting their bioreactors as such or in combination with UoB synthetic biomaterials for the culturing of human pancreatic islets and received positive feedback from beta testers.
viii) CELLON has also achieved a proof of concept of islet transport by vehicle using a battery-driven microgravity rotatory bioreactor.
Potential Impact:
The NEXT project proposes a revolutionary technology for improving survival and efficiency of PITX that could be translated to artificial organ construction. Engineering for self-defence the same target cells and assembling them into a chimeric artificial organ may allow cell transfusion/transplantation or bioartificial graft transplantation in the absence of lifetime immunosuppressant therapy. This strategy would dramatically reduce costs of this treatment; it would allow the treatment of non-complicated diabetes by means of functional transplantation (Pancreatic islet) without requiring solid organ transplantation (kidney) and corresponding immune-suppression treatment. The concept of Bio artificial chimeric organ offers a breakthrough in the field and, if successful, will open a new area which can also be expanded in the generation of xenogeneic artificial organs which could overcome the issue of cadaveric organ shortage. The main expected result is the construction and validation of the bioCHIP as described in section 1.
This high risk-high gain goal is complemented with a robust contingency plan that will concentrate on engineering a bioartificial functionalized pancreatic islet, which will still offer huge advantages in terms of efficacy (by reducing the amount of harvested and transplanted islet) and safety (by avoiding systemic immunosuppression).
The World Health Organisation has estimated that 171 million people were affected by diabetes worldwide in 2000 and predicts that 30 million people will be diagnosed with Type 1 diabetes worldwide by the year 2025 (Diabetes Care 2005, 28, 2130–2135). The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2 % of all deaths. Excess mortality attributable to diabetes accounted for 2–3 % of deaths in the poorest countries and over 8 % in the U.S. Canada, and the Middle East. In people 35–64 years old, 6–27 % of deaths were attributable to diabetes. These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death. Diabetes accounts for at least 10 % of total health care expenditure in many countries. However, routinely reported statistics based on death certification seriously underestimate mortality from diabetes, because individuals with diabetes most often die of secondary cardiovascular and renal complications and not from a cause uniquely related to diabetes, such as ketoacidosis or hypoglycemia.
Direct medical expenditures alone totaled $ 91.8 billion and comprised $ 23.2 billion for diabetes care, $ 24.6 billion for chronic complications attributable to diabetes, and $ 44.1 billion for excess prevalence of general medical conditions. Inpatient days (43.9 %), nursing home care (15.1 %), and office visits (10.9 %) constituted the major expenditure groups by service settings. In addition, 51.8% of direct medical expenditures were incurred by people >65 years old. Attributable indirect expenditures resulting from lost workdays, restricted activity days, mortality, and permanent disability due to diabetes totaled $ 39.8 billion. U.S. health expenditures for the health care components included in the study totaled $ 865 billion, of which $ 160 billion was incurred by people with diabetes. Per capita medical expenditures totaled $ 13,243 for people with diabetes and $ 2,560 for people without diabetes. When adjusting for differences in age, sex, and race/ethnicity between the population with and without diabetes, people with diabetes had medical expenditures that were approximately 2.4 times higher than expenditures that would be incurred by the same group in the absence of diabetes.
Visiongain Ltd predicts that the retail market for diabetes medications will continue to show significant growth for what is an already large market. Actos from Takeda is the leading oral anti-diabetic product and appears set to retain this status. However, it is co-marketed with Eli Lilly which has new products to make available. Lantus from Sanofi-Aventis is the leading insulin product. However, the diabetes market is characterized by high unmet need and treatment issues. At the same time, these issues along with radical changes in the understanding of diabetes, have created an environment rich in opportunity. Among them, the alternative treatment based on pancreatic islet transplantation seems to be considered by the experts to be the most attractive
Currently, the rate of pancreatic organ donation is insufficient to allow even 0.1 % of those that could currently benefit from islet transplant therapy to have this treatment option. Recent improvements in the success rate of islet transplantation have provided critical proof of principle that restoration of functional cell mass in patients with Type 1 diabetes can reverse the disease and allow patients freedom from the burden of daily insulin injections. With the advent of the Edmonton Protocol, standard operating procedures for islet purification and delivery are established, and islet transplant centres around the world have been able to reproduce the success of this protocol. The recently established UK Islet Transplant Consortium has brought together all the major UK islet transplant centres, with a view to advancing European islet transplant success rates to those currently achieved in North America.
The main novelties that characterized the NEXT concept are:
• BT1: Inducing local and transient immunosuppression by coating pancreatic islet with immunosuppressive peptides (ISPs). As preferred embodiment, ISPs are conjugated to lysine dendrimers capable of binding β-cells.
• BT2: Reducing host immunorejection against islet graft by encapsulating donor β-cells islet with polymer matrix congaing recipient endothelial cells. As preferred embodiment, donor β-cells islet is encapsulated in VEGF-containing chitosan nanoparticles, which attract recipient progenitor endothelial cells.
• BT3: Increase artificial islet survival rate by culturing them under microgravity conditions.
We envisage two different exploitation strategies:
i) long-term exploitation strategy for the envisaged NEXT artificial pancreatic islet that is expected to reach the market after project completion and no earlier than 5-7 years;
ii) short-term exploitation strategy for intermediate results achieved during the first 36 months that are expected to reach the market within 1-2 years.
As far as long-term exploitation strategy is concerned, the ultimate objective of the NEXT project is to develop a chimeric artificial pancreatic islet capable to escape recipient’s immune response by virtue of vasculature chimerism and physical immune-shielding. Within this framework the envisaged technology fall under the advanced therapy medicinal product (ATMP) category according to Directive 2001/83/EC as amended by the ATMP Regulation 1394/2007. The envisaged technology represents a high-risk/high-gain breakthrough that targets a multi-million dollar market. In addition, the envisaged NEXT’s technology may be exploited for other solid organ transplantation thus targeting a potential global market for valued at nearly $54 billion in 2010 and projected to grow at an 8.3% compound annual growth rate (CAGR) to reach $92 billion in 2017 [Source: BBc Research]. Within this framework and in perspective of the results obtained in vivo (see WP4), the Consortium proactively sought partnership with VC funds for the creation of a NewCo in EU for the exploitation of results in Europe, USA and JP. At the time of writing, the revenues sharing model for the NewCo foresees:
• opt-in for NEXT’s SMEs partners as shareholders of NewCo. Within this framework, funding SMEs will grant exclusive right for the use of their respective background to the NewCo. Alternatively, SMEs may act as service and product provider to the NewCo under terms to be negotiated.
• Fixed-fee agreement for the non-exclusive right to use UoB’s dendron. Alternatively, UoB may act as raw material provider under terms to be negotiated.
• Fee-for-service and milestone-based royalties for UniGE and ISMETT based on work performed to progress NEXT’s technology up to first-in-human.
As far as short-term exploitation strategy is concerned, Figure 1 represents the most promising project foregrounds achieved during project implementation.
Most notably:
Capitalising on the results so far achieved, the project Steering Committee has identified intermediate products and clear commercial benefits for the industrial partners:
i) AvantiCell has demonstrated the suitability of their tests to measure in a reliable manner the viability of beta cells and pancreatic islets prior to transplantation. The company has also optimised a commercially-viable procedure for the isolation of endothelial cell progenitors from human peripheral blood. Relevant to the prediction of the immune response to tissue engineering constructs, ACS has also developed a predictive in vitro model for fibrosis.
ii) Explora has developed an immunosuppressant recombinant protein that has the potential of being used in clinical applications beyond islet transplantation.
iii) CELLON has proven the efficacy and adaptability of their bioreactor in assembling bioengineered islets as well as in ensuring the survival and functionality of islets upon a clinically-relevant period of time.
List of Websites:
www.thenext-project.eu
NEXT main goal was to provide a breakthrough technological alternative to pancreatic islet transplantation (PIT). Currently, PIT is widely recognised as the treatment of choice for Type 1 Diabetes patients who are no longer responsive to insulin administration or who do not experience symptoms of hypoglycaemia. Thus far, these clinical conditions can be treated only with either whole organ transplantation or PIT. The shortage of organ donors makes PIT a very attractive alternative treatment, where islets isolated from cadaveric donors are infused in the liver portal vein of the recipient through a relatively simple and minimally-invasive procedure. However, it is known that regardless of the immunosuppressant therapy associated to their transplantation, most of the transfused islets lose their viability during the first week of grafting in the portal vein because of the immune response, oxidative stress and lack of vascularisation.
NEXT technology developed a tissue engineering pancreatic pseudo-islets to reverse diabetic conditions. The innovative aspect of this project stemmed from the unique combination of the following construct components:
1. A recombinant immunosuppressant protein, produced by the industrial partner EXPLORA, Italy, that could be release locally at the site of transplantation to protect the islets during the early phase of grafting.
2. A biomimetic biomaterial, developed by the academic partner University of Brighton (UK), able to mimic the natural extracellular matrix of a pancreatic islet and capable of driving the tissue-like assembly of pancreatic cells and vascular endothelial cells in to a tissue engineered pseudo-islet.
3. Two types of microgravity static and portable bioreactors, developed by the industrial partner CELLON (L), enabling the assembling of the biomaterial/cell constructs in suspension and their transportation to the nosocomial unit, respectively.
The expertise offered by the industrial partner AvantiCell Science (United Kingdom) and two centres for organ transplantation, ISMETT (Italy) and University of Geneva European Registry for Pancreatic Islet Transplantation (Switzerland) allowed the validation of all the components and final constructs by advanced in vitro and in vivo methods.
The partners made substantial progress towards the optimisation of the bioengineered pancreatic islets, called biochip, capable to partially revert diabetes in a well-established mouse syngenic model.
Project Context and Objectives:
NEXT main goal was to provide a breakthrough technological alternative to pancreatic islet transplantation (PIT). Currently, PIT is widely recognised as the treatment of choice for Type 1 Diabetes patients who are no longer responsive to insulin administration or who do not experience symptoms of hypoglycaemia. Thus far, these clinical conditions can be treated only with either whole organ transplantation or PIT. The shortage of organ donors makes PIT a very attractive alternative treatment, where islets isolated from cadaveric donors are infused in the liver portal vein of the recipient through a relatively simple and minimally-invasive procedure. However, it is known that regardless of the immunosuppressant therapy associated to their transplantation, most of the transfused islets lose their viability during the first week of grafting in the portal vein because of the immune response, oxidative stress and lack of vascularisation.
NEXT technology developed a tissue engineering pancreatic pseudo-islets to reverse diabetic conditions. The innovative aspect of this project stemmed from the unique combination of the following construct components:
1. A recombinant immunosuppressant protein that could be release locally at the site of transplantation to protect the islets during the early phase of grafting
2. A biomimetic biomaterial capable to mimic the natural extracellular matrix of a pancreatic islet and capable of driving the tissue-like assembly of pancreatic cells and vascular endothelial cells in to a tissue engineered pseudo-islet.
3. Two types of microgravity static and portable bioreactors enabling the assembling of the biomaterial/cell constructs in suspension and their transportation to the nosocomial unit, respectively.
The envisaged final product uniquely combines the properties of:
i) mimicking the extracellular matrix present in the pancreatic islets and encouraging the assembly of the beta cells and endothelial cells into structures similar to natural pancreatic islets.
ii) presenting peptides able to induce localised immunosuppression and hence protection from the host response during the early phases of transplantation.
Project Results:
Figure 1 represents the most promising project foregrounds achieved during project implementation.
Figure 1. NEXT’s innovation pipeline
Most notably, the following S/T results were obtained:
i) ACS developed and validated a new cell-based fibrosis assay that will be marketed by ACS in EU from January 2018, and subsequently in other geographic markets. At time of writing, the new service is expected to generate sales between 20 and 40keuro in 2018 fiscal year. This will be followed during calendar year 2018 by a cell-based fibrosis assay kit built upon the same technology.
ii) EXP developed and validated a modular cloning method that is currently marketed by EXP in EU (www.doulix.com). At time of writing, the new service is expected to generate sales between 10 and 15 keuro in 2017 fiscal year.
iii) EXP has signed a world-wide agreement with Agilent Technology Inc for the joint commercialization of products related to DOULIX in USA. At time of writing, the new service is expected to generate sales in excess of 100 keuro in 2018 fiscal year.
iv) EXP has file an international trademark application (Int.Reg. No.1351473) and obtained the trademark “DOULIX – Your toolkit for synthetic biology” for EU (TM nr. 016125577), and USA (TM nr. 79210558). JP application is currently under review.
v) EXP file and obtained a patent for the expression of human recombinant protein in bacterial host (patent nr. IT-1428672, issued on 24 May 2017, valid through 12 February 2035). At time of writing, the new service is expected to generate sales in excess of 100 keuro in 2018 fiscal year.
vi) UoB developed and validated synthetic biomaterials as substrates for pancreas-on-chip assembly. At time of writing, UoB aims to exploit it either through the filing of a patent or through a confidential manufacturing know-how that will be licensed to a start-up company.
vii) CELLON has been promoting their bioreactors as such or in combination with UoB synthetic biomaterials for the culturing of human pancreatic islets and received positive feedback from beta testers.
viii) CELLON has also achieved a proof of concept of islet transport by vehicle using a battery-driven microgravity rotatory bioreactor.
Potential Impact:
The NEXT project proposes a revolutionary technology for improving survival and efficiency of PITX that could be translated to artificial organ construction. Engineering for self-defence the same target cells and assembling them into a chimeric artificial organ may allow cell transfusion/transplantation or bioartificial graft transplantation in the absence of lifetime immunosuppressant therapy. This strategy would dramatically reduce costs of this treatment; it would allow the treatment of non-complicated diabetes by means of functional transplantation (Pancreatic islet) without requiring solid organ transplantation (kidney) and corresponding immune-suppression treatment. The concept of Bio artificial chimeric organ offers a breakthrough in the field and, if successful, will open a new area which can also be expanded in the generation of xenogeneic artificial organs which could overcome the issue of cadaveric organ shortage. The main expected result is the construction and validation of the bioCHIP as described in section 1.
This high risk-high gain goal is complemented with a robust contingency plan that will concentrate on engineering a bioartificial functionalized pancreatic islet, which will still offer huge advantages in terms of efficacy (by reducing the amount of harvested and transplanted islet) and safety (by avoiding systemic immunosuppression).
The World Health Organisation has estimated that 171 million people were affected by diabetes worldwide in 2000 and predicts that 30 million people will be diagnosed with Type 1 diabetes worldwide by the year 2025 (Diabetes Care 2005, 28, 2130–2135). The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2 % of all deaths. Excess mortality attributable to diabetes accounted for 2–3 % of deaths in the poorest countries and over 8 % in the U.S. Canada, and the Middle East. In people 35–64 years old, 6–27 % of deaths were attributable to diabetes. These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death. Diabetes accounts for at least 10 % of total health care expenditure in many countries. However, routinely reported statistics based on death certification seriously underestimate mortality from diabetes, because individuals with diabetes most often die of secondary cardiovascular and renal complications and not from a cause uniquely related to diabetes, such as ketoacidosis or hypoglycemia.
Direct medical expenditures alone totaled $ 91.8 billion and comprised $ 23.2 billion for diabetes care, $ 24.6 billion for chronic complications attributable to diabetes, and $ 44.1 billion for excess prevalence of general medical conditions. Inpatient days (43.9 %), nursing home care (15.1 %), and office visits (10.9 %) constituted the major expenditure groups by service settings. In addition, 51.8% of direct medical expenditures were incurred by people >65 years old. Attributable indirect expenditures resulting from lost workdays, restricted activity days, mortality, and permanent disability due to diabetes totaled $ 39.8 billion. U.S. health expenditures for the health care components included in the study totaled $ 865 billion, of which $ 160 billion was incurred by people with diabetes. Per capita medical expenditures totaled $ 13,243 for people with diabetes and $ 2,560 for people without diabetes. When adjusting for differences in age, sex, and race/ethnicity between the population with and without diabetes, people with diabetes had medical expenditures that were approximately 2.4 times higher than expenditures that would be incurred by the same group in the absence of diabetes.
Visiongain Ltd predicts that the retail market for diabetes medications will continue to show significant growth for what is an already large market. Actos from Takeda is the leading oral anti-diabetic product and appears set to retain this status. However, it is co-marketed with Eli Lilly which has new products to make available. Lantus from Sanofi-Aventis is the leading insulin product. However, the diabetes market is characterized by high unmet need and treatment issues. At the same time, these issues along with radical changes in the understanding of diabetes, have created an environment rich in opportunity. Among them, the alternative treatment based on pancreatic islet transplantation seems to be considered by the experts to be the most attractive
Currently, the rate of pancreatic organ donation is insufficient to allow even 0.1 % of those that could currently benefit from islet transplant therapy to have this treatment option. Recent improvements in the success rate of islet transplantation have provided critical proof of principle that restoration of functional cell mass in patients with Type 1 diabetes can reverse the disease and allow patients freedom from the burden of daily insulin injections. With the advent of the Edmonton Protocol, standard operating procedures for islet purification and delivery are established, and islet transplant centres around the world have been able to reproduce the success of this protocol. The recently established UK Islet Transplant Consortium has brought together all the major UK islet transplant centres, with a view to advancing European islet transplant success rates to those currently achieved in North America.
The main novelties that characterized the NEXT concept are:
• BT1: Inducing local and transient immunosuppression by coating pancreatic islet with immunosuppressive peptides (ISPs). As preferred embodiment, ISPs are conjugated to lysine dendrimers capable of binding β-cells.
• BT2: Reducing host immunorejection against islet graft by encapsulating donor β-cells islet with polymer matrix congaing recipient endothelial cells. As preferred embodiment, donor β-cells islet is encapsulated in VEGF-containing chitosan nanoparticles, which attract recipient progenitor endothelial cells.
• BT3: Increase artificial islet survival rate by culturing them under microgravity conditions.
We envisage two different exploitation strategies:
i) long-term exploitation strategy for the envisaged NEXT artificial pancreatic islet that is expected to reach the market after project completion and no earlier than 5-7 years;
ii) short-term exploitation strategy for intermediate results achieved during the first 36 months that are expected to reach the market within 1-2 years.
As far as long-term exploitation strategy is concerned, the ultimate objective of the NEXT project is to develop a chimeric artificial pancreatic islet capable to escape recipient’s immune response by virtue of vasculature chimerism and physical immune-shielding. Within this framework the envisaged technology fall under the advanced therapy medicinal product (ATMP) category according to Directive 2001/83/EC as amended by the ATMP Regulation 1394/2007. The envisaged technology represents a high-risk/high-gain breakthrough that targets a multi-million dollar market. In addition, the envisaged NEXT’s technology may be exploited for other solid organ transplantation thus targeting a potential global market for valued at nearly $54 billion in 2010 and projected to grow at an 8.3% compound annual growth rate (CAGR) to reach $92 billion in 2017 [Source: BBc Research]. Within this framework and in perspective of the results obtained in vivo (see WP4), the Consortium proactively sought partnership with VC funds for the creation of a NewCo in EU for the exploitation of results in Europe, USA and JP. At the time of writing, the revenues sharing model for the NewCo foresees:
• opt-in for NEXT’s SMEs partners as shareholders of NewCo. Within this framework, funding SMEs will grant exclusive right for the use of their respective background to the NewCo. Alternatively, SMEs may act as service and product provider to the NewCo under terms to be negotiated.
• Fixed-fee agreement for the non-exclusive right to use UoB’s dendron. Alternatively, UoB may act as raw material provider under terms to be negotiated.
• Fee-for-service and milestone-based royalties for UniGE and ISMETT based on work performed to progress NEXT’s technology up to first-in-human.
As far as short-term exploitation strategy is concerned, Figure 1 represents the most promising project foregrounds achieved during project implementation.
Most notably:
Capitalising on the results so far achieved, the project Steering Committee has identified intermediate products and clear commercial benefits for the industrial partners:
i) AvantiCell has demonstrated the suitability of their tests to measure in a reliable manner the viability of beta cells and pancreatic islets prior to transplantation. The company has also optimised a commercially-viable procedure for the isolation of endothelial cell progenitors from human peripheral blood. Relevant to the prediction of the immune response to tissue engineering constructs, ACS has also developed a predictive in vitro model for fibrosis.
ii) Explora has developed an immunosuppressant recombinant protein that has the potential of being used in clinical applications beyond islet transplantation.
iii) CELLON has proven the efficacy and adaptability of their bioreactor in assembling bioengineered islets as well as in ensuring the survival and functionality of islets upon a clinically-relevant period of time.
List of Websites:
www.thenext-project.eu