Periodic Reporting for period 2 - HepatoPredict (HepatoPredict, A decision tool for Liver Transplantation based on molecular signature)
Periodo di rendicontazione: 2021-05-01 al 2022-04-30
Liver cancer produces 782,000 deaths worldwide, with Hepatocellular Carcinoma (HCC) being responsible for more than 75% of these deaths. Surgical approaches have the best outcome and curative potential. Liver transplantation is the treatment of choice, however, stringent criteria have to be established to select patients, since healthy organs are scarce. Current criteria used for this selection, Milan and San Francisco criteria, only offer up to a 70% success rate. This number represents a large number of transplants performed in patients that do not benefit from the procedure, while at the same time not making organs available to patients that could be cured with a liver transplant.
We developed HepatoPredict, an innovative medical decision-making tool aimed at helping clinicians and surgeons to select patients with HCC for successful liver transplant. HepatoPredict achieves up to 94% precision, while at the same time identifying at least 30% more liver cancer patients that benefit from liver transplantation.
The main objective of this project was the optimization, industrialization and validation of HepatoPredict to prepare it to reach a global market. At the end of the project, Ophiomics has:
- completed the validation and industrialization of HepatoPredict as a kit to be used by pathology laboratories, as well as a laboratory-developed test
- completed the regulatory files for EU regulatory approval (CE IVD marking), which have been submitted shortly after the end of the project (May 2022)
- presented HepatoPredict in the plenary stages of major international conferences
- submitted the first, founding publication describing the method and its clinical validation (now accepted for publication in a top-tier journal); two other validation manuscripts are being prepared for submission within summer 2022.
- registered a prospective, interventional clinical trial that is recruiting patients and has already patents transplanted based on HepatoPredict decisions
- strengthened its IP
- signed a distribution deal for Europe with Biocartis and started commercial development
- initiated the development of a liquid biopsy version of HepatoPredict to facilitate wider adoption and other liver cancer-related products.
Overall, the grant allowed Ophiomics to move from preliminary results to a market ready product that is already under commercial development.
We developed HepatoPredict, an innovative medical decision-making tool aimed at helping clinicians and surgeons to select patients with HCC for successful liver transplant. HepatoPredict achieves up to 94% precision, while at the same time identifying at least 30% more liver cancer patients that benefit from liver transplantation.
The main objective of this project was the optimization, industrialization and validation of HepatoPredict to prepare it to reach a global market. At the end of the project, Ophiomics has:
- completed the validation and industrialization of HepatoPredict as a kit to be used by pathology laboratories, as well as a laboratory-developed test
- completed the regulatory files for EU regulatory approval (CE IVD marking), which have been submitted shortly after the end of the project (May 2022)
- presented HepatoPredict in the plenary stages of major international conferences
- submitted the first, founding publication describing the method and its clinical validation (now accepted for publication in a top-tier journal); two other validation manuscripts are being prepared for submission within summer 2022.
- registered a prospective, interventional clinical trial that is recruiting patients and has already patents transplanted based on HepatoPredict decisions
- strengthened its IP
- signed a distribution deal for Europe with Biocartis and started commercial development
- initiated the development of a liquid biopsy version of HepatoPredict to facilitate wider adoption and other liver cancer-related products.
Overall, the grant allowed Ophiomics to move from preliminary results to a market ready product that is already under commercial development.
Technical development, validation and industrialization has been concluded; clinical validation is sufficiently completed to support initial commercial development and is expected to continue in support of these commercial activities.
We finished the optimization of two versions of the HepatoPredict test (i) a kit version of HepatoPredict for use by pathology laboratories (primary version of HepatoPredict), a laboratory-developed test version, suitable for use in support of clinical research, quality control and back up for client laboratories. In both cases a cloud-based platform (MyOphiomics) allows access to the HepatoPredict.AI algorithm that generates a clinical report. Optimization procedures improved performance and usability of the original prototype, and included a detailed characterisation of the performance of the method that was the basis of the technical flies used for CE IVD marking. HepatoPredict achieved a precision of 94% (very high confidence mode), and a sensitivity of 130% (high confidence mode), using a non-trivial combination of variables and machine learning approaches, representing a significant improvement over existing clinical criteria and of the prototype at the beginning of the project.
We initiated the clinical validation procedures. In the retrospective setting we have completed the first cohort from CHULC (PT). We are currently validating on a cohort from another PT centre (CHUC). We have agreed terms and wait samples to arrive in July from H Henri Mondor (FR) and wait ethics approval for studies with with H de la Fe (ES) and Queen Elizabeth H (UK). The pandemic slowed us but the cohorts above serve to address all the validation needs raised by the hepatology/surgery community. In addition, we have discussed potential collaborations with several other hospitals in Europe, Asia and Americas, but these will be pursued in support of commercial development. Furthermore, we have, in collaboration with the CHULC (PT) designed, ethics-approved, registered and initiated a prospective clinical trial. 13 out of 40 patients were recruited and at least two were already transplanted.
We set up a manufacture laboratory and established a supply chain, detailed procedures compatible with the ISO13485 specifications (audit requested, pending), recruited and trained dedicated staff and can now support a business model based on a laboratory kit, with a manufacture capacity of 2000 kits/year and a roadmap for trebling this capacity. In addition, we set up a laboratory and formalised an extensive set of procedures that is now ready to support clinical studies, quality control activities and back up of client laboratories with an installed capacity for 5,000 samples/year, and a roadmap to doubling this capacity. This can also support an alternative business model of a laboratory-developed test.
We finished the optimization of two versions of the HepatoPredict test (i) a kit version of HepatoPredict for use by pathology laboratories (primary version of HepatoPredict), a laboratory-developed test version, suitable for use in support of clinical research, quality control and back up for client laboratories. In both cases a cloud-based platform (MyOphiomics) allows access to the HepatoPredict.AI algorithm that generates a clinical report. Optimization procedures improved performance and usability of the original prototype, and included a detailed characterisation of the performance of the method that was the basis of the technical flies used for CE IVD marking. HepatoPredict achieved a precision of 94% (very high confidence mode), and a sensitivity of 130% (high confidence mode), using a non-trivial combination of variables and machine learning approaches, representing a significant improvement over existing clinical criteria and of the prototype at the beginning of the project.
We initiated the clinical validation procedures. In the retrospective setting we have completed the first cohort from CHULC (PT). We are currently validating on a cohort from another PT centre (CHUC). We have agreed terms and wait samples to arrive in July from H Henri Mondor (FR) and wait ethics approval for studies with with H de la Fe (ES) and Queen Elizabeth H (UK). The pandemic slowed us but the cohorts above serve to address all the validation needs raised by the hepatology/surgery community. In addition, we have discussed potential collaborations with several other hospitals in Europe, Asia and Americas, but these will be pursued in support of commercial development. Furthermore, we have, in collaboration with the CHULC (PT) designed, ethics-approved, registered and initiated a prospective clinical trial. 13 out of 40 patients were recruited and at least two were already transplanted.
We set up a manufacture laboratory and established a supply chain, detailed procedures compatible with the ISO13485 specifications (audit requested, pending), recruited and trained dedicated staff and can now support a business model based on a laboratory kit, with a manufacture capacity of 2000 kits/year and a roadmap for trebling this capacity. In addition, we set up a laboratory and formalised an extensive set of procedures that is now ready to support clinical studies, quality control activities and back up of client laboratories with an installed capacity for 5,000 samples/year, and a roadmap to doubling this capacity. This can also support an alternative business model of a laboratory-developed test.
We developed a patient stratification tool to support liver cancer patient selection for liver transplantation. This is the fist market-ready tool that integrates tumour biology and clinical variables, significantly improving over existing clinical tools.
Adoption of HepatoPredict, due to highest sensitivity, will increase eligibility for curative intent transplantation to at least 30% more patients, which we believe will translate into more lives saved. A higher precision will enable reduction the number of non-curative transplantations and support the selection of the best therapy for each liver cancer patients, with gains in quality and quantity of life, in addition to less waste of organs and €€ in non-curative treatments. Finally, the HepatoPredict's two level architecture provides an objective criteria for optimal vs. non-optimal organ allocation.
HepatoPredict is now ready for commercialization and to tackle its global market. We have already signed a Europe-wide distribution agreement with BE-based Biocartis, a reference company in the cancer molecular pathology domain, and are now working with them to design a market entrance strategy, developing marketing materials and have already trained their full Europe-based business development team. At the same time, we have already established preliminary contacts for market entrance in the USA, Middle East and India.
HepatoPredict is our first product, but other are now following, with a patent, a scientific publication and a prospective proof of principle study ethics approved and starting patient recruitment for a second product. We are striving to become the global leaders in liver cancer precision medicine.
Adoption of HepatoPredict, due to highest sensitivity, will increase eligibility for curative intent transplantation to at least 30% more patients, which we believe will translate into more lives saved. A higher precision will enable reduction the number of non-curative transplantations and support the selection of the best therapy for each liver cancer patients, with gains in quality and quantity of life, in addition to less waste of organs and €€ in non-curative treatments. Finally, the HepatoPredict's two level architecture provides an objective criteria for optimal vs. non-optimal organ allocation.
HepatoPredict is now ready for commercialization and to tackle its global market. We have already signed a Europe-wide distribution agreement with BE-based Biocartis, a reference company in the cancer molecular pathology domain, and are now working with them to design a market entrance strategy, developing marketing materials and have already trained their full Europe-based business development team. At the same time, we have already established preliminary contacts for market entrance in the USA, Middle East and India.
HepatoPredict is our first product, but other are now following, with a patent, a scientific publication and a prospective proof of principle study ethics approved and starting patient recruitment for a second product. We are striving to become the global leaders in liver cancer precision medicine.