Periodic Reporting for period 3 - ONCOSMART (ONCOlogic patient profiling and personalized treatment through SMART bedside diagnostics)
Reporting period: 2020-09-01 to 2021-08-31
Every year about 20 million people are diagnosed with cancer and about 10 million cancer patients see their disease advancing and becoming hard to treat, e.g. refractory to treatments and/or developing metastases. At the same time 95% oncology trials fail mainly because of a lack of efficacy of the new treatment. There is an urgent need to better match patients and drugs. Precision medicine based on genomic profiling can be applied only to about 15% of advanced cancer patients and eventually provide a benefit to less than 10% of “hard-to-treat” patients. Moreover, last-generation cancer immunotherapies, which act by arming the immune system to target tumor cells, feature complex mode of actions which cannot be captured by traditional precision medicine.
Functional precision medicine is an emerging approach consisting in the analysis of how live tumor cells extracted from patients react to the interaction with candidate drugs or immune cells in-vitro. This approach has shown a high predictive power, superior to molecular/genomic profiling, making it a valid technique to identify effective and personalized treatments. Two great advantages are the possibility to profile a patient independently from the genetic makeup and the compatibility with a wide range of treatments, from chemotherapies to targeted- and immune-therapies. However, functional tests still have limited clinical validation and adoption since they are available only as a laboratory test as no tools exist to automate and standardize their execution.
ONCOSMART key objective is to develop the first fully automated and standardised platform for functional precision medicine and to validate its analytical and clinical performance in predicting patient’s response to treatments. First target are hematologic tumors, primarily acute myeloid leukemia (AML), with the following objective to extend the platform use to other hematologic and solid tumors within future developments.
A first goal is to de-centralize the execution of functional profiling tests promoting their adoption in research and clinical labs. A second goal is to generate a tool helping biopharma companies and clinical research institutes in developing innovative cancer immunotherapies – including cell therapies and antibody-based treatments – more efficiently, with reduced failure risk and at a fraction of the cost.
Functional precision medicine is an emerging approach consisting in the analysis of how live tumor cells extracted from patients react to the interaction with candidate drugs or immune cells in-vitro. This approach has shown a high predictive power, superior to molecular/genomic profiling, making it a valid technique to identify effective and personalized treatments. Two great advantages are the possibility to profile a patient independently from the genetic makeup and the compatibility with a wide range of treatments, from chemotherapies to targeted- and immune-therapies. However, functional tests still have limited clinical validation and adoption since they are available only as a laboratory test as no tools exist to automate and standardize their execution.
ONCOSMART key objective is to develop the first fully automated and standardised platform for functional precision medicine and to validate its analytical and clinical performance in predicting patient’s response to treatments. First target are hematologic tumors, primarily acute myeloid leukemia (AML), with the following objective to extend the platform use to other hematologic and solid tumors within future developments.
A first goal is to de-centralize the execution of functional profiling tests promoting their adoption in research and clinical labs. A second goal is to generate a tool helping biopharma companies and clinical research institutes in developing innovative cancer immunotherapies – including cell therapies and antibody-based treatments – more efficiently, with reduced failure risk and at a fraction of the cost.
In the first part of the project, Cellply completed the development of a Beta version of the platform, then industrialized the first production system composed of i) an instrument automating the analytical process from sample staining to in-vitro stimulation with drugs and fluorescence microscopy imaging, ii) a microfluidic device generating and processing thousands of miniaturized co-cultures where live tumor cells interact with molecular drugs and immune cells, iii) disposable kits containing all the reagents needed for the test and iv) analytical software powered by machine learning to extract a massive amount of single-cell multiplex data from each analysis.
In the second part of the project, the system was verified and validated by determining the analytical performance and clinical performance in a clinical study carried out in collaboration with the University of Bologna – Policlinico Sant’Orsola, the Charité hospital in Berlin, the Ravenna hospital and the IRST oncology institute in Forlì-Cesena. The study retrospectively evaluated the in-vitro sensitivity of AML patients’ tumor cells to standard of care drugs comparing it with the actual hematological response and resulted in demonstrating a high accuracy in predicting the clinical outcome.
Taken together, these results eventually allowed to generate the technical files needed for CE-IVD certification.
The platform was also specialized during the project through the development of an innovative patent-pending method for the deep characterization of immune-tumor cell interactions. Several collaborations established with biopharma companies and institutes during the project demonstrated that platform has unique features making it a powerful tool to support the discovery and development of novel cell therapies (e.g. T and NK cell therapies, such as CAR-T and CAR-NK) and monoclonal antibodies, by generating unique single-cell multiplex data which help understanding the functional and phenotypic characteristics of cell subpopulations within immune cell batches from patients and donors. Tested tumor models include acute and chronic leukemias and multiple myeloma.
In the second part of the project, the system was verified and validated by determining the analytical performance and clinical performance in a clinical study carried out in collaboration with the University of Bologna – Policlinico Sant’Orsola, the Charité hospital in Berlin, the Ravenna hospital and the IRST oncology institute in Forlì-Cesena. The study retrospectively evaluated the in-vitro sensitivity of AML patients’ tumor cells to standard of care drugs comparing it with the actual hematological response and resulted in demonstrating a high accuracy in predicting the clinical outcome.
Taken together, these results eventually allowed to generate the technical files needed for CE-IVD certification.
The platform was also specialized during the project through the development of an innovative patent-pending method for the deep characterization of immune-tumor cell interactions. Several collaborations established with biopharma companies and institutes during the project demonstrated that platform has unique features making it a powerful tool to support the discovery and development of novel cell therapies (e.g. T and NK cell therapies, such as CAR-T and CAR-NK) and monoclonal antibodies, by generating unique single-cell multiplex data which help understanding the functional and phenotypic characteristics of cell subpopulations within immune cell batches from patients and donors. Tested tumor models include acute and chronic leukemias and multiple myeloma.
ONCOSMART is the first analytical tool that determines the effectiveness of anticancer drugs for a specific patient by testing live tumor cell response to one or multiple cancer drugs. The device has been validated on haematological cancers and analyses tumor and/or immune cells from bone marrow or blood samples from a specific cancer patient to provide a personalized report within 24-48 hours.
The solution is designed to support biopharmaceutical companies and clinics/hospitals, by accelerating the development of breakthrough therapies and by personalizing and optimizing their use on a patient-by-patient basis.
The system has been utilized in clinical settings where high-cost treatments, e.g. targeted therapies, combination regimens, molecular immunotherapies and cell therapies are in use. Therapy cost has reached, in many cases the range of €0.1-1 million per patient, posing a serious concern about economic sustainability and general access to latest-generation treatments. Healthcare expenditure in the EU is about €60 billion for cancer treatment, €6-8 billion only for blood cancers. The analytical system here developed can deeply impact on these costs and support value-based healthcare models providing payers with data-driven reimbursement strategies.
The latest application of the platform was related to cancer immunotherapies which represent the fastest growing segment in oncology. Cell therapy, in particular, is growing at an exponential rate with more than 2,000 products in development and more than 1,300 clinical trials, but has limited patient access due to the unsustainable cost for the healthcare systems. The platform accelerates the discovery and development of cancer immunotherapies with a market opportunity in the €3 billion range, growing to €9 billion by 2025 only for tests supporting the R&D of new therapeutic products in immuno-oncology and with future applications in the quality control and clinical testing settings.
The solution is designed to support biopharmaceutical companies and clinics/hospitals, by accelerating the development of breakthrough therapies and by personalizing and optimizing their use on a patient-by-patient basis.
The system has been utilized in clinical settings where high-cost treatments, e.g. targeted therapies, combination regimens, molecular immunotherapies and cell therapies are in use. Therapy cost has reached, in many cases the range of €0.1-1 million per patient, posing a serious concern about economic sustainability and general access to latest-generation treatments. Healthcare expenditure in the EU is about €60 billion for cancer treatment, €6-8 billion only for blood cancers. The analytical system here developed can deeply impact on these costs and support value-based healthcare models providing payers with data-driven reimbursement strategies.
The latest application of the platform was related to cancer immunotherapies which represent the fastest growing segment in oncology. Cell therapy, in particular, is growing at an exponential rate with more than 2,000 products in development and more than 1,300 clinical trials, but has limited patient access due to the unsustainable cost for the healthcare systems. The platform accelerates the discovery and development of cancer immunotherapies with a market opportunity in the €3 billion range, growing to €9 billion by 2025 only for tests supporting the R&D of new therapeutic products in immuno-oncology and with future applications in the quality control and clinical testing settings.