The consortium aims to commercialise the MMpredictor as a personalised medicine tool that predicts the most effective treatment strategy for individual Multiple Myeloma (MM) patients. MM is the second most common form of blood cancer contributing to 15% of all blood cancers and ~1,5% and 2% of all cancer deaths annually in the EU and US, respectively. Patients show a large variability in treatment response and side effects due to tumour heterogeneity and the patient’s intrinsic characteristics. Therefore, not every treatment will be suitable for each patient, and treatment strategies are often based on trial-and-error. The availability of multiple (>20) treatment options complicates treatment decision-making even more. With the current development of many more promising treatments, there is an urgent unmet clinical need for a diagnostic assay that supports personalised cancer treatment in order to improve patient health outcomes, prevent side effects and reduce healthcare costs. SkylineDx has previously developed the MMprofiler, a microarray-based diagnostic test that can subtype MM patients and reliably predict MM patient survival (prognosis). In this project, the test’s clinical value will be expanded to include the prediction of treatment effectiveness in individual patients based on Gene Expression Profiling. An addendum for new intended use will be filed to the current in vitro diagnostic (IVD) registration, while renaming the test to MMpredictor. The project will also focus on positioning the test as a cost-effective IVD test for personalised medicine, that will increase health outcome and quality of life of patients and reduce healthcare costs. The consortium consists of a life science SME specialised in molecular diagnostics, clinical centres with world renowned KOLs, a leading health economic institute, and a European MM patient advocacy organisation combining all the required complementary expertise to successfully bring the MMpredictor to market.

ASCERTAIN (Affordability and Sustainability improvements through new pricing, Cost- Effectiveness and ReimbursemenT models to Appraise iNnovative health technologies) addresses the need of patients, physicians, payers, regulators, and manufacturers to improve the affordability and accessibility to innovative health technologies (including pharmaceuticals) in Europe. ASCERTAIN aims to enhance current methods of (value-based) pricing, cost-effectiveness modeling, threshold-setting, reimbursement, and payment, to set affordable prices, and to facilitate a cyclic assessment of broader societal benefits including costs and risks. It seeks to find a sustainable balance between access to affordable technologies, the need to stimulate innovation and entrepreneurship, and the need to consider the environmental impact of innovations. Guided by a conceptual framework integrating pricing, health technology assessment and reimbursement/payment, ASCERTAIN will develop open-access, easy to use, policy-supporting tools including (i) pricing models, (ii) value assessment models, and (iii) reimbursement models, which will be adaptable to country-specific conditions. These tools will improve transparency and accountability of decision-making, reduce uncertainty for all stakeholders, reward innovation in areas of high unmet need, accelerate access for patients, and support long-term planning in a sustainable way. Further, these tools will be developed, tested, and validated for three use cases, including precision cancer medicine, cell- and gene therapy, and medical devices (class IIb and III) or in vitro diagnostic (IVD) class D. The multinational, multidisciplinary ASCERTAIN consortium is complemented by an international advisory board consisting of key stakeholders, with whom the policy-supporting tools will be co-created. All tools will be hosted on a cloud-based, publicly accessible, user-friendly platform following open science principles.

CARAMBA is proposing to use the revolutionary CAR-T cell technology to tackle multiple myeloma, a rare and incurable hematologic malignancy. Myeloma is associated with a substantial socioeconomic burden and there is a strong demand by patients, their families and caregivers for a curative myeloma treatment. The CARAMBA investigators will conduct a phase I/II clinical trial of immunotherapy with patient-derived T cells that are engineered to express a synthetic chimeric antigen receptor (CAR) specific for the myeloma antigen SLAMF7. SLAMF7 is uniformly expressed on all myeloma cells in every patient, and SLAMF7 CAR-T cells will be equally effective in women and men. The efficacy and safety of SLAMF7 CAR-T cells has been validated by the coordinator in comprehensive pre-clinical testing which highlighted their unprecedented curative potential. SLAMF7 CAR-T cells have received an orphan designation for the indication multiple myeloma by the EC. The successful conduct, rapid and complete recruitment into the clinical trial is ensured by participation of 4 clinical myeloma centres of excellence in 4 EU member states, and the largest myeloma patient advocacy group in Europe, MPE. The SME partners in CARAMBA are prepared to develop the SLAMF7 CAR product all the way to market authorization. CAR-T cell therapy has been recognized as a ‘Breakthrough Therapy’ and clinical proof-of-concept obtained with CD19 CAR-T cells in leukemia and lymphoma. CARAMBA is building on novel and proprietary, cutting-edge CAR technologies including virus-free Sleeping Beauty CAR gene-transfer from DNA minicircles which substantially reduces the cost of CAR-T cell manufacturing, making it an economically viable and sustainable medicinal product. We are confident, that if funded, CARAMBA will accomplish its objective to establish the role of CAR-T cell therapy as a therapeutically effective, commercially attractive and socioeconomically desirable treatment in myeloma and other rare diseases.

Measuring and quantifying how a patient feels or functions during treatment is an important endpoint in cancer clinical trials. It is generally accepted that the collection of PRO data in cancer clinical trials allows the inclusion of the patient’s voice in the risk-benefit assessment of therapies. However, no standards exist on how to analyse, interpret or report health-related quality of life (HRQOL) and other patient-reported outcomes (PROs). This initiative wants to pursue efforts in addressing the urgent need for standardization, by setting clear and validated standards that are tailored to and endorsed by all relevant stakeholders. With a strong international and multi-stakeholder Consortium, the initiative aims at finding consensus on suitable methods to analyse valid PRO objectives in cancer randomized clinical trials (RCTs) and ways to communicate these PRO findings in a standardized way that is understandable to all. To achieve this aim, SISAQOL-IMI will identify valid PRO research objectives and match these with appropriate statistical methods for PRO analysis in cancer RCTs. Translation to the estimands framework will be provided. Furthermore, the possibility of extending these recommendations to single-arm trial designs will be explored. Recommendations on clinically meaningful change for PRO instruments, as well as design considerations and ways for assessing quality of collected PRO data will be developed, and tools and templates for presentation and visualization of PRO findings freely made available. Strong emphasis is put on continuous collaboration with patient advocacy representatives throughout the project. Increased interpretability, adoption and full use of PRO outcomes for all stakeholders is expected by providing consensus-based and validated recommendations and communication tools for PRO data, ultimately resulting in better communication and shared decision making, improved outcomes, treatment satisfaction and care.

This project aims to create a multi-scale patient-specific human virtual twin for patients who are eligible for CAR T cell therapy, which can be extended to cellular immunotherapies in general. The virtual twin will be fully integrated into the ecosystem under the Digital Europe Programme and will be available as a research-use-only prototype in relevant application environments with technology readiness level 6. The virtual twin will support decision-making throughout the patient's journey, from diagnosis to pre-treatments, cellular immunotherapy, and late patient monitoring. This will enable patients and health experts to identify the most effective course of therapy. The virtual twin for cellular immunotherapies will take multi-scale modelling to the next level by providing methodological concepts for integrating "living drugs" such as CAR T cells into the human virtual twin ecosystem. To achieve this goal, the project builds on existing data models for hematological malignancies and multiple myeloma (MM) to create a virtual twin for CAR T cell therapy for MM patients. The implementation process follows software development principles for software as medical devices, ensuring the exploitation of the research-use-only prototype. Patient's, SSH, gender differences, and other stakeholders' perspectives are fully integrated into the design, specification, and implementation process. Throughout the implementation process, a modular software architecture and extensible ontologies/terminologies are utilized, making the reference model easily transferable to other indications that can be treated with CAR T cell therapy or other cellular immunotherapies. Overall, the CERTAINTY virtual twin will provide decision support for patients and health experts, improving the effectiveness of cellular immunotherapies and advancing precision medicine.