Company overview

Summary

Our group at the University of Navarra has generated a collection of pre-clinical mouse models that accurately recapitulate the principal features of human multiple myeloma (MM) and B-cell lymphomas. Using these models in the Martinez-Climent lab, we are starting to unravel the sequential interplay between the tumor cell and the immune and non-immune microenvironment at unprecedented levels. In this context, we have set up preclinical therapy trials in genetically and immunologically diverse MM models to evaluate immunotherapy combinations, defining biomarkers of therapy response that were validated in two clinical series of MM (1). We have also established models for clinical indolent and aggressive B-cell lymphoma subtypes, which have been used to decipher how particular lymphoma microenvironment subtypes condition responses to chemo-immunotherapy in mouse models and clinical series (2). A second step has been to make our models closer to humans, by selective replacement of endogenous mouse genes coding for therapeutic target proteins by human ortholog gene sequences. As proof-of-concept we have developed mouse models with human CRBN, BCMA and GPRC5D expression in the tumor cells and CRBN and CD3 in the T-cell compartment, which allow testing clinical immunotherapy such as IMiDs/CELMoDs, CAR T cells and TCEs that otherwise cannot be tested in mouse systems. Critically, studies in mice are integrated with data from MM patients in collaboration with our clinical colleagues at the University of Navarra, aiming to provide scientific information with immediate clinical impact (3-5). Using our models, we have established collaborations with research groups from European and American top universities focused on MM and lymphoma. In addition, we have signed and executed 15 research agreements with major pharmaceutical companies in the last 3 years, with the goal of investigating preclinical and clinical agents for hematologic malignancies. We think our models constitute the next level of preclinical research that may translate scientific knowledge to clinical trials.

Mimo Biosciences, a spin-off of the university of navarra

In February 2024 we founded MIMO Biosciences, a start-up of the University of Navarra directed by Ricardo Perez-Merino, MBA (CEO), with Dr. Marta Larrayoz as R&D Director and Prof. Martinez-Climent as CSO. Knowhow, technology, models and IP rights have been licensed from M-Climent´s lab to MIMO, which has the mission of providing research services to academic and pharmaceutical partners in MM, lymphoma, and related fields. With a highly qualified scientific and management team of 7 employees, and with three research contracts with two pharmas already in place, MIMO has launched an ambitious program to develop newly designed, proprietary models of genetically diverse MM with multiple humanized targets.
These new models recreate clinical situations that require more effective therapies, such as high-risk MM with TP53 loss, genetic instability, or t(4;14), VRD and BCMA-targeted refractory states, extramedullary disease, and light-chain amyloidosis. In parallel, MIMO is generating patient-derived xenograft (PDX) models from MM patient samples engrafted into IL6-secreting immunodeficient mice reconstituted with a human immune system. The goal of the humanized PDX is to directly study clinical immunotherapy agents that cannot be tested in other experimental systems. These new models will be available by Q1-Q2 2025. Additionally, MIMO is expanding the generation of humanized mouse and PDX models for the principal B-cell lymphoma subtypes (DLBCL, FCL, LPL/WM, MZL/MALT lymphoma), as well as for acute myeloid leukemia (AML), which will be sequentially available by Q2-Q3 2025. As proof-of-principle, DLBCL of ABC and GCB subtypes with humanized CD19 or CD20 and CD3ε are being used to evaluate TCE and CAR T-cell therapies, while AML PDXs are serving to test targeted agents and immunotherapy combinations. Our expectation at MIMO is that such optimized, complementary mouse and human platforms will broaden and strengthen research collaborations with pharmaceutical companies for addressing virtually all scientific and clinical issues in hematology/oncology. Now located at the University of Navarra CIMA building, in Q1 2025 MIMO will move to its own state-of-the art research facilities currently under construction within the University of Navarra campus. Close to the Schools of Medicine, Science and Pharmacy, the Clinica University of Navarra hospital and CIMA buildings, MIMO and the University of Navarra have signed a collaboration agreement for the interchange and use of a wide range of services, including multiparametric flow cytometry, cell sorting, high-throughput and single-cell genomics, micro-CT and micro-PET imaging for rodents, surgery, histopathology, toxicology, human tissue bank, and computational data resources. MIMO counts on an international advisory network with key opinion leaders in hematology, oncology and immunology. Our final goal at MIMO is to become the preferred partner of pharmaceutical companies for preclinical research in cancer.

Modeling Science for Cancer Therapy