Specialist in tissue analysis by Histology, Immunohistochemistry and In Situ Hybridization TECHNOLOGIES & SERVICES FOR THERAPEUTIC ANTIBODY DEVELOPMENT
CONTENTS Histalim: who we are Our areas of expertise Our services for discovery Our services for preclinical study Our services for clinical study Contact p4 p5 p6 p8 p9 p10 2
Human-Xenograft-Immunohistochemistry HER2
Who we are Founded in 2005 Facilities in France (Montpellier) and in Germany (Berlin) Specialises in designing, carrying out and validating innovative technologies in histological assays, immunohistochemistry, in situ hybridization and image analysis Dedicated to accelerate and facilitate development of novel pharmaceuticals, medical devices and diagnostic tools. Particularly engaged in developing new therapies (e.g., antibody drug conjugates) and diagnostic tools (e.g. companion diagnostics) in the areas of: oncology, autoimmune and cardiovascular diseases GLP compliant and authorized to carry out studies on human tissue samples Have extensive experience in processing and analyzing artificial tissues (e.g., reconstructed epidermis) and inert materials (e.g., artificial organs, implants, biocompatible polymers ). Clients include life sciences and healthcare companies; dermo-cosmetic companies; the food industry and environmental organizations. 4
Our areas of expertise supporting mab development 5
Our areas of expertise supporting mab development State-of-the-art histology / immunohistochemistry equipment Immunohistochemistry staining is performed using automata that guarantees constant quality and fast processing of large numbers of human or animal tissue samples. Access to international network of 15 biobanks for some of the rarest normal and diseased human tissues. 6
Our specialized services I : DISCOVERY Identification and validation of biomarkers for therapeutic and diagnostic applications Use of tissue-based solutions to identify and validate different biomarkers (pharmacodynamics/predictive, diagnostic or prognostic) on normal and diseased human or animal tissue samples. Development of diagnostic tests on patient samples (e.g., tumor samples). Such companion tests can be used as screening assays in clinical trials. Access to rare human tissue samples provided : Nk/T lymphoma, Lupus, Crohn s disease, COPD etc. through a network of 15 biobanks worldwide. Immunohistochemistry and ISH staining using Roche-Ventana automata (the reference in clinical pathology). Analysis of results by custom tools for image analysis or through an European network of pathologists. 7
Our specialized services I : DISCOVERY Identification of biomarker combinations and evaluation of their diagnostic relevance: A novel way to conceive and develop biomarkers. Selection of biomarkers by comparing a voluminous range of heterogeneity descriptors (i.e., textural, morphological and structural features ) with reference data (the pathological diagnosis as gold standard). High throughput tissue screening: Protocols are based on Tissue MicroArrays (TMA) to carry out In-Situ screenings (up to 300 tissue spots per slide). Can test large panel of tissue samples (cross-reactive or not) and numerous antibody candidates simultaneously on the same slide. Particularly efficient technique offering additional benefits to flow cytometry. Can identify undesirable In-Situ cross-reactivity early in development. Screening Preclinical validation Clinical validation 8
Our specialized services I : DISCOVERY Identification of a combination of biomarkers and evaluation of their diagnostic relevance: Pathway characterization and antibody reactivity study by multiplex IHC / ISH: In-Situ multiplex using IHC / ISH enables study of immune complexes and the cellular reactions triggered by binding antibody on specific targets. Powerful early validation tool to explore the cellular MoA of therapeutic antibody or cell therapy on both proteomic and genetic scale. Immune complex interaction study: After identification of the antibody and its target, assessing the stability of the immune complex and tissue reactivity linked with target polymorphism is important to identify / understand potential undesirable cross-reactivities. 9
Our specialized services II : PRECLINICAL STUDY Identification of biomarker combinations and evaluation of diagnostic relevance: Histopathological examinations of animal tissues or xenografts for preclinical in vivo efficacy and toxicology studies Biodistribution/pharmacological studies Animal model validation Tissue Cross-Reactivity (TCR) assays on Tissue Microarrays (FFPE or frozen TMA) for pre-screening or on regulatory full tissue panels (FDA and EMEA compliant) Access to expert pathologists network Antibody specificity assessment on animal and human tissues (GLP) : Cross-reactivity studies for therapeutic antibodies on tissue sections - detect undesirable reactivity in order to qualify potential toxicity Projects conducted under GLP conditions if required Optimization and validation of the immunolabelling : All immunostainings are performed with automated equipment (i.e., Roche- Ventana Discovery and Benchmark automated staining instruments) Develop, validate and optimize IHC staining protocols with +/-ve tissue/target controls; negative (isotype) control for antibody specificity assessment; assay control slides to assess background staining 10
Our specialized services II : PRECLINICAL STUDY Preliminary study : A preliminary study prior to a regulatory study to reveal any crucial information that might completely derail the project is recommended A tailor-made reactivity and cross-reactivity studies is offered to obtain speedy information on the antibody These tests can be performed on: Tissue MicroArray (TMA) slides Tumor tissue panels Healthy tissue panels Animal tissues Human tissues Tailor-made cohorts of tissues Regulatory study: Performed on human tissues under GLP conditions to establish the preclinical dossier and to ensure the therapeutic antibody can enter the clinical phase 11
Our specialized services III : CLINICAL STUDY Phase I: human biopsies pre- / post-treatment histopathological study Our pathologists (D.M and D.V.M.) can take part in clinical projects by carrying out histopathological examinations of tissues removed from patients before and after treatment Histalim supplies standardized analytical protocols; acts as central laboratory for patient tissue collection in multi-centric assays, and conduct the histopathological examinations of tissue samples or biopsies 12
Our specialized services III : CLINICAL STUDY Clinical validation of In Vitro Diagnostic devices Allows empirical evaluation of clinical utility and added-value in patient care Deemed positive if results of the test enables fast, effective decision making, regarding the treatment and the provision of preventive measures for the patient Qualitative or quantitative objective indicators are established for evaluating the impact of the in vitro diagnostic device: Advanced analytics provided by the test (biomarker without precedent, companion diagnostics, an earlier equivalent with new advantage, etc.) Clinical value of the result (impact on clinical decision making) Analytical reliability of the test in an actual clinical environment Ease of incorporation of the in vitro diagnostics during patient care (sampling method, routine time to obtain results, etc.) Impact on the risks encountered by the healthcare personnel Overall production cost (investments, fixed & variable costs, working hours of health personnel) Economic impact on the health care system and social impact Clinical information and validation data are compiled for regulatory filing: To obtain CE-IVD marking at EMA For FDA submission - Evaluation and Safety In all countries, these data are indispensable for reimbursement considerations 13
Summary Our Offer The only structure in Europe 100% specialized on tissue analysis Capability to support projects from research through development to regulatory phases Early protocol validation on clinical automata (Roche-Ventana) Continual R&D to offer innovative technologies linked to market needs (image analysis, screening protocols, digital pathology ) Our Partnerships Etablishment of comprehensive expert network for the needs of each project: D.M and D.VM Patologists (>30 worldwide) Experts for proteomic assay, in-vivo assay, biobanking research etc. Reactivity and availability for each project Established track record in complex projects for different industrial partners: big pharma, midsize pharma, biotech, IDIV, medtech etc. 14
HISTALIM 126, rue Emile Baudot 34000 Montpellier FRANCE tel : +33 (0)4.67.712.765 Christ SERRA Head of Business Development cserra@histalim.com