FACTSHEET Safety Assessment Aptuit is focused on streamlining and supporting the drug development process for biotechnology and pharmaceutical innovators worldwide by providing a comprehensive suite of drug discovery and development services and competencies. Aptuit can assist in designing development programs that compress timelines, maintain quality and reduce the costs of commercialization. Our unique ‘First in Man-enabling’ drug development program is based on ICH Guidelines, and includes the mandatory core battery of toxicology and safety pharmacology evaluations, providing the perfect solution in reaching early candidate selection decisions. Toxicology and Pathology Core Capabilities • Rodent, rabbit, dog and primate facilities • Custom designed investigative and Regulatory GLP core studies according to current international guidelines • GLP studies for Gene Therapy Medicinal Product and Biodistribution studies • Standard routes of administration (e.g. intravenous, oral, and subcutaneous routes) and special routes of administration (e.g. intranasal, intratracheal and intratechal) Safety Pharmacology Core Capabilities •C entral Nervous System: Modified Irwin test or functional observation battery in mouse, rat and dog. Pro-convulsant tests such as native tissue electrophysiology, in vivo studies of compound-inducing convulsions, potentiation of PTZ-induced convulsions, MEST Test and video-telemetry EEG in rat •A buse Liability testing: consulting on abuse liability strategy, 8-factors analysis, regulatory abuse liability package (self administration, drug discrimination, physical dependence/withdrawal, locomotor activity) •C ardiovascular System: in conscious (telemetry) and anaesthetised rodents (mouse, rat and Guinea pig), in conscious (telemetry) dogs and non human primates; cardiac safety in vitro panel including hERG, hNav1.5, hCav 1.2 in automated electrophysiology platforms and in manual patch clamp; in vitro assessment of selectivity and liability on GPCRs and ion channels (functional assay), enzymes and transporters (binding assay) •C ardiovascular and Central Nervous System: combined model in dog • Respiratory System: Whole body plethysmography in rat or measurements of hemoglobin oxygen saturation • Biomarkers identification, analytical validation and qualification by means of standard and special clinical pathology •G astro Intestinal Tract: intestinal transit time by charcoal meal, gastric emptying by non-invasive bioluminescence imaging • TEM (Transmission Electron Microscopy) and ESEM (Environmental Scanning Electron Microscopy) • I nclusion of Safety Pharmacology endpoints into Toxicological studies: CNS and respiratory assessment in rat, cardiovascular (6 leads ECG) by using external telemetry in dog •C omplementary core capabilities include: Bioanalytical, Pharmacokinetics and Drug Metabolism services as well as Immunoassays, Immunogenicity testing and Immunotoxicology assays Genetic Toxicology Core Capabilities • Ames test: standard plate incorporation and pre-incubation assays • Chromosome aberration test: in vitro Human Lymphocytes (HPLA) assay - In vitro and in vivo micronucleus assay • In vitro and in vivo Comet assay APT/FACT/VERONA26/SAFETY/01/14/V001 FACTSHEET Safety Assessment Our dedicated expert team offers the highest standard of service Aptuit’s experienced scientists have proven expertise in integrated preclinical development for small and large molecules as well as viral vectors and Gene Therapy Medicinal Products. They have tailored studies and programs based on specific client needs, maintaining an interdisciplinary attitude and taking a team approach. Our scientists have been involved in a multitude of multidisciplinary “problem solving” studies. Working within a strong regulatory environment, Aptuit scientific teams provide the assurance of client-centered project management; consistent lead times; close working relationships with customers’ Support Services; and, GLP Compliance independent monitoring. It is our uncommon expertise that allows Aptuit to identify the Uncommon expertise. Exceptional results. For information about Aptuit’s services, please contact us: in Europe: +39 045 821 9333 in the US: 855-506-6360 email us at: [email protected] www.aptuit.com Aptuit provides early to mid-phase drug development solutions by applying scientific excellence, outstanding service and a team of some of the foremost scientific professionals in the industry. These drug discovery and development professionals offer proven experience unexpected, mitigating risks and maximizing promising possibilities, ensuring exceptional results through an open, transparent climate of trust that our clients can count on. Aptuit’s comprehensive drug development services include: • • • • • Drug Design & Discovery Preclinical Biosciences API Development & Manufacture Solid State Chemistry Pharmaceutical Sciences • A ptuit INDiGO® - fast track to IND program • Integrated Drug Discovery & Development in key therapeutic areas. They share a legacy of success, having advanced a large number of molecules efficiently, expeditiously and economically, from early discovery through clinical development with low attrition rates. APT/FACT/VERONA26/SAFETY/01/14/V001