In vivo pharmacology and toxicology

Selvita’s in vivo team runs individual proof-of-concept studies, tailor-made efficacy studies, in vivo target validation, PK/PD and mechanistic studies, and customized non-GLP toxicity studies. The team is proficient in testing small molecules, therapeutic antibodies, and a variety of vaccine types.

1. Models of infection
There is a range of validated models with Gram positive (i.e. Staphylococcus aureus, Streptococcus pneumoniae) as well as with Gram negative bacteria (i.e. Haemophilus influenzae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii) using clinically relevant isolates or ATCC strains from in-house collection or specifically provided by the customers. The models include: sepsis, thigh infection, respiratory, skin and urinary tract infections.
Viral respiratory infections are represented by fully profiled mouse models of influenza A and B, respiratory syncytial and rhinoviral infections. Clinical endpoints such as respiration score and physiological respiratory dysfunction assessed by lung hyperresponsiveness measurements are complemented with ex vivo outreads such as changes in lung vascular permeability, inflammatory responses, cellular tissue influx, and histopathological evidence of lung tissue injury.

2. Models of inflammation and autoimmune diseases
The models cover broad area of inflammatory conditions including rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and other gastrointestinal disorders, systemic lupus erythematosus (SLE), vitiligo, asthma, chronic obstructive pulmonary disease (COPD), delayed type hypersensitivity (DTH) and psoriasis. Acute models of general inflammation cover diverse pathophysiological mechanisms to serve as screening models for specific targets whilst the disease models enable testing of compounds in a system that closely mimics human disease. Sophisticated translational read-outs such as colonoscopy in gastrointestinal models and pulmonary function tests in respiratory models massively contribute to the predictive value of these models as well as to generation of valuable data packages for the customers. Selvita’s respiratory offering also includes dosing of compounds by the inhalation route using inhalation tower for nose-only delivery of aerosols and dry powders. Those routes of administration can also be used in pharmacokinetic and toxicity studies.
Models of viral exacerbations of asthma and COPD induced by influenza A virus are available as an outstanding platform to investigate different mechanisms potentially active in these multifactorial diseases.

3. Models of fibrosis
Selvita’s in vivo fibrosis package covers pulmonary fibrosis (bleomycin challenge), liver fibrosis (CCl4 challenge) and non-alcoholic steatohepatitis (NASH, CDAHFD induced). The models are validated with approved and experimental mechanisms using a broad range of read-outs such as direct pulmonary function tests (forced manoeuvre system), gene expression, biochemical analyses and histopathological evaluation of collagen content using quantitative digital imaging.

4. Non-GLP toxicity studies
Selvita’s in vivo team offers a non-GLP toxicity testing at high quality standards to discharge in vivo safety liabilities through tailored study design. The team’s broad experience with different targets and mechanisms allows us to deal with unexpected findings or toxicity issues during the course of the research projects. The customers are getting investigative, problem-solving studies with fit-for-purpose, integrated assessment of multiple endpoints (general toxicology, clinical biochemistry, pathology and bioanalysis).

5. Histopathology and clinical biochemistry services
Histopathology and clinical biochemistry services comprise standard and special histological techniques combined with quantitative digital imaging using deep learning software for tissue analysis as well as full panel of automated clinical biochemistry, haematology and coagulation analyses. Highly experienced human and veterinary pathologists ensure accurate characterization of animal models, elucidation of compound effects, and link to clinics.

6. Live imaging in mice and rats
Selvita’s in vivo team offers live optical imaging services (Lago, Spectral Instruments) and currently building the expertise in PET/CT scanning (Molecubes), which is used to follow a real-time disease progression and therapy success.

Facilities
In vivo experiments in Selvita are performed in AAALAC-I accredited, biosafety level 2, State-of-the-Art animal facility. The key equipment includes colonoscopy system, inhalation tower, live imaging platform, pulmonary function testing equipment and stereotaxic equipment. Histopathology and clinical biochemistry laboratories are well equipped to cover a full set of methodologies in those areas: haematology, biochemistry and coagulation analysers, tissue processors, embedding units, microtomes, automated staining systems, slide scanners, microscopes, and digital pathology software.