Services
Discovery
Discovery services span across multiple therapeutic areas and classes of molecules.
We deliver translational research and contract services for academia and industry.
Our Expertise and Services
We offer a unique portfolio of R&D services in antibody discovery, in vitro and in vivo phage display, antibody engineering, and preclinical PK and efficacy studies.
Our expertise includes the construction of antibody libraries (VL/VH, scFv, Fab), high-throughput screening (e.g., ELISA), recombinant expression and purification, and comprehensive activity profiling.
Beyond antibodies, we also have strong expertise in the preclinical development of small molecules, and recombinant proteins — including pharmacokinetic, efficacy, and mechanism of action (MoA) studies in oncology, infectious diseases, neurodegenerative and ophthalmologic disorders.
Additionally, we also offer customized models for different therapeutic areas and products, including medical devices.
Antibodies
- High throught put free immobilization immunoassays and antibody screening;
- Antibody assessment and engineering (affinity, concentration, kinetics, protein interactions, stability, solubility, humanization, single-domain antibodies-SdAb);
- Mechanism Of Action (FcRn binding assays, ADCC & ADCP assays, agonist/blocking assays, cell reporter assays).
Barrier models
- In vitro Blood Brain Barrier (BBB) drug translocation assays and evaluation of BBB integrity;
- Caco-2 (human colon adenocarcinoma cell line) model to evaluate intestinal barrier drug translocation;
- TEER measurement;
- Determination of Apparent Permeability (Papp) of test compounds in both directions (detection through fluorescence or HPLC).
CAR-T cell therapy
- CAR design, expression;
- CAR function & characterization/assessment;
- CAR activation & specificity;
- CAR cytotoxicity;
- CAR exhaustion.
Immunogenicity
- Anti-drug antibodies (ADA) screening;
- Detection of neutralizing ADA (Nab);
- Drug tolerant assays to detect ADA imune complexes;
- Binding affinity and ADA serum concentration in clinical samples;
- Customized PK assays to support therapeutic drug management;
- Charracterization of ADA response in long-term enzyme replacement therapies.
Infectious diseases
- Evaluation of Minimum Inhibitory (MIC) and Minimimum Bactericidal Concentration (MBC);
- Antiviral drug screening under Biosafety Levels 2 and 3;
- Antiviral activity in tissue-specific cell lines;
- Antiviral activity in textiles and plastics; Custom-tailored assays.
Neuroscience
- Cell cultures, including primary cell cultures, cell lines, organotypic, 3D cell cultures;
- In vivo models, including Alzheimer’s and Parkinson’s diseases, Epilepsy, Multiple Sclerosis, Amyotrophic Lateral Sclerosis;
- Customized models;
- Behavioral and functional assays available, including electrophysiology and preclinical imaging (including MRI, PET, SPECT).
Oncology
- In vitro and in vivo studies in cancer models, including lymphoma, glioblastoma, breast cancer, lung cancer and other customizable models;
- Xenograft models;
- Syngeneic models;
- Metastasis models.
Ophthalmology
- In vitro and in vivo models of injury, inflammation, diabetic retinopathy, glaucoma and age-related macular degeneration;
- Retina cell cultures (including organotypic cell cultures);
- Cell lines from mouse and human (including endotelial, retinal Muller and micro glial cell lines);
- Porcine Corneal explants to assess wound healing;
- Customized models.
Hit to Lead
Hit-to-lead is a process in drug discovery where a potential drug ‘hit’ or lead compound is identified from a large pool of chemical compounds or natural product extracts that have shown activity against a specific target.
The goal of hit-to-lead optimization is to identify a lead compound that has sufficient potency, selectivity and drug-like properties.
This process requires a multidisciplinar approach and often starts with high-throughput screening techniques.
Molecular Biophysics
Protein-protein, solute-solute, solute-lipid interactions
- Absorbance and fluorescence spectroscopy: time-correlated single-photon counting;
- Fluorescence anisotropy (steady-state and time-resolved) surface plasmon resonance;
- Chromatography;
- Fret-melting;
- UV spectroscopy;
- Isothermal titration calorimetry (ITC);
- HTRF Homogeneous Time Resolved Fluorescence (Cisbio);
- AlphaScreen- Amplified Luminescence Proximity Homogeneous Assay;
- Biophysical tools to evaluate antibody affinity, stability and potency;
- Fiber-optic SPR (Fox Biosystems);
- Microfluidic Diffusional Sizing (Fluidic Analytics).
Molecular structure
Protein-protein, solute-solute, solute-lipid interactions
- Circular dichroism spectroscopy;
- Fourier-transform infrared spectroscopy;
- Nuclear Magnetic Resonance (NMR).
Aggregation dynamics
- Dynamic light scattering;
- Absorbance and fluorescence spectroscopy;
- Transmission Electron Microscopy;
- Nanoparticle Tracking Analyser;
- Techniques to evaluate protein stability in forced aggregation assays (MDS; FO-SPR).
Phage Display
Used to screen large libraries of candidate molecules that act on/interact with a specific target.
A gene encoding a protein/peptide of interest is inserted into a phage coat protein gene, causing the phage to “display” the protein on its outside.
These displaying phages can then be screened against other proteins, peptides or DNA sequences, in order to detect interaction between the displayed protein/peptide and those other molecules.
The in vivo phage display consists in the selection of phage libraries using biopannings in living animals.
The phages circulate in the organism allowing the expressed molecules at the phage surface to bind directly to the specific target, organ or tissues.
- Screening of hit (target) binders (leads);
- Selection of tissue specific leads (peptides/antibodies);
- Selection of target specific moieties;
- Construction of phage display libraries;
- Optimization of protocols;
- Isolation and identification of targeting phage displayed binders;
- Enrichment screening for specific targets through several rounds;
- Identification of organ specific moieties;
- Next generation sequencing (NGS) of the selected ligands/leads.
Cellular and Tissue Biophysics
Cellular morphology and biomechanics
- Atomic force microscopy;
- Transmission electron microscopy.
Cellular membrane penetration
- Fluorescence spectroscopy;
- Flow cytometry;
- Confocal microscopy.
Computational methods
- Algorithms and machine learning;
- Molecular docking;
- Molecular dynamics simulations.
In vitro Blood Brain Barrier (BBB) permeability evaluation
This assay is often used to screen hit compounds for the treatment of neurological diseases, of CNS tumors and brain metastasis, and of infectious diseases (e.g. SARS-CoV-2, HIV, etc).
It is used to evaluate drug candidate’s transport across the BBB and their effect on BBB integrity; to evaluate cytotoxicity and morphological alterations of BBB endothelial cells; to study drug transport mechanisms and to identify potential drug off-target effects in the brain.
In vitro models
- Human (HBEC-5i) or mouse (bEnd.3) BBB models using confluent cell monolayers cultured in permeable tissue culture inserts (monoculture or co-culture with brain vascular pericytes).
Outputs
- Evaluation of markers of BBB integrity: Lucifer Yellow, FD4 or FD40;
- Transepithelial Electrical Resistance (TEER) readings;
- Determination of compounds concentration: fluorescence intensity measurement or reversed phase HPLC;
- Determination of Apparent Permeability (Papp) of test compounds in both directions.
In vitro Intestinal permeability evaluation
The study of the transport of drug candidates and other molecules across the intestinal epithelium is essential to predict their bioavailability in humans. Caco-2 (human colon adenocarcinoma cell line) cell culture model is widely used to that end as it closely resembles the intestinal epithelium in terms of morphology, function and expression of transport enzymes involved in drug absorption and metabolism. Thus, it can be used to predict oral drug absorption in humans, as well as to evaluate drug-drug interactions, toxicity and pharmacokinetics.
Outputs
- Transepithelial Electrical Resistance (TEER) readings;
- Determination of compounds concentration through HPLC;
- Determination of Apparent Permeability (Papp) of test compounds in both directions.
Lead Characterization and Optimization
Lead characterization and optimization is a crucial stage in the drug discovery process where molecules identified as promising candidates to treat different pathological conditions are characterized and optimized in terms of their potency, selectivity, pharmacokinetic properties and safety profile.
Antibodies
- Target identity/validation (High throughput free immobilization immunoassays);
- Antibody engineering (affinity maturation; single-domain antibodies; humanization, solubility and half-life optimization; stability profile);
- Antibody screening using phage display;
- Antibody library construction in several formats (scFv, Fab, sdAbs) and types (imune, naϊve or synthetic);
- Single B cell screening;
- Antibody sequence analysis;
- Functional assays: binding assays; antibody dependent cellular cytotoxicity or phagocytosis assays; agonistic/blocking assays; cell reporter assays.
In vitro ADME-Tox assays
The in vitro assays provide valuable data for deciphering the mechanisms and drug-related determinants underlying the drug candidates’ journey in the body and predicting the in vivo pharmacokinetic (PK) and pharmacodynamics (PD) profiles.
In vivo pharmacokinetic assays (in rodents)
In vivo PK studies, compounds are administered to rodents and samples collected over a pre-defined time period. The dosing regimen and sampling are designed according to the project needs and prior information available on the study compounds.
Services
- Single or repeated dosing (i.p., i.v., p.o., s.c., i.m.);
- Studies with small molecules, peptides and proteins;
- Plasma sampling, tissue and CSF collection;
- Bioanalysis by LC/MS/MS or UPLC/High-resolution-MS analysis.
In vitro assays
- Caco-2 Permeability
- BBB permeability (rodents, humans, pigs, dogs)
- Efflux Transporters (substrate and inhibition assays):
A family of ATP binding cassette (ABC) transporters is an important group of membrane transporters involved in drug absorption, distribution and elimination. Regulatory authorities (EMA, FDA) recommend investigating the potential roles of ABC superfamily members ABCB1 (MDR1, P-glycoprotein), and ABCG2 (BCRP) for transporter-mediated drug-drug interactions (DDI), by evaluating whether the new drug candidate is a substrate (potential DDI victim) or an inhibitor (potential DDI perpetrator) towards drug transporters. Additionally, evaluation of inhibition towards bile salt export pump (BSEP, ABCB11) is recommended due to safety concerns associated with inhibition of this transporter
- Uptake Transporters (substrate and inhibition assays):
A family of solute carriers (SLC) is an important group of membrane transporters involved in drug absorption, distribution and elimination. Regulatory authorities (EMA, FDA) recommend investigating the potential roles of SLC superfamily members OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 and MATE2 for transporter-mediated drug-drug interactions (DDI), by evaluating whether the new drug candidate is a substrate (potential DDI victim) or an inhibitor (potential DDI perpetrator) towards drug transporters. In addition, EMA suggests also considering investigation of OCT1, whenever in vitro and in vivo findings suggest its involvement in DDI to be anticipated
