Drug Discovery

Selvita provides its clients with effective drug discovery support based on broad capabilities and deep experience in small molecule drug discovery, starting from target validation up to the selection of a clinical candidate. We powerfully execute fully-integrated drug discovery programs combining all of Selvita’s core skills in biology and chemistry or else provide partially-integrated or stand-alone services utilising selected capabilities optimally matched to the specific needs of our clients.

Selvita is built on robust capabilities and experience in assay development and screening, medicinal and synthetic chemistry, computer-aided drug design, structural biology, in vitro pharmacology, ADME/DMPK and analytical testing. In collaboration with proven and experienced partners, we also offer pharmacological and efficacy testing with in vivo models of disease available for variety of indications. Our daughter company, Ardigen, supports us in increasing the speed and reducing the cost of drug discovery process by using Artificial Intelligence tools.

Selvita has already proven its impact on the global innovation. Through a great number of projects executed for over 10 years, we have contributed to impactful discoveries in various areas. Our scientific team have built strong partnerships and become an integral part of our clients’ organizations ensuring out-of-the-box thinking, strong IP protection and goal achievement.
    icon Regulatory Studies Integrated Drug Discovery
  • Assay development & screening

    Selvita offers custom assay development and screening/profiling services up to 1536-well plate format.

    Our team is built on extensive expertise in the areas of molecular biology, biochemistry, immunology and cell biology. We have a track of record in assay development for various classes of targets, including enzymes (kinases, phosphatases, metabolic enzymes, immuno-modulatory enzymes) and protein receptors (GPCRs, nuclear receptors). Selvita’s state of art-equipment allows for a wide variety of detection modes to be implemented, adding value to your drug discovery program.

    Biochemical and cell-based assays
    Supported readouts:

    • Absorbance and Fluorescence (endpoint, kinetic)
    • Fluorescence Resonance Energy Transfer (FRET) and Time -Resolved FRET (TR FRET)
    • Fluorescence Polarization (FP)
    • Luminescence
    • Scintillation counting (3H and 14C)
    • Cell based reporter & viability assays
    • AlphaScreen bead-based proximity assays
    Biophysical assays
    • Surface plasmon resonance (SPR)
    • Thermal shift (differential scanning fluorimetry)
    • Microscale thermophoresis (MST)
    • Isothermal titration calorimetry (ITC)

    Selvita can offer case-by-case selection of suitable cellular model/s to investigate the biological mechanism of interest (e.g. cancer cell panels of a specific type and/or with common mutation patterns). Our in-house capabilities for reagent generation include in-house production and validation of recombinant cell lines and recombinant proteins. Our assay development strategies are characterized by efficient and effective protocols. Usually, multi-factor design of experiments is employed during method development.  It accelerates optimization of the assay performance, thus helping to obtain a measurement system that meets its requirements. Statistical parameters are used to support a reliable and robust assay for routine use, e.g. IC50/EC50; mRSD (mean Relative Standard Deviation); S/N ratio; Z’ factor; plate uniformity.

  • Medicinal Synthetic Chemistry

    Medicinal chemistry is an interdisciplinary science which plays a crucial role in the drug discovery process. In medicinal chemistry we follow a highly data-and-hypothesis driven path making meaningful molecules whilst also using productive synthetic routes to bring benefit both from efficiency and from serendipitous discoveries.

    We are skilled at multi-parameter optimisation based on the analysis of biological, structural and physicochemical data. We use these expanding data sets from ADME assessments, computer-aided drug design, structural biology, in vitro and in vivo biological testing, and disease models to refine our thinking and to influence the design of new iterations of molecules. In addition, the effectiveness with which the projects are executed is very dependent on the quality of the infrastructure but even more by the quality and passion of our people.

    We benefit from close interactions with colleagues in the associated scientific disciplines and execute our work together under one roof in our drug discovery facilities in Krakow. Our skill in chemistry is built on years of diverse experience in small molecule synthesis and incorporates strengths in the efficient preparation of compounds across multiple chemotypes including heterocyclic synthesis, macrocyclics, peptidic molecules, steroids and nucleosides, and beyond. Our strong asset is “out-of-box” thinking and application of the latest techniques like flow-, electro- and photochemistry where classical methods reached their boundaries.

  • In Vitro / In Vivo Pharmacology

    The biology offering at Selvita covers all drug discovery purposes from target validation through to preclinical candidate selection. We provide a protein-to cell approach for the development of pharmacologically active compounds.

    Our in vitro pharmacology activities commence from the customized production of recombinant proteins for use as screening proteins to probe compound interaction in a panel of biochemical and biophysical methods, also in a high-throughput screening mode. In parallel, using Selvita’s considerable internal experience of protein crystallization, protein structural analyses can be performed by X-ray. Using cell-based assays, we perform small molecule activity analysis using of a large repository of cells.

    These cell-based assays can also be run in a high-throughput screening mode for hit finding. Close to two hundred recombinant cell lines are available for assay development, adaptable to many pathological areas. Selvita offers the custom production of recombinant cell lines expressing the protein target of interest. In addition, primary cells, for example from human (blood) or from rodent (CNS), are available upon request for assay development. Secondary screening for pharmacological evaluation of compound characteristics is part of our Integrated Drug Discovery expertise. Mode of action, biomarkers, target engagement studies are provided for hit characterization, and for lead finding and optimization.

    Multiple readouts are available from classical fluorescence, interference (TR-FRET) or biochemical-based up to bioluminescence gene reporter assays or Alpha-Lisa technology, from medium throughput to HTS, and up to 1536 well plates depending on the scalability of the assays. In vivo evaluations can be arranged by Selvita during the lead optimisation and prior to preclinical development candidate selection. We analyse tissue samples, generate and interpret PK parameters or drug and biomarker concentration for pharmacodynamic studies in many disease areas such as cancer and CNS.

  • ADME/PK

    Selvita offers a standard panel of in vitro ADME assays, which can be customized to fit client requirements, and provides comprehensive bioanalytical support based on our mass spectrometry platform. Our mission is to successfully support our Clients along the drug development pathway, to deliver high quality results provided by our experienced ADME specialists using state-of-the-art technologies. We provide fast turnaround times and maximum flexibility to deliver fit-for-purpose studies and achieve the specific goals of our client projects. ADME studies are offered either as stand-alone projects (fee for service model) or as a part of a collaborative Integrated Drug Discovery (IDD) program. In both cases, SLV provides a flexible approach by customizable protocols, which covers a very wide range of different needs. In addition, Selvita can propose a panel of ADME and Pharmacokinetic parameters analysis in a preassembled package which can be easily changed and customizable. The panel is ideally divided into a tiered approach depending on the drug discovery phases and then used for filtering and optimizing the ADME properties of compounds in a SAR fashion. Selvita will provide the full or partial ADME/PK package and also variants (e.g. urine analysis, tissues stability and others) following Client requests or project team decisions. Eventually, Selvita’s ADME/PK expert analysts can suggest the best compounds to be progressed into LO phase and in vivo PD experiments. Our Bioanalytical capabilities cover analyses of small molecules supporting both non-GLP as well as GLP- studies including a wide range of different activities from simple qualitative analyses to complex validation of analytical methods. Selvita also has broad experience with different sample preparation approaches using biological materials.

    ADME tests:

    Physico-Chemical Profiling

    • Kinetic Solubility
    • Thermodynamic Solubility
    • Lipophilicity (LogD/LogP)
    • pKa determination In vitro Permeability Studies Passive Transport Assessment
    • PAMPA GI • PAMPA BBB Active Transport Assessment • Caco-2 Permeability
    • MDR1-MDCKII Permeability In vitro Metabolism Studies
    • Microsomal stability
    • S9 Stability
    • Hepatocyte Stability
    • Plasma Stability
    • Metabolite Profiling and Identification

    In vitro Binding Studies:

    • Plasma Protein Binding – Rapid Equilibrium Dialysis
    • Plasma Protein Binding – High Sensitivity Binding Kit
    • Tissue Binding – Rapid Equilibrium Dialysis CYP Studies
    • Inhibition of the cytochrome P450 isoform activity (IC50, screening assay)

    Bioanalytical Capabilities:

    • Method Development/Transfer
    • Method Verification
    • Method Validation
    • Qualitative Analysis
    • Quantitative Analysis Matrices: Plasma and Tissue Homogenates
  • Structural biology

    Department of Biochemistry has long-standing expertise in supporting development of biologically active chemical compounds for multiple pharmaceutical, agrochemical and biotech companies. Extensive know-how combined with highly skilled and goal-oriented scientists is a perfect combination enabling a successful execution of your project.

    Our services are dedicated to assist in multiple steps during the process of active compound development by providing high quality recombinant proteins and comprehensive structural information. Flexible pipelines employed by Selvita ensure efficient delivery of tailored protein products for various research purposes including crystallographic, biophysical, enzymatic or in vivo studies. Our X-ray services are designed to provide high-resolution structural information to support hit validation, hit-to-lead development and lead optimization in the most time/cost efficient manner.

     

    Protein Production

    Solid expertise of our scientific team with a broad range of target proteins make a strong basis for meeting Client expectations. Our offer includes:

    • coli, insect cell and mammalian expression systems
    • Customized production of target proteins on a mgs to tens of mgs scale
    • Development and optimization of purification protocol to maximize the protein quality (typically >90-95% purity)
    • Tailored protein products (e.g. tags, non-radioactive isotopic labelling – 15N, 13C, low-endotoxin levels)
    • Standard Quality Control evaluating protein concentration, purity, stability, homogeneity and oligomeric status
    • Detailed reports

     

    Macromolecular crystallography

    Structural studies using X-ray crystallography are driven by a team with many years of international experience. Altogether, we have determined 200+ high-resolution structures and published 60+ research papers. Our services include:

    • Screening of 1200+ crystallization conditions using a nanodispensing robotic system
    • Optimization of initial hits, including, but not limited to, grid screening around the primary crystallization conditions and seeding approaches
    • Secured access to synchrotron measurements across Europe
    • X-ray data processing and analysis using XDS and CCP4 packages
    • Structure determination using Molecular Replacement and Experimental Phasing
    • Providing structures of protein-small molecule, protein-protein and protein-nucleic acid complexes
    • Detailed reports
  • CADD/Artificial Intelligence

    Computer-Aided Drug Design Selvita’s computer-aided drug design (CADD) centre was created to foster collaborative research between medicinal chemists, biologists, biophysicists, structural biologists and computational scientists. In a drug discovery campaign, CADD is usually used for three major purposes:

    1. physico-chemical and structural characterization of compounds from various libraries followed by filtering large compound libraries into smaller sets of predicted active compounds that can be tested experimentally;
    2. SAR analysis to guide the optimization of lead compounds, whether to increase its affinity or optimize drug metabolism and pharmacokinetic (DMPK) properties including absorption, distribution, metabolism, excretion, and the potential for toxicity (ADMET);
    3. design novel compounds with a help of a miscellaneous set of computational tools.

    CADD depends on the extent of structure and other information available regarding the target (enzyme/receptor/protein) and the ligands. The latest advancements like AI, QSAR, combinatorial chemistry, different databases and available new software tools provide a basis for designing of ligands and inhibitors that require specificity and novelty. The theoretical basis of CADD involves chemoinformatics, molecular mechanics, quantum mechanics, molecular dynamics, structure-based drug design (SBDD), ligand-based drug design (LBDD), homology modeling, ligplot analysis, molecular docking, de novo drug design, pharmacophore modeling and mapping, virtual screening (VS), quantitative structure-activity relationships (QSARs), in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction. Artificial intelligence (AI) with advanced machine learning techniques plays an important role within CADD tool-box. Most notably, our computational and medicinal chemists are working seamlessly together in interactive molecular design sessions, in order to rapidly generate hypotheses for molecular drug designs that are immediately assessed in suitable in silico models before molecules are prioritized and selected for syntheses in our laboratories or purchasing. Using a diverse set of available computation chemistry tools that are applicable for a given project, we assist the medical chemists in order to minimize the time, synthetic efforts and detours along the transformation process of a hit compound into a candidate.

    AI-driven Drug Discovery

    At Selvita not only we use traditional CADD but we also employ methods based on artificial intelligence (AI) or machine learning (ML). Those methods are especially useful for designing focused screening libraries, as a support in properties optimization process or to predict ADMET properties. Since the main task of the AI-based methods is to find associations between seemingly unrelated data, they are also very useful in target deconvolution process. All tasks related to AI and ML are performed in collaboration with ARDIGEN – SELVITA GROUP company specializing in this area.

Regulatory studies

Being a versatile contract research organization, for over a decade Selvita has been providing also world-class pharma services in the field of drug testing and bioanalytical analyses. We offer services at every stage of the drug discovery process, from development and validation of methods, stability studies, to routine quality control testing.

The quality of our services has been repeatedly confirmed during the GMP and GLP inspections. Obtained GMP and GLP certificates additionally prove that services provided by Selvita are performed in accordance with the highest standards of the pharmaceutical industry, and cover all services offered by our laboratories.

We are located in Krakow having a total area of 4,000 m² (laboratory and office spaces) of which approximately 800 m² are GxP-certified laboratory spaces. The GxP spaces are divided between two departments: cell and molecular biology and analytical laboratories. Both departments provide analytical services to the pharmaceutical industry, especially in the quality control area. In addition to being equipped with state-of-the-art analytical devices, the cell and molecular biology laboratory works under the biosafety level 2 regime. All laboratory activities are conducted under Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) and according to valid ICH guidelines.
  • Development and optimization

    Development and optimization phases during the drug life cycle are crucial. We’re fully aware of that fact, and we work in an efficient and flexible manner, using the best industry practices, in order to support our clients at this important stage of the process. Our team consist of industry experts with a thorough understanding of the process and long-standing expertise in the field, complemented with appreciation of the latest trends in analytical and bioanalytical chemistry.

    At this stage we develop and test new analytical and bioanalytical methods. When do we develop a new method? We usually do this in several cases: when the existing method described in the guidelines is obsolete or does not meet the clients’ requirements; for new medicinal product when there is no efficient method for purity determination or assay; when the final product is a mixture of different active ingredients.

    For method development we use either HPLC or UHPLC. Our analytical department is equipped with liquid chromatographs Agilent 1260 Infinity II and 1290 Infinity II (Agilent Technologies), Ultimate 3000 RS UHPLC and Ultimate 3000 SD HPLC (ThermoFisher Scientific) with DAD-UV, PDA, FLD, CAD, ELSD detectors.

  • Validation and transfer

    Once the method is developed and optimized it can be validated, which is mandatory if the method will be potentially used for testing of a drug product. The implementation of a new method to the analytical laboratory is crucial in the method life cycle and is therefore under supervision of the laboratory management and quality assurance unit.

    Validation is always conducted according to approved protocols which can be prepared either according to Selvita’s standard operating procedures (SOPs) or client’s SOPs. When the validation is complete, all results are described in the validation report which then should be approved by the client. The process of transferring a method from the company to another laboratory is also closely supervised. Transfers and validations of the methods are conducted in accordance with the current GMP regulations and approved protocols.

    All the experiments required for these operations are conducted by our experienced analysts and supervised by the laboratory management. This guarantees that the analytical method works accurately and correctly in any workplace it is implemented.

  • Stability studies

    Selvita offers a comprehensive set of services related to the stability studies for different formulations, drug substances or drug product with different dosage forms. The scope of stability studies offered includes preparation of a stability study protocol, study monitoring and a complete analytical testing needed for particular drug, continuous and summary reporting of stability results.

    The test conditions available on site are: 25°C/60% RH, 30°C/65% RH, 30°C/75% RH and 40°C/75% RH and comply with the ICH requirements. Upon client’s request, we can also conduct stability studies in other conditions in the Binder stability chambers. In addition to stability studies, we also carry out photostability, accelerated stability and forced degradation studies.

    The physical and chemical stresses include especially: exposure to heat, exposure to light (UV/VIS), acidic, alkaline and oxidizing stresses, exposure to elevated temperatures and humidity of the environment. Accelerated stability and forced degradation studies are usually part of development of a new method, but they can also support stability studies for different formulations of a drug product.

  • Quality control

    Quality control is an integral part of the drug production process. Selvita specializes in the final stage of quality control of pharmaceutical products (small and large molecules) – routine analyzes of batches for release (release testing).

    This type of testing is based on the approved specification of the drug product. Selvita does not have a GMP production line but holds GMP certificate and manufacturing license which allow to perform release testing by our GxP laboratories. Selvita also holds the import license which is required for release testing of batches that were produced outside the EU.

    Selvita’s portfolio of methods for release testing is very extensive. We offer the following physico-chemical methods: HPLC, UHPLC, RP-HPLC, SEC, IEX, IF, CE, GC, IEF, LC/MS, SDS-PAGE, AAS, ICP-OES, ICP-MS, disintegration time, dissolution, and also biological methods: microbiology testing: sterility, purity, endotoxins, cell culture based bioassays: proliferation assays based on different read-outs, ADCC, CDC, apoptosis assays, reporter gene assays, potency assays. We are proud to be the EU release testing laboratory for the world’s largest pharmaceutical manufacturers.

  • Regulatory aspects support

    In addition to laboratory work, Selvita can also support its clients in other areas. Our team of experts can provide our clients with help in many regulatory aspects such as: Chemistry Manufacturing and Controls (CMC) documentation preparation, filling in the quality module in the Common Technical Documentation (CTD), as well as, batch certification (certificates of analysis and certificates of confirmation) confirmed by the Qualified Persons employed by Selvita.

Research & Development

Since its inception in 2007, Selvita has developed into a major research and development organization with a global network of customers. Although drug discovery remains the flagship activity for the company, significant portion of our business is dedicated to a broad range of other research and development activities, particularly the pharma and agrochemical companies.

We have a dedicated Process Research group, which serves a variety of clients ranging from Big Pharma to biotech to manufacturers of generics. Our chemists undertake even the most challenging synthetic projects, regardless of the scale. Within multidisciplinary project teams involving chemists, computational chemists and biologists we are ready to face the challenges of finding compounds with defined biological activity .
  • Process Research

    Process chemistry can be considered as a bridge connecting small, laboratory scale synthesis with industrial scale processes taking place in pharmaceutical, agrochemical, or petroleum, industries. Process chemists take the synthesis from the milligram scale to the manufacturing scale. This may involve several activities:

    • Finding and development of patentable, cost-effective synthetic routes suitable for large-scale use
    • Troubleshooting and improving of existing processes, particularly to reduce their environmental impact
    • Identifying acceptable ranges for all operational parameters
    • Consulting with regard to the safety issues

    Selvita supplies a unique blend of practical knowledge and experience based on numerous success stories Feasibility studies /Route scouting & development Hunt for novel, patentable and cost-effective synthetic routes begins with exploring state of the art through literature and patent searches, which is made possible by our access to world-class chemical databases and online journals. This combined with the experience and creativity of Selvita’s chemists puts us in a unique position to meet our Clients’ expectations.

    The generated ideas are examined by bench chemists and the successful routes move to an advanced stage of development. Process optimization, parameterization and scale-up Process optimization means finding a balance between yield, cost and the number of steps. Reaction yield often depends on a number of parameters such as temperature, pressure, dilution, reagent excess, reaction time, drying method, etc. Parameterization studies determine optimal ranges for all important variables, so that the best set of conditions can be selected for the further scale up studies.

    Further support including in silico studies As part of an integrated service Selvita offers analytical support necessary for both technology transfer to production and product registration (impurity identification, isolation and synthesis, impurity profiling, etc.).

    We can also generate in silico prediction of likely toxicity profile for a compound if needed for registration or regulatory purposes. Technology transfer Technology transfer is an ultimate step of process development at Selvita. Our chemists have experience with several successful transfers to industry. Some of these run now on thousands kilogram scale. During transfer the Client will receive detailed documentation including process description, analytical methods, reports on impurities, and safety issues discussion.

  • Laboratory scale custom synthesis of NCEs

    Selvita offers preparation of active substances for pharmaceutical (both API and NCE) and agrochemical research (AI) on a mg- up to kg-scale. Furthermore, we specialize in synthesis of key intermediates and building blocks, including optically active materials.

  • Industrial chemistry

    Being aware that the chemical industry is undergoing dynamic change under the influence of global competition and constantly changing regulations, we endeavor to translate the knowledge, experience and creativity of our scientists into practical solutions that will meet the criteria of innovation and competitiveness. We are seeking ways to increase the competitiveness of products on the world market, primary by the following means:

    • decreasing the costs of introducing new products onto the market,
    • optimising technological processes,
    • complying with legal standards,
    • improving products in terms of their properties/specifications.

    We approach each project individually and seek a tailored solution, simultaneously ensuring clear, commercial and application-driven criteria for the project’s success. Our strengths are flexibility, integrity, punctuality, and above all an innovative and multifaceted approach to a problem.

  • Services for agrochemical industry

    Selvita is an experienced partner with a good track record of successful R&D projects performed for different Polish and multinational agrochemical companies.

    For companies that produce and register plant protection substances, we offer a scope of services that includes:

    Analytics under GLP/GMP conditions

    • Development and validation of analytical methods
    • 5B studies
    • Impurities profiling and identification
    • Certification of reference materials
    • Product release analysis
    • Stability testing
    • Selected phys-chem studies

    Chemistry

    • Impurities identification and synthesis
    • Metabolites synthesis
    • Elaboration of new synthetic pathways
    • Scale-up and process optimization

    Biology

    • Photo-, muta- and genotoxicity assessment according to OECD guidelines

     

    Using many years of our experience in drug development, we can participate in projects aimed at introducing innovative pesticides to the market offering expertise in the following areas:

    • Computational chemistry
    • Library design and synthesis
    • Recombinant protein production and characterization
    • Structural analysis of proteins and protein-ligand complexes – X-ray crystallography
    • Development and validation of cell-based assays
    • Development and validation of biochemical methods
    • Binding studies and affinity characterization
    • ADME
    • Metabolite identification
  • Other experience

    Selvita employees are also familiar with various aspects of the petrochemical and and heavy organic synthesis, including amongst others:

    • plasticisers
    • solvents
    • plastics
    • fuel composition
    • biosynthesis

    On top of that we offer synthesis of isotopically labelled compounds. We have significant experience in compound labelling with “cold” isotopes such as deuterium, 13C and 15N. We can also establish a synthetic route suitable for labelling with hot isotopes to be executed at another lab.