Your Drug Discovery Partner We make it simple.Enjoy our quality with confidence.

Fidelta is a fully integrated CRO offering a broad range of services and solutions in drug discovery research.

TARGET SELECTION HIT FINDING PRE-CLINICALDEVELOPMENT

PHASE 1 ONWARDSH2L LO

FAST FOLLOWER STRATEGY

PHENOTYPIC SCREENING

NON-GLP TOX

SOLID STATE

BESPOKE TARGET

VALIDATIONGLP BIOANALYTICS

EX VIVO ANALYSES FOR BIOMARKER

RESEARCH

CHEMISTRY, PHARMACOLOGY, EARLY TOX, ADME/PK AND TRANSLATIONAL SCIENCE

ADME/PK

In vivo pharmacology

Translational research

In vitro pharmacology

Our state-of-the-art R&D facilities and scientific know-how in Medicinal chemistry, ADME/PK, In vitro / In vivo pharmacology and toxicology ensures seamless transition from one activity to the next.

— ABOUT US

100 customers from allover the world

more than

Medicinal chemistry

Fidelta differentiates by placing a strong emphasis on translational research and ex vivo assays that include patient disease-relevant tissues and clinical isolates.

In vivo ADME and pharmacology

Medicinal chemistry

In vitro ADME and pharmacology

Translational research

TARGET VALIDATION

HTS(primary assays)

Human 1° cells

Human tissue samples

PK

In vivo efficacy

GLP/non-GLP

bioanalysis

GLP analysis of clinical

material

Non-GLP toxicology

Assay development

(biochemical & cell-b

ased)

CADD

Library design

Tier 1 ADME

Solid stateEx vivo analyses fo

r biomarker

selection

Tier 2 ADME

Synthetic & Analytical

chemistry

PK/PD

H2L PRE-CLINICAL DEVELOPMENT

PHASE 1 ONWARDS

HIT ID LO

— SUPPORTING OUR PARTNERS IN DRUG DISCOVERY

We work closely with you to:

> define the required compound profile

> design project strategy and optimize the screening cascade

> prioritize compounds for further evaluation

> interpret the results

Our aim is to generate and select high quality lead compound and to avoid progressing compounds which are unlikely to pass development (solubility issues, tox issues etc.)

Scale up & Process

chemistry

— WHY CHOOSE FIDELTA FOR R&D OUTSOURCING?

• Track-record of success

> 75 integrated projects across a broad range of TA> 180 publications and 96 PCT applications in last two decades

• Integrated drug discovery services (FTE of FFS)

• Development of tailor made assays and animal models

• Ex vivo assays on samples from healthy volunteers and patients

PROJECT PHASE

To Hit Finding To Hit to Lead To LeadOp To PCC

of which 6 in the clinic

9282711

Immunooncology 3%

Oncology 16%

Inflammation incl.

Fibrosis 46%

Infection 28%

CNS 4%Other 3%

— OUR HISTORY

Best of both worlds

- big pharma and biotech experience

19522006

20132010

— STATE-OF-THE-ART R&D FACILITIES

Fully equipped with instruments essential for modern and innovative drug discovery and development

> 4000 square meters of laboratory and office space

> 30 laboratories

> 50 fume cupboards

> A scale-up lab

> AAALAC-I and OLAW accredited animal facility

> GLP certified bioanalysis

GLPGood Laboratory

Practice

— SCIENTIFIC TEAM

> 140 highly qualified scientists with an average of 12 years of industry experience each

> Multidisciplinary and high-performing drug discovery teams

> Flexible resource distribution between Chemistry, Pharmacology and DMPK according to

the project needs

— DRUG DISCOVERY CAPABILITIES

FIDELTA OFFERS — Medicinal chemistry

— ADME/PK

— In vitro pharmacology

— In vivo pharmacology

— Translational research

— MEDICINAL CHEMISTRY

ANALYSIS

DESIGN

SYNTHESIS

TESTING

Biochemical/ functional assaysADME and PK profilingAnimal modelsHuman samples

CheminformaticsDevising project strategyProject management

ANALYSIS Structure based drug designLigand based drug designVirtual screeningKnowledge-based design

DESIGN

Custom synthesisSemi-parallel synthesisModern technologies (MW, flow)Scale up & Process chemistry (up to 1 kg)

SYNTHESIS

TESTING

MED

ICIN

AL

CHEM

ISTR

Y

• Fully integrated with other Fidelta’s / client’s departments

• Extensive experience in synthesis and development of small molecules and macrocycles

• In-depth knowledge of a wide range of target classes; enzymes (protein kinases, epigenetic targets), G protein-coupled receptors, ion channels, protein-protein interactions etc…

We support all aspects of integrated drug discovery from Hit ID to the PCC nomination

DEVELOPMENT / IND SUPPORT

LEAD OPTIMISATION

HIT-TO-LEAD

HIT ID & GENERATION

• Hit confirmation & rapid SAR exploration• Lead generation suitable for LO progression

• Phys-Chem property consideration; e.g. clogP, TPSA, Ro3, Ro5,solubility, LE, LLE

• ADME & PK assessment• FTO and IP assessment

• Innovative drug-like molecular design• Project management & strategy; devising flexible screening cascade• Pharmacology & DMPK evaluation; target engagement, efficacy, PK and safety projections• Support with IP protection / patent filings• Candidate nomination

• Scale-up/Process chemistry; route development & tech transfer packages

• Solid state • 7-Day toxicology studies

• IVIVE / human dose projections• GLP bioanalysis

• In Silico screening• Macrocyclic libraries for challenging targets• Knowledge-based design• HTS output evaluation • Scaffold hopping

MED

ICIN

AL

CHEM

ISTR

Y

COMPUTER-AIDED DRUG DESIGN (CADD)

SYNTHETIC CHEMISTRY CAPABILITIES

Structure based drug designLigand based drug designCheminformaticsExpertize in macrocycles

Custom synthesis

Modern synthetic transformations and functional group inter-conversions

Contemporary methods and techniques related to synthesis, isolation and identification (microwave and flow assisted synthesis)

Synthesis by request, including development and optimisation of synthetic pathways

Multistep synthesis service (>10 steps) of milligram quantities

Validation of synthetic routes to previously unknown scaffolds

Semi-parallel synthesis

Focused arrays of discrete compounds up to 100 NCEs

— MED-CHEM SERVICESSCALE UP & PROCESS

CHEMISTYRapid transfer from small to large scale (up to 1 kg)

In-process analytical chemistry integrated part of scale up

Non GMP production

Redesign and synthetic routes optimization

Medicinal chemistry is tightly integrated

with CADD, Synthetic, Scale up and

Analytical chemistry

MED

ICIN

AL

CHEM

ISTR

Y

ANALYTICAL CHEMISTRY

NMR structural studies

Structure determination of by-products, impurities, degradation products, unexpected result of chemical reaction

NMR instruments: automated; open-acess

Stability and solubility studies

STABILITY STUDIES: - Solid state (regulatory and ICH conditions): VT, VRH, light stability; - Solution stability: Buffers, bio-relevant media (SGF, FeSSIF, FaSSIF)

SOLUBILITY STUDIES IN VARIOUS MEDIA: Buffers, bio-relevant media, organic solvents

Solid state characterization

XRPD (RT, VT, VT/VRH)

DSC, TGA

Hot stage and optical microscopy

Karl-Fisher

Single crystal X- ray diffraction, SEM, particle size (all subcontracting)

Discovery analytical services

Achiral and chiral purity assessment (LC)

UPLC/HPLC method development and transfer

MS - and UV-directed purifications

Purification of libraries

Isolation of impurities/degradants

Reference substance characterization with Certificate of Analysis or full scientific report

MED

ICIN

AL

CHEM

ISTR

Y

— DRUG METABOLISM AND PHARMACOKINETICS

We offer comprehensive in vitro ADME assays, pharmacokinetic studies and bioanalytical services including GLP and non-GLP to support medicinal chemistry programs.

All studies are performed in line with SOPs to ensure quality, rapid turnover and efficient service.

AD

ME/

PK

— IN

VIT

RO

AD

ME

PLA

TFO

RM PHYSCHEM

PERMEABILITY

BINDING

METABOLIC STABILITY

DDI

METABOLITE PROFILING & ID

Kinetic solubilityThermodynamic solubility- pH, SGF, FeSSIF, FaSSIFChromLogDChemical stability

Cellular permeabilityMDCK MDCK-MDR1Caco-2

Plasma protein bindingBlood partitioningTissue bindingMicrosomal binding

Microsomes, S9, HepatocytesRecombinant enzymesPlasma and bloodSGF, FeSSIF

InhibitionCYP450 direct inhibition & MDI (recombinant, HLM)Reactive metabolitesGlutathione trapping

Aldehyde Oxidase reactionPhenotypingMetabolite identificationInterspecies profiling A

DM

E/P

K

— FL

EXIB

LE IN

VIV

O P

K S

TUD

Y D

ESIG

NS ROUTES OF

ADMINISTRATION

SAMPLING METHODS

SAMPLE TYPES

TYPES OF STUDIES

Intravenous, oralsubcutaneous, intraperitoneal, intramuscular, intradermal, topicalintranasal, intratrachealintracolonic

Serial samplingTail- vein, saphenous veinCatheter (jugular, femoral)Heart puncture (terminal)

Whole blood, plasma, serumTissues/organsExcreta (urine, feces)Cerebrospinal fluid (rat)

Rapid screening studies to assess exposurePK studies to estimate disposition kinetics and bioavailabilityDose proportionalityRoutes of excretion (metabolic cages)Customized studies (CSF sampling, intestinal loops)Single and repeated dosing

— BIOANALYTICAL CAPABILITES

Sample analysis are in compliance with internal SOPs and in-line with regulatory bioanalytical guidelines and white papers.

GLP BIOANALYSIS

NON-GLP BIOANALYSIS

Method development and validation

Sample analysis from GLP toxicology studies and clinical studies

Successful GLP inspection in 2017

High throughput bioanalysis to support in vitro ADME screening

Metabolite ID and reactive metabolite screening

Method development for preclinical PK, PD and TK studies

Biomarkers

GLPGood Laboratory

Practice

AD

ME/

PK

— IN VITRO PHARMACOLOGY

Fidelta biology team has extensive experience in developing biochemical and cell based assays to support hit and lead identification and optimization.

TARGET VALIDATION

BIOCHEMICAL ASSAYS

TRANSLATIONAL RESEARCH

• Expression in healthy and diseased tissue- qRT-PCR or western blot• Knock-down or overexpression- siRNA and antisense oligonucleotides- Adenoviral and lentiviral transduction

• Broad target experience- GPCRs, nuclear receptors, ion channels, epigenetic targets, kinases, peptidases, hydrolases, other enzymes, transporters, etc • Various readouts - Fluorescence, luminescence, TRF, absorbance, alphaLISA

CELL BASED ASSAYS

• Disease relevant assays in human primary cells- Cells from healthy volunteers or patients- Mediator release- Cell surface and intracellular markers expression- Proliferation- Chemotaxis

• In vitro assays on human tissue samples (healthy donors and patients)• Ex vivo analyses for biomarker selection

IN V

ITR

O P

HA

RM

ACO

LOG

Y

ONCOLOGY

• Target validation- Expression in diseased tissue- Silencing or overexpression

• Cell proliferation- 2D- 3D

INFLAMMATION

• Disease relevant assays in human primary cells and tissues

• Indications in focus:- Fibrosis- Respiratory- Gastrointestinal - RA

— THERAPEUTIC AREAS

IN V

ITR

O P

HA

RM

ACO

LOG

Y

INFECTION

• Bacteria- In house strain collection- Access to clinically relevant pathogens- Antimicrobial susceptibility testing - Compound profiling ∙ resistance development propensity∙ time-kill∙ biofilm studies • Viruses- Rhinovirus and influenza virus- Antiviral activity IMMUNO - ONCOLOGY

• Immune checkpoints

HOST-PATHOGEN INTERACTIONS

• Modulation of host response to viral infection

Fidelta pharmacology team is experienced in using animal models as an irreplaceable tool for a wide range of applications.

IN V

IVO

PH

AR

MA

COLO

GY

— ANIMAL MODELS/THERAPEUTIC AREAS

INFECTION • Bacterial• Viral

FIBROSIS

INFLAMMATION

• Respiratory• IBD• RA• Dermatology

• Pulmonary• Renal• Liver

• >60 animal disease models characterized and validated against clinically relevant pharmacological standards

- Full packages of validation data available

• Flexible usage

- Target validation

- Efficacy testing

- PK/PD relationship

- Mechanistic studies

- Translational studies

- Safety read-outs

IN V

IVO

PH

AR

MA

COLO

GY

— COMPREHENSIVE IN VIVO PROFILING

CLINICAL PATHOLOGY

• Clinical biochemistry• Haematology • Coagulation • ImmunochemistryTAILORED STUDY

DESIGN

• Local and systemic routes of administration• Osmotic pump delivery• Clinical read-outs • Functional read-outs• Biomarkers• Safety read-outs

HISTOPATHOLOGY

• Automated tissue processing• Standard & special staining• IHC/IF and double staining• In situ hybridization (single/double)• Morphometry• Frozen sectioning • Quantitative digital image analysis• Slide scanning IN

VIV

O P

HA

RM

ACO

LOG

Y

TARGET EXPRESSION

COMPOUND TESTING

PHASE I EFFICACY

• Expertise and track record in integrated drug discovery and development up to Phase II• Experience with clinical studies, human sample collection and analysis

TRA

NSL

ATI

ON

AL

RES

EAR

CH

— TRANSLATIONAL RESEARCH AND PATIENT SAMPLE STUDIES

— ETHICAL AND REGULATORY COMPLIANCE

• High quality ethically obtained human tissues from consented patients

• Procedures harmonized with international legislature

› The Human Tissue Act 2004, EU laws and regulations, etc.

• SOP-s covering human sample collection and management

• GCP compliance

TRA

NSL

ATI

ON

AL

RES

EAR

CH

Protocoland ICF

PI selection

Ethics committee approval & contract with the clinical site

Patient recruitment & sample collection

Sample shipment

Sample analysis

CLIENT

CONTACT

Fidelta d.o.o.Prilaz baruna Filipovića 2910000 Zagreb, Croatia

P. +385 1 888 63 00E. fidelta@fidelta.euW. www.fidelta.eu