Scientific Solutions across the Value Chain

Target ID

• Pathway analysis Omics (Gene and protein)
• Knock-in / knockout

Tool Discovery:

• Antibody Library screening
• Hybridoma
• Transgenic mouse
• NCEs

Bioinformatics:

• Sequence analysis
• Screening
• Target
• Engagement

In vitro assays:

• Biochemical
• Orthogonal
• Cellular assay - HTS/HCS Formats
• CDR grafting

In vitro assays:

• Seq optimization
• Cellular
• Mechanistic
• Relevant Off-Target(s)

In vitro ADME assays:

• Protein binding
• Metabolism
• CYP Inhibition/ Induction

Research Operating Plan:

• Assay Priority
• Key studies & critical path

In vivo assays/ studies:

• PK (R/NR)
• PD, PK/PD
• Efficacy testing

Hypothesis:

• Patient Selection

Later Translational:

• PK/PD/Efficacy
• Refinement of patient selection hypothesis
• Biomarkers

Human Dose Projection

• h-PK Projection
• PK/PD/Efficacy data
• Safety/Tox data

Ph1-HV or Patient (as appropriate):

• Exposure
• PD

Drug Substance (DS, aka API)

• Route Scouting
• Scale up
• Manufacture/ Stability

HTS/DEL/ Fragments/ Virtual Screening

• Library Design/ Synthesis/ Maintenance
• Hit Validation, Re-synthesis
• Series qualification, Prioritization

Optimization:

• Biochemistry/Cell Potency
• Selectivity
• Phys/chem properties
• In vitro/ In vivo Tool

Optimization:

• Target Optimal h-Profile
• Candidate Selection
• Backup Strategy

Cell line development:

• Cell line development
• Process and analytical development

Drug Substance (DS, aka API)

• Route scouting
• Scale up
• Manufacture/ Stability

Process Lock-down

• Process characterization
• Method
• Qualification
• MCB and GLP
• Manufacturing

Drug Product (DP)

• Pre-formulation studies
• Ph1 suitable formulation
• Prototype/stability
• Manufacture/ stability
• IND, BA/BE, DDI and Phase 1 clinical trials
• GCP bioanalysis

In vitro Safety:

• hERG
• Ion Channels

Tox-Suitable Formulation (maximize exposure)

DRF Tox (R/NR) Bioanalysis

• GLP Tox (R/NR)
• GLP Bioanalysis

MTD or RP2D (as appropriate)

• Integrative analysis of panomics, multimodal data
• Knowledge graphs
• In silico knock out simulations
• Mechanism of Action
• Target prioritization and early safety assessment

• Gigascale virtual screening
• HTS/DEL triage and expansion
• Chemical space exploration and prioritization
• Antibody humanization in silico screening
• Epitope prediction
• Repertoire selection

• Generative/ structure/ligand/ fragment-based design
• ADMET predictions
• Sequence/ structure-based biologics design
• Affinity improvement

• In silico affinity maturation
• Liabilities assessment
• Reformatting
• Multiparameter Optimization
• Organ Toxicity Assessment HepTox^TM

• PKPD Efficacy/ translational markers
• Developability assessment

• Patient stratification
• Trial design Biomarkers

• Early PK, MTD/ DRF studies, Exploratory Tox

• IND enabling GLP Tox studies: Ames, Chromosomal aberration, Micronucleus tests, Pivotal repeat dose (Rodent and Non-rodent)
• Safety Pharmacology: CNS, Respiratory, CV Telemetry, hERG

• NDA enabling studies: Sub-chronic and Repro-tox studies
• Local Tolerance study
• Chronic and Carcinogenicity study

• Route scouting
• Process safety evaluation
• Scalability

• Fit to purpose Process dev
• Material supply
• Impurity identification
• Enable and scale
• Tox material delivery

• Process dev, robustness and safety study
• Unit operation studies
• Impurity synthesis & characterization
• DS clinical batch supply

• Process DOE, QBD and scale up studies
• Process Risk assessment
• FMEA analysis
• Registration and process validation batches manuf.

• Commercial batches manufactured and packaging

• Pre-formulation
• Salt polymorph screening
• Excipient compatibility

• Solid Oral & Injectable dosage forms
• Enabling formulation technologies

Clinical Supplies for all phases

• FIH formulation for Phase 1/2A
• Final dosage form for Phase 2B/3 and onwards

• Registration and process validation batches manuf.

• Methods for Pre-formulation and Bio-analytical

• Methods for Intermediate, Final DS, DP
• Forced degradation studies
• Solid state characterization

• Phase appropriate method validation for DS & DP (microbial analysis)
• Specifications for DS & DP
• In process and Finished product analysis
• Final batch release with COA
• Reference standard, Impurities, Isolation and characterization

• Robustness of Analytical methods and full validation as per ICH

• Analysis of commercial batches

• Selection of suitable container closure system & packaging

• Development stability studies

• ICH stability for all phases
• Shelf-life estimation
• Re-test extension

• Stability study of registration/ process validation batch

• Stability study of commercial batches

• Human Pharmacology Unit (FIH trials/Phase I/ BE studies)
• Clinical trial services – full solution provider for conducting global clinical trials
• Central lab services
• Regulated bioanalytical lab for small and large molecule
• Translational science for biobanking, clinical biomarker and novel biomarker identification
• Clinical data management, Biostatistics, Medical Writing and Regulatory Affairs

• Biologics developability assessment and liabilities mitigation

• Multimodal models
• Adaptive trial design
• Clinical markers

• Process simulations and digital twins