Early Drug Development (eBook)

Fabrizio Giordanetto graduated in Medicinal Chemistry (Genoa, Italy) followed by his Ph.D. (London, UK) while working for the chemistry unit of Pharmacia - Pfizer (Italy). After positions at AstraZeneca (Sweden) as Principal Scientist and Project Leader and at Taros (Germany) as Head of Medicinal Chemistry, he has recently joined DE Shaw Research LLC (New York, USA) where he leads medicinal chemistry activities and drug discovery projects. During his career, he worked on several drug discovery programs resulting in multiple clinical candidates spanning oncology, CNS, inflammation, metabolic and cardiovascular indications and >100 international patents, peer-reviewed publications and book chapters.

Introduction to Early Drug Development

PART I: Drug Substance
Early Phase API Process Development Overview
The Discovery-Development API Transition
API Cost of Goods: Discovery to Early Development
New technologies in Process Development
Case Study: Vortioxetine and Early Drug Development Considerations at the Interface of R&D
Case study: Development of a Practical Synthesis of 4'-Azido-2'beta-Methyl-2'-Desoxycytosine and Its Prodrugs as HCV Chemotherapeutic Agents

PART II: Drug Product
Solubility, Permeability, and their Interplay
Drug Products: Solid-State Properties
Salt and Cocrystal Screening
Particle Size Reduction-From Microsizing to Nanosizing
Drug Product Formulation
A Practical Guide for the Preparation of Drug Nanosuspensions for Preclinical and Early Drug Development Studies

PART III: Pharmacokinetics and Pharmacodynamics
Integration of Pharmacokinetic and Pharmacodynamic Reasoning and Its Importance in Early Drug Development
Prediction of Human Pharmacokinetics and Pharmacodynamics
Translational Modeling and Simulation for Molecularly Targeted Small Molecule Anticancer Agents: Case Studies of Multiple Tyrosine Kinase Inhibitors, Crizotinib and Lorlatinib
Informing Decisions in Discovery and Early Development Research Through Quantitative and Translational Modeling

PART IV: Toxicology
Pre-clinical Toxicology Evaluation
Non-clinical Safety Pharmacology
Predictive Computational Toxicology
Addressing Genotoxicity Risk: A PDE10A Inhibitor Case Study
The Integrated Optimisation of Safety and DMPK Properties Enabling Preclinical Development: A Case History with S1P1 Agonists
From TRAIL to ONC201: Case Study on the Safety Benefit of Developing Targeted Agents Against Cancer-Selective Pathways

PART V: Intellectual Property
Patent Law Relevant to Early Drug Development
Patent Protection Strategy
The Patent Landscape Viewed from Generic and Originator Perspectives
Patent Considerations in Collaborative Drug Development