Pharmacological and Preclinical Development is a fundamental and complex phase of the R&D of new drugs. This phase, which precedes clinical trials on humans, is crucial to determine whether a new chemical compound, a new antibody or an innovative therapy has the necessary conditions to be considered a potential safe and effective drug. During this phase, research focuses on identifying and selecting promising molecules, on evaluating their pharmacological properties and on determining their safety through a number of accurate tests.

The primary goal of preclinical development is twofold: on the one hand, it aims at understanding how the drug candidate interacts with biological systems, and on the other, to ensure that it does not cause unacceptable side effects that could prevent its use in humans. These studies are crucial in order to minimize the risks when the drug moves to the next phases of clinical development, where it will be administered for the first time to human volunteers.

During the preclinical development, studies in animal models and in vitro systems are conducted in order to get detailed data on the pharmacokinetic and pharmacodynamic properties of the compound, such as absorption, distribution, metabolism and excretion (ADME), as well as on its potential toxicity. At the same time, there is an attempt to optimize the drug structure, its formulation, and the production of quality-controlled batches for further testing.

This phase is also characterized by an intensive activity of documentation and preparation for interacting with regulatory authorities, such as the Food and Drug Administration (FDA) in the United States or the European Medicines Agency (EMA) in Europe. The data generated during the preclinical development provide the scientific basis for applying in order to get the authorization to start clinical trials. Therefore, they are crucially important for the success of the entire drug development process.

In summary, Pharmacological and Preclinical Development is a strategic and scientifically rigorous stage which is the bridge between the discovery of new molecules and their possible clinical application, with the ultimate goal of introducing new safe and effective drugs into the market in order to improve human health.

In general, the activities are conducted both in addressing, if required, and/or in defining the sequence of experimental steps necessary to assess both the efficacy (identification of the most appropriate models) and the tolerability of the new pharmacological approach.

In particular, this phase includes a series of studies and tests aimed at ensuring that a new molecule has the potential to become a safe and effective drug for human use.

The different activities planned with the Experiment Sponsor will then be conducted in the different Biogem laboratories including the GLP Test Facility for regulatory studies.

Depending on the state of knowledge acquired or to be acquired from the new putative drug, Biogem may conduct studies in order to:

Identify new compounds

• Screeningthrough tests on large cell libraries for the identification of chemical or biological compounds that can interact with the therapeutic target.
• Structure-Activity Relationship Studies (SAR): Examination of the relationships between the structure of compounds and their biological activity, in order to identify the most promising structure.

Preclinical Efficacy Studies

• In Vitro Efficacy Studies: Experiments on human or animal cells or tissues to test the ability of the drug to modulate the therapeutic target.
• Animal Models of Disease: Use of animal models that reproduce the characteristics of the human disease to evaluate the therapeutic efficacy of the drug.

Pharmacokinetics and Pharmacodynamics tests (PK/PD, GLP Test Facility and Unit for Protein Production)

• Absorption, Distribution, Metabolism and Excretion (ADME): Studies that aim to evaluate the absorption of molecules (small molecules or biological therapies), how they are distributed in tissues, and how they are metabolized and eliminated. This includes in vitro and in vivo experiments to understand the behavior of the drug in the body.
• Pharmacodynamic Studies: Evaluation of the biological effects of the drug and of the relationship between the concentration of the drug and its efficacy.

Preclinical Toxicology (Regulatory Studies, Test Facility)

• Acute and Chronic Toxicity: Evaluation of the toxic effects of single and repeated doses of the drug in animal models over short and long periods.
• Genotoxicity and Carcinogenicity Studies: Tests to determine whether the drug can cause genetic mutations or promote the development of tumors.

Depending on the sponsor's requests for preclinical development, it will be possible to evaluate the coordination of the activities to be carried out in outsourcing of:

Production of Material for Clinical Studies

• Large Scale Synthesis: Production of sufficient quantity of the drug to conduct clinical studies, keeping high standards of purity and quality.
• Quality Control: Tests for ensuring that each batch of the produced drug meets the established quality criteria.

Preparation of Documentation for Regulatory Authorities

• Preclinical Study Reports: Preparation of complete files reporting the results of all the conducted preclinical studies, necessary to obtain the authorization to start clinical trials on humans.
• Communication with Regulatory Authorities: Collaboration with regulatory bodies such as the FDA or EMA to make sure that all relevant regulations are respected before moving to the clinical phase.