Lead Optimization

In vivo ADMET profiling

Pharmacokinetics (PK)

PK studies are most useful when performed early in the process of assessing a compound. Evaluation of the kinetics of compound plasma concentrations enables the prediction of physiological characteristics of an administered compound, like distribution, bioavailability, and overall elimination rates. These PK parameters can then be used for prediction of plasma concentrations for a given dose and route, allometric scaling, and other simulations to support the decision making process for subsequent in vivo studies.

At Polyphor no in vivo studies are performed in-house. All such studies are conducted in collaboration with specialized external partners who perform the in-life phase of the study (e.g. oral, intravascular, or subcutaneous dosing).

Once the in-life experimental phase is completed, the compound concentration in diverse matrices (e.g. plasma, organs, and excrements), collected during the study, is determined by Polyphor’s in-house bioanalytic group.

Medicinal chemistry

Strong design and synthesis capabilities are at the heart of the development of Polyphor’s proprietary PEMfinder® and MacroFinder® Technology platforms. Both complementary platforms are based on macrocyclic molecules which are ideally suited to address challenging targets involving extra- and intracellular PPIs (protein-protein-interactions). The fully modular and highly automated synthetic process allows for rapid iterative cycles of design, synthesis and biological profiling of MacroFinder® and PEMfinder® libraries to efficiently optimize PK/PD properties of lead molecules. Medicinal chemistry at Polyphor is supported by a comprehensive set of state of the art internal drug discovery capabilities.

Pharmacological profiling PK/PD

Preclinical pharmacology studies are performed in order to pinpoint the therapeutic value of a new drug entity on a specific disease.

In a first step, Polyphor’s pharmacological profiling focuses on in vitro assays:

In vitro pharmacological assays cover a broad range of targets including receptors, ion channels, transporters, enzymes and intracellular signaling pathways. These assays are used to identify lead compounds, to characterize the level of ortholog potency, to define mechanisms of action, and also to identify potential off-target activities giving an initial indication on safety.

In a second step, Polyphor’s pharmacological profiling focuses on in vivo assays:

In vivo pharmacological studies are the basis and main objective of preclinical pharmacology. These studies are performed in order to investigate the efficacy of a new drug entity in pathological conditions on a specific disease.

Efficacy studies are performed in several relevant and validated animal disease models that mimic the pathological signs and symptoms in humans for a given disease. The compound under investigation is administered by different routes at several doses and a dose-response correlation is sought. To get further information about how to assess pharmacokinetics and the assessment of pharmacodynamic effects please see this PDF.