While Principia’s discovery platform can address many different target classes, our initial focus has been on kinases. Traditionally, kinase inhibition discovery efforts have focused on either irreversible inhibitors or reversible non-covalent inhibitors. Both of these approaches have limitations.
Reversible covalent technology combines the best aspects of both irreversible and reversible non-covalent target inhibition. The covalent bond formed by our technology is further stabilized by additional specific, but weaker scaffold interactions. The covalent bond is durable, but only in the presence of these weaker scaffold interactions. When the weaker bonds break, the covalent bond breaks as well, and the target is no longer bound. Thus reversible covalent target inhibition combines the long duration of action of irreversible inhibition with the selectivity and reversibility of reversible non-covalent inhibition.
Principia’s discovery and development platform comprises a collection of capabilities to expedite the drug discovery and development process. Our suite of tools contains proprietary methods to model reversible covalent interactions, an in-house library of chemistries, and the knowledge of how these chemistries interact with targets. In addition, Principia has developed customized assays, including biochemical, cellular and pharmacodynamic assays. Knowledge gained from these assays allows Principia to optimize residency time and uncouple pharmacodynamics from pharmacokinetics. With Principia’s platform approach, the durability of target inhibition is no longer just a function of drug exposure, but a tunable feature which can be optimized early in the discovery process.
|1.||Superior Product Attributes|
Principia’s proprietary reversible covalent technology produces compounds with superior profiles:
|Long duration of action|
|Potential for chronic dosing|
|2.||Acceleration of the Drug Discovery Process|
Principia can efficiently optimize compounds that bind weakly into drug candidates that have low or sub nanomolar potency and a high degree of selectivity. The path to mature clinical development candidates can therefore be accelerated.
Principia’s technology is applicable across many target classes and therapeutic areas. The technology can also reach targets currently not addressable by traditional discovery methods.