Pre-Clinical Development of P2B001
P2B001 was discovered after intensive screening of various drugs with dofferent mechanism of action, aimed to identify drugs that complement each others action and work in synergy. Once identified, P2B001 was researched intensively to explore its saftety and effectiveness, and to determine the optimal doses and formulation.
- A remarkable synergy between the drugs as demonstrated in preclinical studies using two independent models. The combination showed a notable pharmacological advantage with no toxicity. Te unique ratio between component doses let to maximum synergy, as demonstrated in figure 1. In addition, development of optimal release profile led to increase the time of mutual action of the components resulting in further increase efficacy. (figure 2).
Figure 1. P2B001 efficacy in mouse MPTP Parkinson's Disease model. Dopamine level in animal brains was used as endpoint. Dose selection was optimized such that treatment with A and B led to a combination effect which was greater than the effect of the sum of the components.
- The optimal release profile enhances the clinical effect by more than 50%, by increasing the time that the component can act in synergy. This is exemplified in figure 2, where two methods of drug application were compared; Immediate Release (IR) versus Sustained Release (SR), with a significant favorable effect shown by the sunatined release formulation.
Figure 2. Comparing P2B001 effect on striatum dopamine level between immediate and sustained release drug administration, in mouse MPTP Parkinson model.