PAN-811: A MULTIFUNCTIONAL NEUROPROTECTANT

Panacea's acute neuronal injury or hypoxia program is designed to identify and select candidate neuroprotective compounds that demonstrate efficacy in proprietary in vitro and in vivo models, and subsequently advance these through human clinical trials.

PAN-811 belongs to a class of molecules that was originally developed for the treatment of cancer. These compounds are efficient chelators of metal ions and potent quenchers of free radicals. Scientists at the Company hypothesized, based on the chemical structure and known functions of PAN-811, that it might also serve as a potent neuroprotectant by inhibiting the neurodegenerative signaling cascade at multiple points. Both the accumulation of intracellular Ca2⁺⁺ and the production of free radicals are pivotal steps in the neurodegenerative process and play major roles in the ensuing cellular damage that precedes neuronal death. PAN-811 as an efficient chelator of metal ions and quencher of free radicals was thus postulated to have great potential as a neuroprotective agent.

Panacea has demonstrated the high efficacy and low neurotoxicity of PAN-811 in several in vitro models of neurodegeneration. Key findings include:

• PAN-811 completely blocks neuronal cell death in vitro under stroke-like (ischemic) conditions
• PAN-811 is more efficacious and has broader utility than other neuroprotectants including NMDA receptor antagonists (e.g. MK-801 & memantine) and anti-oxidants (e.g. vitamin E & lipoic acid).
• PAN-811 is most efficacious when delivered during, and especially after, ischemic assault indicating its potential for use subsequent to initiation of the neurodegenerative cascade.
• PAN-811 protects cells from multiple insults that initiate neurodegeneration at various points along the neurodegenerative cascade including ischemia, hypoxia, NMDA receptor agonists, sodium channel blockers, inducers of apoptosis and oxidative stress.