Long term toxicology studies for Posiphen; 6 months in rats and 9 months in dogs Posiphen tartrate is a small molecule of 487.5 molecular weight, with a Log P of 2.22 resulting oral availability and high blood-brain barrier penetrability. It is a translational inhibitor of neurotoxic proteins, APP, tau and ?-synuclein. By inhibiting these proteins, posiphen normalizes axonal transport, lowers inflammation and protects nerve cells from dying. This novel mechanism promises stop or slow the course of neurodegeneration and to give people with cognitive difficulties the possibility of living a healthy and independent live way into old age. In order to study this drug in Alzheimer?s and/or Parkinson?s patients we need long term tox studies in animals. We propose to conduct two animal toxicology studies: a 6 month rat study with 1 month recovery and a 9 month dog study with 1 month recovery. During the study the animals will be monitored for behavior and safety and after the study the organs and the brain will be evaluated for toxicological findings. We have already progressed posiphen through 3 human phase I safety studies and ADCS started a pharmacodynamic SILK phase IIa study in mild to moderate AD patients in summer of 2016. The data from the phase IIa together with the data from the proposed animal tox studies will allow us to enter posiphen into a 2 to 3 year pivotal phase II/III study in AD patients to show efficacy. The Alzheimer?s field has been dominated by approaches that prevent the processing to A? or remove A? in one of its many forms. Posiphen prevents the synthesis of APP and hence of A?. Accordingly the Parkinson?s field uses similar approaches to inhibit levels of ?-synuclein or LRRK. Again posiphen prevents the synthesis of ?-synuclein. By normalizing the levels APP/A?, tau/phopho-tau and ?- synuclein posiphen prevents the formation of toxic products and prevents death of nerve cells. 1
PAR-18-820 Research Narrative ADCS started a pharmacodynamic SILK phase IIa study in mild to moderate AD patients in October of 2016. The data from the phase IIa together with the data from the proposed animal tox studies will allow us to enter posiphen into a pivotal phase II/III two-year study in AD and/or PD patients to show efficacy. 1
