Long-term toxicology studies for Posiphen; 6 month in rats and 9 months in dogs

标准杆18-820 摘要 Posiphen®的长期毒理学研究：大鼠6个月，狗9个月 酒石酸泊西芬是一种相对分子质量为487.5的小分子，其对数P为2.22. 可用性和高血脑屏障穿透性。它是神经毒性蛋白的翻译抑制物， APP、tau和α-突触核蛋白。通过抑制这些蛋白，Pophen使轴突运输正常化，降低 发炎和保护神经细胞免于死亡。这一新颖的机制承诺阻止或减缓 神经退行性变的过程，并为认知困难的人提供了生活在 健康独立的晚年生活方式。 为了在阿尔茨海默氏症和/或帕金森氏症患者中研究这种药物，我们需要在 动物。我们建议进行两项动物毒理学研究：一项为期6个月、为期1个月的老鼠研究 恢复和9个月的狗研究，1个月的恢复。在研究期间，这些动物将被 监测行为和安全性，研究结束后，将对器官和大脑进行评估 毒物学发现。 我们已经通过3项人体I期安全性研究取得了进展，ADCS开始了一项 2016年夏季轻中度AD患者的SILK IIa期药效学研究。 来自IIa阶段的数据与拟议的动物毒性研究的数据将使我们能够 将Posiphen纳入一项为期2至3年的AD患者II/III期关键研究，以显示其疗效。 阿尔茨海默病的领域一直被阻止对β或Remove进行处理的方法所主导 多种形式中的一种形式的β。泊西芬可阻止APP的合成，从而阻止Aβ的合成。相应地， 帕金森氏病使用类似的方法抑制α-突触核蛋白或LRRK的水平。再次振作起来 阻止α-突触核蛋白的合成。通过将APP/Aβ、tau/phopo-tau和α水平正常化- 突触核蛋白正酚可防止有毒物质的形成，并防止神经细胞死亡。 1

PAR 18-820 Summary 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 α-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 Aβ or remove Aβ in one of its many forms. Posiphen prevents the synthesis of APP and hence of Aβ. Accordingly the Parkinson’s field uses similar approaches to inhibit levels of α-synuclein or LRRK. Again posiphen prevents the synthesis of α-synuclein. By normalizing the levels APP/Aβ, tau/phopho-tau and α- synuclein posiphen prevents the formation of toxic products and prevents death of nerve cells. 1