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ABOUT CSP-1103

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CSP-1103 Overview

CSP-1103, an orally delivered tablet, has undergone Phase 2 testing in people with Mild Cognitive Impairment (MCI), and CereSpir is integrating the findings to finalize the Phase 3 clinical protocol in consultation with key opinion leaders in AD research and the U.S. Food and Drug Administration.   The Company aims to conduct a parallel program in Batten disease.

CSP-1103 is a novel, first-in-class, small molecule microglial modulator that protects neurons and other cells in the brain. The Phase 2 clinical program generated safety and efficacy data in approximately 100 people half of whom received CSP-1103 for up to 2 years.  Data from this study were presented at the Alzheimer’s Association International Conference in 2013 and 2014.  CereSpir is working to finalize the Phase 3 clinical protocols in consultation with key opinion leaders in AD research and the U.S. Food and Drug Administration.  The company aims to initiate the first Phase 3 trial in 2015.  CSP-1103 has been shown to inhibit brain amyloid beta (Aβ) plaque deposition, reduce tau pathology and neuro-inflammation and reverse associated memory deficits in AD transgenic mouse models. Additionally CSP-1103 restores normal microglial function by increasing phagocytosis and decreasing production of pro-inflammatory cytokines. Chronic dysfunction of microglia is increasingly believed to play an important role at the very beginnings of AD with several newly discovered genetic risk factors supporting this idea.  These effects of CSP-1103 may translate into preventing the memory loss that is the hallmark of AD. Microglia form an important part of the innate immune system of the brain and are small cells that migrate through the brain to remove waste products, such as the amyloid aggregates that cause inflammation and irreversible damage to nerve cells.  CSP-1103 binds strongly and selectively with the intracellular domain of the amyloid precursor protein (AICD) and inhibits its translocation to the nucleus to prevent transcription of pro-apoptotic genes and activation of GSK-3β, a multifunctional enzyme that is strongly associated with both tau pathology and inflammatory modulation.

The results from previous human clinical studies are consistent with a large body of preclinical data. Thus, for example, CSP-1103 rapidly and dose-dependently lowered cerebrospinal fluid (CSF) levels of two markers of neuro-inflammation, sCD40L and TNF-α, both in healthy volunteers and in MCI patients while prolonged treatment resulted in a reduction in CSF Tau (a marker of neurodegeneration) and was associated with sustained cognition.  Collectively, the preclinical and clinical studies suggest CSP-1103 acts as a microglial modulator capable of selectively reducing pro-inflammatory activities of microglial cells while increasing their ability to remove neurotoxic Aβ and Tau aggregates in the brain by phagocytosis.

CereSpir is planning to conduct a Phase 3 program for CSP-1103 using an enrichment strategy of biomarkers and other diagnostic criteria that would limit enrollment to patients with MCI due to AD.