— TPI 287 improves cognitive performance and reduces tau pathology —

— Activation of a critical neuronal cell signaling pathway and microglia activation by CRT 001 correlates with improved cognitive performance —

NEW YORK, Nov. 12, 2014 (GLOBE NEWSWIRE) -- Cortice Biosciences announced today results from studies supporting the efficacy of preclinical drug candidates, TPI 287 and CRT 001, for the treatment of neurodegenerative diseases associated with cognitive impairment. Results will be presented in a poster session on Friday, November 14 at the Cell Symposia for Translational Neuroscience in Arlington, VA and on Wednesday, November 19 at the Society for Neuroscience in Washington, D.C.

TPI 287 is a brain penetrable microtubule stabilizing agent, which may be effective in treating diseases associated with microtubule destabilization, known as tauopathies. TPI 287 is currently in Phase 1 clinical development for the treatment of the rare tauopathies, progressive supranuclear palsy and corticobasal dementia, as well as Alzheimer's disease. CRT 001 is a small molecule partial agonist of the beta1 adrenergic receptor, which was previously on the market for the treatment of heart failure, and which has been shown to have profound activity in models of Alzheimer's disease and Down syndrome.

Presentations are as follows:

Preliminary results from on-going studies confirm that TPI 287 effectively penetrates the mouse blood-brain barrier, which correlates with cognitive function improvements in the PS19 tauopathy animal model. These effects were demonstrated by improved performance in the Morris water maze, a highly regarded behavioral test for measuring pharmacologic effects on learning and spatial working memory. Cognitive improvements were associated with a reduction of phosphorylated tau protein, which is the primary constituent of the hallmark neurofibliary tangles in the brains of tauopathy patients. Together, these results validate use of brain penetrable microtubule stabilizing agents such as TPI 287 for the treatment of tauopathies. Clinical evidence supporting this approach could come following analysis of on-going clinical trials once complete. 

Noradrenergic signaling has been shown to play a critical role in learning and memory formation in animals, and to be significantly impaired in patients with Alzheimer's and other neurodegenerative diseases. Stimulation of the beta1 adrenergic receptor with CRT 001 has previously been shown to improve cognitive function. Preliminary results from on-going studies presented in these two poster presentations demonstrate the unique ability of CRT 001 to specifically activate biochemical signaling pathways associated with long-term memory gene activation. Unlike other effectors of noradrenergic signaling, CRT 001 stimulates only this particular signaling pathway and not other signaling pathways associated with cardiovascular and pulmonary responses triggered by other beta adrenergic receptor agonists.  The results also show that CRT 001 can improve a variety of cognitive functions in Alzheimer's disease mice whether administered acutely (1 hour prior to behavioral testing) or chronically (2-3 months prior to and during behavioral testing). In addition, CRT 001 was shown to have potential disease modifying affects by stimulating the activity of immune cells specific to the central nervous system, known as microglia, along with a concomitant reduction of the aberrant Alzheimer's plaque peptide, Abeta1-40. These results further support the potential of CRT 001 as a treatment for diseases associated with cognitive impairment. Cortice intends to advance this agent into clinical trials in 2015. 

"Results from these studies demonstrate the potential of our CNS drug development pipeline," said George Farmer, Ph.D., Chief Executive Officer of Cortice. "The striking impact of a microtubule stabilizing agent like TPI 287 on both cognition and tau pathology supports the potential outcome of on-going Phase 1 tauopathy trials evaluating this drug candidate. Furthermore, the unique properties of CRT 001, combined with the excellent safety and tolerability profile already demonstrated in thousands of clinical subjects, support our view of the excellent potential of this drug for treating high unmet medical needs associated with cognitive impairment."     

About TPI 287

TPI 287 is a taxoid that binds to and stabilizes the assembly of microtubules similarly to the taxanes, paclitaxel and docetaxel. Compared with these other taxanes, TPI 287 has the distinct advantage of being able to readily penetrate the blood-brain barrier. Microtubule stabilization by TPI 287 in the brain may have potential as treatment of neurodegenerative diseases known as tauopathies that are associated with dysfunctional tau protein and defective microtubule architecture. Accordingly, TPI 287 is being developed for the treatment of the tauopathies progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Alzheimer's disease (AD).  As an anti-cancer agent designed to inhibit cellular division and growth, TPI 287 is also being evaluated for the treatment of glioblastoma and secondary brain metastases.

About CRT 001

CRT 001 is a partial agonist of the beta1 adrenergic receptor, a family member of G-protein coupled receptors that control noradrenergic signaling, which are critical for learning and memory formation in mammals. Noradrenergic signaling is also significantly disrupted in diseases associated with dementia, including Alzheimer's disease.   CRT 001 was previously marketed in select European countries as xamoterol (Corwin) for the treatment of mild-to-moderate heart failure, and has been shown to be safe and well tolerated in over 70 published clinical trials that enrolled over 3,500 subjects. Based on this attractive clinical profile and highly compelling preclinical results, Cortice intends to develop CRT 001 for the treatment of diseases associated with cognitive impairment, which include Alzheimer's disease, Down syndrome, and several related orphan indications.    

About Cortice Biosciences

Cortice Biosciences, Inc. is a clinical-stage drug development company pioneering novel therapies for the treatment of oncologic and neurologic disease indications with urgent unmet medical need. More information can be found at www.corticebiosciences.com.

Safe Harbor Statement

This media release may contain forward-looking statements about Cortice Biosciences, which can be identified by the use of terminology such as "will," "would," "should," "expects," "anticipates," "intends," "plans," "believes," "may," "estimates," "predicts," "projects," or similar expressions intended to identify such statements.  These statements reflect the current views of Cortice with respect to future events, are based on assumptions, and subject to risks and uncertainties.