Tetra Discovery Partners, Inc. — Department of Health and Human Services SBIR Phase II: NIA

Description

Project Abstract Tetra Discovery Partners is seeking Phase II SBIR funding for a multiple ascending dose human Phase clinical trial of BPN to evaluate safety tolerability pharmacokinetic and cognitive profile in healthy young and elderly male and female subjects BPN is a first in class phosphodiesterase D negative allosteric modulator PDE D NAM that targets the protein kinase A cAMP response element binding protein PKA CREB pathway for synaptic plasticity The compound has the potential to show broad cognitive efficacy across a range of neurologic psychiatric and neurodevelopmental disorders Lead indications are the improvement of cognitive function in the elderly with age associated memory impairment and in patients with Alzheimer s disease Prior experience with BPN in a single ascending dose human Phase clinical trial indicates that the compound is absorbed after dosing by an oral route reaches a level in human blood projected to show cognitive efficacy based on animal studies and is well tolerated The clinical objectives of the multiple ascending dose study are the following To evaluate the safety and tolerability profile of multiple oral ascending dose levels of BPN in healthy young yr and elderly andgt yr subjects To characterize the steady state plasma PK profile of BPN following multiple oral administration in healthy young and elderly subjects To provide assessment of the cognitive effect of BPN in healthy young and elderly subjects The study will enroll up to subjects The number of subjects to be enrolled is a balance between the need to establish safety by exposing a limited number of subjects to the experimental drug versus enrolling an expanded number of subjects to explore potential efficacy The study will enroll sufficient subjects to obtain preliminary cognitive data to inform Phase b and Phase a studies but is not powered to detect small changes in cognition that might be clinically relevant in patients Steady state PK parameters will be compared between young subjects and the initial cohort of elderly subjects and an adjustment in dose will be made if needed As this is the first multiple dose study of BPN in humans safety assessment in young subjects is needed before evaluation of the drug in more vulnerable elderly subjects Cognitive assessments will include measures of verbal learning and memory visual learning pattern separation visual paired associate learning and measures of visual and verbal memory with hr delayed recall PDE D is a well validated target for improving cognition through modulation of the PKA CREB pathway for memory consolidation Compared to the assessment of immediate memory there have been few attempts to assess the effects of investigational drugs on longer forms of memory Should the Phase a study provide an indication of cognitive benefit in elderly subjects a larger Phase b trial will be designed to confirm and extend the results of the initial trial in elderly subjects with age associated memory impairment Project Narrative BPN is a novel first in class phosphodiesterase D negative allosteric modulator PDE D NAM being developed to treat cognitive impairment in Alzheimer s disease Currently over million Americans have been diagnosed with Alzheimer s disease while as the world s population ages there will be a quadrupling of patients world wide to million by There is a clear need for additional drugs to improve cognition in Alzheimer s patients beyond those currently available