Our lead program is ready to start a clinical Phase II study on agitation and psychosis in Alzheimer's disease dementia patients
Exciva's lead project is built upon two innovative drug development approaches targeting the symptomatic management of Alzheimer’s disease dementia that have recently emerged after decades of preclinical and clinical research .
Exciva combines dextromethorphan with EXV-801, a triple-acting agent that is a CYP2D6 inhibitor and a 5-HT2A/2C receptor inverse agonist.
When combined, these two novel modes of action (dextromethorphan and 5-HT2A/2C receptor inverse agonism) will deliver a broad and synergistic treatment targeting various domains of neuropsychiatric symptoms associated with dementia, including hallucinations, delusions, aggression, agitation, depression, apathy, insomnia, aberrant motor behavior, etc.
Neuropsychiatric symptoms of dementia
Neuropsychiatric symptoms of dementia (NPS) are the leading cause of institutionalization of patients with Alzheimer’s disease and other dementias and constitute the major source of caregiver distress.
The term NPS covers a range of symptoms including agitation/aggression, anxiety, depression, apathy, irritability, disinhibition, delusions/hallucinations, etc. These symptoms are distinct in clinical presentation and are often considered mutually exclusive. Indeed, patients rarely display all of the symptoms simultaneously. Conversely, clinical experience indicates that there is rarely a patient with just one specific symptom. For instance, a frequently observed cluster of symptoms in AD could be aggression, agitation, wandering, repetitiveness, anxiety, while a common constellation of symptoms in a patient with vascular dementia cluster could incorporate confusion and restlessness.
Neurodegenerative diseases like AD are characterized by progressive neuronal cell death resulting in overall brain atrophy. This does not only result in accentuated neuronal loss in certain brain areas initially, but also leads to the pathology spreading to other brain regions as the diseases progress. As different brain areas are responsible for different functional roles, this explains why more advanced stages of the disease, with more widespread and generalized brain atrophy, are accompanied by a wider spectrum of symptoms.
Besides NPS in Alzheimer’s disease and other dementias, we also envisage that Deraphan could be effective in the treatment of similar symptoms in other diseases, expanding our pipeline of therapeutic area targets.