PT00114 is efficacious in animal models at low doses, has a rapid onset and a long duration of action. It acts, in part, by inhibiting the effects of corticotropin-releasing hormone (CRH), the main stress inducing hormone in the body. In animals, it crosses the blood-brain barrier and inhibits the effects of high stress and anxiety but has little effect in unstressed animals. Thus, PT00114 represents true stress-effect targeted therapy that is applicable to a wide range of mood disorders. This suggests that as a treatment, PT00114 has the potential to inhibit the harmful effects of stress on the patient without causing unwanted side effects.
The neuroprotective capability of PT00114 is the basis of its use in neurodegenerative disorders that are currently under investigation.
PT00114 is the first known example of a new class of brain-targeted therapies based on a newly-described and highly conserved family of neuropeptides that regulate stress-induced mood and addictive behaviors. PT00114 is believed to act via a novel mechanism of action and is therefore expected to provide an extremely attractive therapeutic and commercial profile, especially for those patients who are not fully responsive to or compliant with current interventions. Based on preclinical data, we believe that PT00114 is well differentiated from other drug candidates on the basis of having: dual activity on stress- and addiction-related pathways (as present in TRD and PTSD); blood-brain barrier permeability; rapid onset of action and long duration of therapeutic effects; restoration of normalcy in stress, anxiety and addiction disorders; no adverse effects with little to no accumulation; good safety and tolerability profiles; convenient dosing route and schedule; high potency/low dose; and, ease of chemical synthesis.
TCAP-1 is a promising treatment for anxiety and depression as it alleviates high stress response-related behaviours. Mechanistic studies found that it is because TCAP-1 ablates the effect of the stress-inducing hormone, CRF, thus resulting in the significant decline of anxious nature. Our current work aims to actively pursue therapies that harness the stress-diminishing capabilities of TCAP-1 in order to increase stress-response. By doing so, we can help reduce the manifestations of anxiety on a day-to-day basis.