Intra-Cellular Therapies, Inc. (ITI)
presented preclinical data on ITI-007, its first in class dual 5HT2A
receptor antagonist/dopamine receptor phosphoprotein modulator (DPPM) at a
major medical meeting last week. The Company is developing ITI-007 for the
treatment of schizophrenia and other related psychiatric conditions.
In this presentation, ITI-007 was shown to possess a unique
pharmacologic profile, unlike any other existing antipsychotic drug. As a
dopamine protein phosphorylation modulator, ITI-007 normalizes brain
dopamine activity. At much lower doses and concentrations, ITI-007
selectively blocks 5HT2A receptors. Both of these actions are important for
antipsychotic drug action.
"We believe the large separation between activity at dopamine and
serotonin receptors will allow a personalized approach to patient treatment
for schizophrenia providing an ability to 'dial-in' the optimal D2 receptor
occupancy on an individual basis. This personalized approach will allow
physicians to tailor doses to achieve optimal antipsychotic efficacy
without inducing motoric or other side effects," stated Sharon Mates,
Ph.D., Chairman and Chief Executive Officer of Intra-Cellular Therapies.
In vivo, ITI-007 acted as a partial agonist at pre-synaptic dopamine
receptors. For example, ITI-007 provoked an intracellular phosphorylation
pattern consistent with the activity of a partial agonist at pre-synaptic
dopamine receptors, thereby preserving normal dopamine metabolism.
Furthermore, in the prefrontal cortex, a brain region profoundly affected
in patients with schizophrenia, ITI-007's effects on extracellular
concentrations of dopamine were consistent with a partial dopamine agonist
profile.
The Company's presentation demonstrated ITI-007 also has an affinity
for the serotonin reuptake site, an activity that potentially may be
beneficial in treating affective disorders.
ITI's CNSProfile(TM) has shown, unlike some atypical antipsychotics,
ITI- 007 does not exhibit significant potency for a variety of other
targets that have been implicated in a range of dose-limiting side effects
of antipsychotic drugs. ITI-007 does not interact with muscarinic or
histaminergic receptors and has a reduced affinity for adrenergic receptors
relative to other antipsychotic drugs and relative to its potency at 5HT2A
receptors.
About ITI-007
ITI-007 is an orally available compound that combines potent 5HT2A
receptor antagonism with cell-type-specific modulation of phosphoprotein
pathways downstream of dopamine receptors. As a dopamine receptor protein
phosphorylation modulator (DPPM), ITI-007 has dual properties; it acts as a
post-synaptic antagonist and as a pre-synaptic partial agonist. The
combination of ITI-007's high-potency blockade of 5HT2A receptors and
unique dopamine receptor activity will make it possible for the first time,
to select a clinical dose capable of saturating 5HT2A receptors while
permitting the 'dialing in' of an optimal amount of dopamine receptor
modulation by simple dose adjustments using a single drug. The ability to
optimize the level of dopamine receptor modulation holds promise for the
reduction of psychotic symptoms without incurring high levels of dopamine
antagonism that cause motor disturbances and other deleterious side
effects. In addition, the wide separation of affinity at 5HT2A and D2
receptors may allow for administration of the appropriate amount of
dopamine modulation for antipsychotic maintenance therapy and the treatment
of bipolar disorders.
ITI-007 has a much lower propensity than several currently marketed
antipsychotic drugs to interact with receptors that mediate deleterious
cardiovascular events, sedation, and rapid and significant weight gain.
About Schizophrenia
Schizophrenia is a major neuropsychiatric disorder that affects over 1%
of the world population with an illness that begins in late adolescence and
lasts a lifetime. Its best known symptoms are 'positive symptoms', which
include hallucinations and delusions; but other mental functions are also
affected, including social and motivational skills ('negative symptoms')
and cognitive behaviors, like inattention and poor memory. Current
antipsychotics are effective primarily on reducing positive symptoms but
leave negative and cognitive symptoms untouched. Not only are current drugs
incompletely active, but they also have limiting side effects, including
troublesome actions on motor function, weight gain, and metabolic symptoms
(diabetes and hyperlipidemia), along with sedation, constipation,
dizziness, and loss of bladder control. Few people with schizophrenia
regain normal psychosocial function; the medical need in this disease area
is enormous.
CNSProfile(TM)
The Company has developed a state-of-the-art technology platform,
called CNSProfile(TM) that is capable of generating a unique molecular
signature for drug compounds. Specifically, CNSProfile(TM) measures the
levels of phosphoproteins, proteins chemically linked at specific sites to
phosphates. This profile provides the Company with a proprietary and unique
window into the intracellular action of CNS drugs or drug candidates.
Intra-Cellular Therapies uses this platform in its drug discovery and
development efforts of proprietary compounds and also to evaluate
in-licensing opportunities.
About Intra Cellular Therapies
Intra-Cellular Therapies, Inc. (ITI), is a biopharmaceutical company
that is developing novel drugs for the treatment of diseases and disorders
of the Central Nervous System (CNS). Building on the science generated from
the Nobel Prize winning laboratory of Dr. Paul Greengard at The Rockefeller
University, the Company develops compounds that have the potential to treat
a wide range of diseases associated with the CNS, including schizophrenia,
sleep disorders, Parkinson's and Alzheimer's disease, cognitive deficits in
schizophrenia, depression, and female sexual dysfunction and other
disorders pertaining to Women's Health. To aid in the development process,
the Company incorporates its CNSProfile(TM), a state-of-the-art platform
that allows ITI to choose compounds with the strongest potential to succeed
in these difficult to treat diseases.
Intra-Cellular Therapies, Inc.
intracellulartherapies