Psychosis is a severe disorder of thought and can lead to severe distress and even death unless treated with antipsychotic drugs. Individuals with psychosis are unable to distinguish reality from fantasy. The individual is unable to differentiate among data originating from an external source and data arising from the inner self. This inability leads to delusions (misinterpretation of meaning) and hallucinations (misperceptions) and to a chain of social consequences which impair functioning.

Lifetime (chronic) psychosis is called schizophrenia and strikes early, in the teens and early twenties, and leads to terror, unfulfilled ambition, unemployment, poverty, homelessness, family disintegration, social isolation, and, too often, suicide.

Psychosis is one of the most costly and debilitating impairments in the world, directly affecting approximately 4% of all adults at some time in life. Psychosis is one of the most costly and debilitating impairments in the world, directly affecting approximately 4% of all adults at some time in life. Schizophrenia, the most costly form of psychosis, has a life-time prevalence of 1% of the entire human population in every country. 2.5% of US health care spending is on schizophrenia alone, a direct cost of over $40 Billion. There is a further  approxamiately $100 Billion in indirect costs.

Accordingly, it is one of the biggest of all drug markets: over $15 billion and growing. Three of the top 15 selling pharmaceutical drugs world-wide are antipsychotics for schizophrenia.  Current antipsychotic drugs have significant side effects including obesity, diabetes, sexual dysfunction, seizures and sudden death.

At the molecular level, there is the constant process of antipsychotic binding to D2, followed by antipsychotic dissociation and re-binding to D2.

"Typical" or traditional antipsychotics such as haloperidol and chlorpromazine disassociate very slowly from the D2 receptor, which contributes to Parkinsonism by reducing the access of dopamine molecules to the receptor.

"Atypical" antipsychotics, such as quetiapine, clozapine, remoxipride, paliperidone (9-hydroxy-risperidone), amoxapine, perlapine and aripiprazole, bind loosely and rapidly dissociate from D2 before re-binding. This "fast-off-D2 principle" provides microseconds of time to permit dopamine molecules access to D2 and this access, in turn, minimizes extrapyramidal (movement disorders) and related side-effects.

Current antipsychotic drugs, whether "typical" or "atypical", have significant side-effects including obesity, diabetes, dysphoria, sexual dysfunction, seizures and sudden death. There is a significant unmet medical need to identify and develop new medicines which are effective in treating psychosis and are free from the serious side-effects associated with current therapies.

Clera has developed a number of novel small-molecule drug candidates that have optimized "fast-off" affinity for D2 receptors and low affinity for other receptors, thereby reducing the risk of extrapyramidal signs, dizziness and cardiac effects. Based on receptor profiling, they are predicted to have strong antipsychotic activity and a low or no risk of Parkinsonism, hyperprolactinemia, tardive dyskinesia, obesity, diabetes or abnormal ECG.

If we are successful, patients will have fewer side-effects and better outcomes. As a result, they will keep taking their medicine, which they will most likely require for the rest of their lives.