ATI-9242 is designed to be a novel, next-generation atypical antipsychotic for the treatment of schizophrenia and other psychiatric disorders. We believe this product will improve upon the efficacy of the best atypicals while avoiding metabolic drug-drug interactions and minimizing certain other metabolic problems associated with atypicals, including weight gain and type 2 diabetes. The receptor profile of ATI-9242 is designed to treat negative symptoms of schizophrenia - reduction in social interaction, disassociation from people or settings, monotone speech, loss of feelings of pleasure - and enhance cognitive functions. We entered the clinic with ATI-9242 in April 2008.

Schizophrenia

Schizophrenia is a chronic disorder afflicting up to 1% of the world’s population. Global sales of antipsychotics were greater than $15 Billion in 2006, and the cost of care has been estimated to account for 2.5% of annual U.S. health care expenditures.

Limitations of Currently Marketed Antipsychotics

Common side effects shared by first-generation antipsychotic drugs, the so-called typical antipsychotics, include certain types of involuntary muscle contractions or movement, cardiovascular effects, and sedation. Long-term use of these agents can result in over production of prolactin in males and females, affecting menstrual cycles or sexual function, and movement disorders such as tardive dyskinesia, or involuntary, repetitive, and purposeless movements. Second-generation antipsychotics, the so-called atypical antipsychotics, such as clozapine and olanzapine, quetiapine, and others, are associated with serious and potentially fatal adverse effects. Clozapine, the first atypical antipsychotic, is still considered the most efficacious but is associated with agranulocytosis, or a serious reduction in white blood cells, in 0.5%-1% of patients, and seizures in about 2% of patients. In addition, clozapine and other atypicals can be associated with weight gain, type 2 diabetes, sedation, and orthostatic hypotension which results in a significant lowering of blood pressure when moving from sitting or lying to a standing position. None of the currently available atypicals addresses the negative symptoms – reduction in social interaction, disassociation from people or settings, monotone speech, loss of feelings of pleasure – and the cognitive deficit associated with schizophrenia.

ATI-9242 Preclinical Studies

In vitro receptor profiling has demonstrated that ATI-9242 has moderate D2 receptor affinity and a high 5HT2A/D2 binding ratio characteristic of atypical antipsychotic agents. In addition, ATI-9242 binds with high affinity to the 5HT7 receptor and exhibits 5HT1A partial agonist activity. In rat cortical neurons, ATI-9242 potentiates NMDA current and facilitates GABAergic neurotransmission. In rats, it increases dopamine and acetylcholine in the prefrontal cortex, with no measurable increase in the nucleus accumbens. ATI-9242 has no antimuscarinic properties.

ATI-9242 Development Status

We initiated a Phase 1 study with ATI-9242 in April 2008.

More Information

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