Our lead product candidate is a novel small molecule that we have historically referred to as TC-1734 and now refer to as AZD3480.  In December 2005, we entered into a collaborative research and license agreement with AstraZeneca AB for the development and worldwide commercialization of AZD3480 (TC-1734) as a treatment for Alzheimer’s disease, cognitive dysfunction in schizophrenia and potentially other conditions marked by cognitive impairment such as attention deficit hyperactivity disorder (ADHD), age associated memory impairment (AAMI), and mild cognitive impairment (MCI).  

Phase 2 Clinical Trials in Alzheimer's disease and cognitive dysfunction in schizophrenia

AstraZeneca initiated a Phase 2b clinical trial of AZD3480 (TC-1734) in mild to moderate Alzheimer's disease in July 2007 and a separate Phase 2b trial for cognitive deficits in schizophrenia in August 2007. 

Phase 2 Clinical Trials in AAMI and MCI

In March 2006, we achieved statistically significant results in favor of AZD3480 (TC-1734) on all three co-primary endpoints in the 50mg AZD3480(TC-1734) dose group of a Phase 2 clinical trial in AAMI. The double blind, placebo controlled trial was designed to provide additional evidence as to whether AZD3480 (TC-1734) improves cognitive performance in cognitively impaired older adults. We recruited 193 subjects between the ages of 50 and 80, who were classified as having AAMI, to participate in the trial, of which 168 completed the trial. The trial design included three dose groups, 25mg AZD3480 (TC-1734), 50mg AZD3480 (TC-1734) and placebo, and dosing once daily for 16 weeks. The three co-primary endpoints were change from baseline on the power of attention and episodic memory factors included in a computer-based cognitive test battery developed by CDR Ltd. at the end of the 16-week dosing period and composite score on subject global impression, an overall cognitive performance self-rating scale, at the end of the 16-week dosing period, in each case as compared to placebo. In addition to the results in the 50mg dose group, we also achieved a statistically significant result in favor of AZD3480 (TC-1734) on the power of attention endpoint in the 25mg AZD3480 (TC-1734) dose group. AZD3480 (TC-1734) demonstrated a favorable safety profile in the trial and was generally well tolerated as compared to placebo. 

In 2004, we completed two Phase 2 clinical trials of AZD3480 (TC-1734), one in AAMI (n=71) and one in MCI (n=36), a condition marked by cognitive impairment that is more severe than AAMI but less severe than Alzheimer's disease. The primary objective of these trials was to assess the safety and tolerability of AZD3480 (TC-1734) in elderly persons. A secondary objective was to assess the ability of AZD3480 (TC-1734 to improve cognitive function as measured by the CDR test battery. In the trials, AZD3480 (TC-1734) was well tolerated at all doses tested below 150mg, and we observed positive effects on one or more aspects of cognition at doses that were well tolerated.   

In Vitro Neuroprotection 

While the exact causes of Alzheimer's disease and other cognitive impairments are unknown, the aging process is generally accompanied by a decline of cognitive function linked to a progressive deterioration and death of cells in the brain. If neurodegeneration reaches a more advanced stage, such as in Alzheimer's disease, a person becomes debilitated and unable to care for himself or herself. In two preclinical in vitro studies that we conducted, AZD3480 (TC-1734) protected neuronal cells from deterioration and death, a process known as neuroprotection.

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About Alzheimer's disease 

Alzheimer’s disease, the most common form of dementia, is a debilitating brain disorder for which there is no cure. The disease progresses in stages from mild to moderate to severe and gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate and carry out daily activities. Mild Alzheimer’s disease is characterized by mild forgetfulness and difficulty acquiring basic information and communicating. Moderate Alzheimer’s disease is characterized by forgetfulness, failure to recognize friends and family, disorientation regarding time and place and personality changes. Severe Alzheimer’s disease is characterized by difficulty performing simple tasks and activities associated with daily living. Patients with severe Alzheimer’s disease require continuous care.

The treatment of Alzheimer’s disease is currently dominated by a class of drugs called acetylcholinesterase inhibitors. Acetylcholinesterase inhibitors have limitations in that only about half of Alzheimer’s disease patients who take them show symptomatic improvement, and the drugs do not substantially delay the progressive deterioration and death of cells in the brain that can lead to more severe impairment and debilitation.

A 2007 report of the Alzheimer's Association estimates that there are more than 5 million Americans living with Alzheimer's disease, a 10% increase since 2002. The report also projects that, unless scientists discover a way to delay Alzheimer's disease, some 7.7 million Americans will have the disease by 2030.

About Cognitive Dysfunction in Schizophrenia

Schizophrenia is a chronic, severe and disabling form of psychosis. The disease is characterized by symptoms such as delusions, hallucinations, the inability to disregard familiar stimuli, sometimes referred to as sensory gating, disorganized speech, grossly disorganized or catatonic behavior and prolonged loss of emotion, feeling, volition or drive. In addition, schizophrenia is often marked by cognitive dysfunction, such as problems with attention, vigilance, memory, and reasoning that play a primary role in the inability of schizophrenic patients to function normally. Scientists have estimated that up to 75% of schizophrenic patients experience cognitive dysfunction.

Traditional treatments for schizophrenia are not effective to treat cognitive dysfunction in schizophrenia. While it has been reported that more recently developed treatments for schizophrenia, known as “atypical anti-psychotics,” may have some effect on cognitive dysfunction, the effect may not be lasting or lead to an improvement in daily activities. There are currently no drugs approved for the treatment of cognitive dysfunction in schizophrenia.

About AAMI

The term AAMI describes a common condition characterized by gradual memory loss or other cognitive impairment that generally occurs with normal aging. Otherwise healthy people at least 50 years old who score one standard deviation below the mean established for young adults on a standardized memory test may be classified with AAMI.  There are currently no drugs approved for the treatment of AAMI.

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