Youth who are going to develop psychosis can be identified before their illness becomes full-blown 35 percent of the time if they meet widely accepted criteria for risk, but that figure rises to 65 to 80 percent if they have certain combinations of risk factors, the largest study of its kind has shown. Knowing what these combinations are can help scientists predict who is likely to develop the illnesses within two to three years with the same accuracy that other kinds of risk factors can predict major medical diseases, such as diabetes.

Plans for studies to confirm the results, a necessary step before the findings can be considered for use with patients in health-care settings, are underway.

The research was conducted in youth with a median age of 16 and was funded primarily by the National Institute of Mental Health (NIMH), part of the National Institutes of Health. Results were published in the January 7, 2008, issue of the Archives of General Psychiatry, by lead researchers Tyrone D. Cannon, Ph.D., of the University of California Los Angeles, and Robert Heinssen, Ph.D., of NIMH, with colleagues from seven other research facilities.

The combinations of factors that predicted psychosis included:

* deteriorating social functioning (for example, spending increasing amounts of time alone in one’s room, doing nothing);

* a family history of psychosis combined with recent decline in ability to function (such as a drop in grades not explained by other factors or an unexplained withdrawal from extracurricular school activities);

* increase in unusual thoughts (such as thinking that strangers’ conversations are about oneself);

* increase in suspicion/paranoia (such as suspicion of being followed); and

* past or current drug abuse.

“When teens have a dive in grades or drop out of the school band, and it happens against a backdrop of family history of schizophrenia and recent troubling changes in perception – like hearing nondistinct buzzing or crackling sounds, or seeing fleeting images that disappear with a second glance – more often than not it indicates that psychosis is fairly imminent,” Cannon said.

If participants had an unrealistic belief that they were being followed, for example, but could be shown that their troubling thoughts were unfounded, the researchers considered them as having a risk factor, but not yet psychosis. But if the participants’ sense of being followed became unshakable, despite evidence to the contrary, or became disabling, the researchers considered them as having crossed a threshold to psychosis.

Research shows that intervention during the early stages of psychosis improves outcomes, but it is not yet clear if even earlier intervention, before a psychotic illness develops, is effective.

“Having this more accurate ability to measure who’s likely to develop psychosis will be a great asset. Identifying young people in need of intervention is crucial, but the results of this research can help us do more than that. It can eventually help us determine the most effective time to intervene,” said NIMH Director Thomas R. Insel, M.D.

Researchers from the facilities that conducted the study used similar criteria and techniques to evaluate 291 high-risk youth, about three times as many as had been evaluated in any previous study of this kind. In addition to being smaller, earlier studies had used different criteria and measuring techniques from one another, which clouded the picture and resulted in only moderate accuracy in predicting psychotic illness.

In this study, a total of 35 percent of participants with at least one risk factor developed a psychotic illness within the 30-month study timeframe. However, when researchers broke the data down further, they found that the youth who had two or three additional risk factors developed psychosis at a rate of 68 to 80 percent, depending on which risk factors were combined.

A separate group of 134 healthy people with no known risk factors for psychosis served as a control group, for comparison. None of them developed a psychotic illness.

Researchers also found that the youth who progressed to a psychotic disorder tended to do so relatively quickly. Twenty-two percent developed psychosis within the first year of follow-up, an additional 11 percent by the end of the second year, and 3 percent more by two-and-a-half years (adding up to the total percentage of people – 35 percent – who developed psychosis in this study).

“The message here is that once we identify people as being high risk, we have a very good chance of knowing whether or not they’re likely to develop a serious mental disorder like schizophrenia and that, if they do, it will happen fairly quickly. That’s such a critical window of opportunity for getting them the help they need,” said Heinssen.

INVEGA™ (paliperidone) Extended-Release Tablets showed favorable long-term safety and tolerability during a one-year open-label extension (OLE) study, according to a new, company-sponsored study. In addition, patient symptom scores improved or were stable, on average, over this 52-week study1.

The study was designed to evaluate the long-term safety of INVEGA™, an oral, atypical anti-psychotic approved for the treatment of schizophrenia. Discontinuations due to treatment-emergent adverse events (TEAEs) and the total number of serious TEAEs were both six percent. Other assessments such as cardiovascular, metabolic and weight-related assessments showed either no mean change or clinically minimal change as a result of the treatment. Symptoms of schizophrenia were reduced during long-term open-label treatment in those patients that transitioned from placebo to INVEGA™ and were maintained in those that were previously on INVEGA™ as assessed by the Positive and Negative Symptoms of Schizophrenia (PANSSa) scores.

“This long-term extension trial adds to the body of knowledge regarding the safety of INVEGA™ in the longer-term treatment of schizophrenia. The study also suggests that symptom control is maintained over time,” said George M. Simpson, MD, Professor of Research, Director Outpatient Clinic, Keck School of Medicine of the University of Southern California. Dr. Simpson is a principal investigator of the study and a consultant to its sponsors Ortho-McNeil Janssen Scientific Affairs, LLC, Johnson & Johnson Pharmaceutical Research & Development, LLC, and Janssen, L.P., the company that markets INVEGA™.

The study consisted of 235 patients (154 male; 81 female) who had participated in the prior double-blind (DB) recurrence prevention study. This study demonstrated a significantly longer time to relapse in patients treated with INVEGA™ compared with those who received placebo and had been brought to an early completion when efficacy was established at its interim analysis. Of the 235 patients, 72 received INVEGA™, 80 received placebo, and 83 were enrolled directly into the OLE due to the early completion of the DB phase. These 83 patients had received INVEGA™ for a variable period of time prior to their entry into the OLE (sometime during the initial 14-week combined run-in and stabilization period).

Patients were 18-65 years old and met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria of schizophrenia for at least one year). The mean age of patients who entered was 35.8 years old.

Treatment in the OLE phase was initiated at a dose of 9 mg/day with changes in dose increments of 3 mg/day, to a maximum of 15 mg/day or minimum of 3 mg/day permitted.

Sixty percent of patients completed the OLE. TEAEs occurred in 69 percent of patients. The discontinuation rate due to adverse effects was six percent (n=12). TEAEs that occurred with an incidence of eight percent or more were tremor (13 percent; n=31), akathisia (11 percent; n=25), headache (eight percent; n=19), and insomnia (eight percent; n=18).

Safety for INVEGA™ was evaluated from OLE baseline to end point, in the context of a systematic review of TEAEs, clinical laboratory tests, body weight and body mass index, electrocardiograms and EPS incidence using the Simpson Angus Rating Scale, Barnes Akathisia Rating Scale and Abnormal Involuntary Movement Scale. Efficacy was evaluated as a secondary endpoint using the total PANSS score, with a negative score indicating a worsening of symptoms.

The mean changes observed in the total PANSS were:

-15.7±20.09 for patients who had been treated with placebo during DB, and who were then started on INVEGA™ during the OLE:

-6.3±18.91 for those initially assigned to INVEGA™ during DB, and then continued on INVEGA™ during the OLE; and

-3.9±13.85 for those 83 patients who had previously received up to 14 weeks of INVEGA™ while enrolled in the “run-in/stabilization phase” of the initial DB study (i.e. were never eligible for randomization to placebo), and who entered into the OLE directly.

Ortho-McNeil Janssen Scientific Affairs, LLC and Johnson & Johnson Pharmaceutical Research & Development, LLC sponsored this clinical study. Janssen, L.P, markets INVEGA™ in the U.S. Each of these companies is a subsidiary of Johnson & Johnson. Additional details about the study are available upon request.

For more information about Janssen, L.P., visit http://www.janssen.com.

Worldwide, it is estimated that one person in every 100 develops schizophrenia, one of the most serious types of mental illness. In the United States, there are currently two million people with schizophrenia, with men and women affected equally. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions, and social withdrawal), as well as by disorganized thinking.

INVEGA™, an atypical antipsychotic medication, was first approved in the U.S. in December 2006. It is approved for the acute and maintenance treatment of schizophrenia in the U.S. and for the treatment of schizophrenia in the E.U.

Important Safety Information For INVEGA™

INVEGA™ (paliperidone) extended-release tablets is indicated for the acute and maintenance treatment of schizophrenia.

Elderly Patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. INVEGA™ (paliperidone) is not approved for the treatment of patients with dementia-related psychosis.

The most common side effects that occurred with INVEGA™ were restlessness and extrapyramidal disorder (for example: involuntary movements, tremors and muscle stiffness). One risk of INVEGA™ is that it may change your heart rhythm. This effect is potentially serious, and you should talk to your doctor about any current or past heart problems. Some medications interact with INVEGA™. Please inform your health care professional of any medications or supplements that you are taking.

Neuroleptic Malignant Syndrome (NMS) is a rare and potentially fatal side effect reported with INVEGA™ and similar medicines. Call your doctor immediately if the person being treated develops symptoms such as high fever; stiff muscles; shaking; confusion; sweating; changes in pulse, heart rate, or blood pressure; or muscle pain and weakness. Treatment should be stopped if the person being treated has NMS.

Tardive Dyskinesia (TD) is a serious, sometimes permanent side effect reported with INVEGA™ and similar medications. TD includes uncontrollable movements of the face, tongue, and other parts of the body. The risk of developing TD and the chance that it will become permanent is thought to increase with the length of therapy and the overall dose taken by the patient. This condition can develop after a brief period of therapy at low doses, although this is much less common. There is no known treatment for TD, but it may go away partially or completely if therapy is stopped.

INVEGA™ should be used cautiously in people with a seizure disorder, who have had seizures in the past, or who have conditions that increase their risk for seizures.

INVEGA™ and similar medications can raise the blood levels of a hormone known as prolactin, causing a condition known as hyperprolactinemia. Blood levels of prolactin remain elevated with continued use. Some side effects seen with these medications include the absence of a menstrual period; breasts producing milk; the development of breasts by males; and the inability to achieve an erection. The connection between prolactin levels and side effects is unknown.

High blood sugar and diabetes have been reported with INVEGA™ and similar medications. If the person being treated has diabetes or risk factors such as being overweight or a family history of diabetes, blood sugar testing should be performed at the beginning and throughout treatment with INVEGA™. Complications of diabetes can be serious and even life threatening. If signs of high blood sugar or diabetes develop, such as being thirsty all the time, going to the bathroom a lot, or feeling weak or hungry, contact your doctor.

People with narrowing or blockage of the gastrointestinal tract (esophagus, stomach or small or large intestine) should talk to their health care professional before taking INVEGA™.

Some people taking INVEGA™ may feel faint or lightheaded when they stand up or sit up too quickly. By standing up or sitting up slowly and following your health care professional’s dosing instructions, this side effect may be reduced or it may go away over time.

Extrapyramidal Symptoms (EPS) are usually persistent movement disorders or muscle disturbances, such as restlessness, tremors, and muscle stiffness. If you observe any of these symptoms, talk to your health care professional.

Inform your health care professional if you are pregnant or if you are planning to get pregnant while taking INVEGA™. Do not breast-feed if you are taking INVEGA™.

INVEGA™ may affect your driving ability; therefore, do not drive or operate machines before talking to your health care professional. Avoid alcohol while on INVEGA™.

INVEGA™ may affect alertness and motor skills; use caution until the effect of INVEGA™ is known.

INVEGA™ may make you more sensitive to heat. You may have trouble cooling off, or be more likely to become dehydrated, so take care when exercising or when doing things that make you warm. INVEGA™ should be swallowed whole. Tablets should not be chewed, divided, or crushed. Do not be worried if you see something that looks like a tablet in your stool. This is what is left of the tablet after all the medicine has been released.

Janssen, L.P., based in Titusville, NJ, is the only pharmaceutical company in the U.S. dedicated solely to mental health. The company currently markets prescription medications for the treatment of schizophrenia, bipolar mania, and irritability associated with autistic disorder. For more information about Janssen, L.P., visit http://www.janssen.com.

1 Kramer M, Simpson G, Kushner S et al., Long-term safety/tolerability of paliperidone extended-release tablets: 52-week, open-label, extension phase of a schizophrenia symptom recurrence prevention study, December 2007

aPositive and Negative Symptoms of Schizophrenia (PANSS) is a standard rating scale used in trials to assess the severity of symptoms. The scale consists of 30 items, which are assessed from absent to extreme, and these are divided into both positive and negative symptoms

Johnson and Johnson
Johnson and Johnson

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.

http://www.intracellulartherapies.com

Titan Pharmaceuticals, Inc. (AMEX: TTP) announced that data from four Phase III efficacy and safety trials demonstrate that iloperidone, an investigational atypical antipsychotic, is associated with significantly greater improvements in the symptoms of schizophrenia versus placebo and has a favorable safety and tolerability profile.

These results were included as part of the recently filed New Drug Application (NDA) for iloperidone and were presented by Titan’s corporate partner, Vanda Pharmaceuticals, Inc., for the first time this week at a major psychiatric congress. The U.S. Food and Drug Administration (FDA) accepted the NDA submitted by Vanda for marketing approval on November 26, 2007.

The final Phase III study conducted by Vanda evaluated the efficacy of iloperidone versus placebo in patients with schizophrenia. The study was a randomized, double-blind, placebo-controlled, multi-center, four-week inpatient study that enrolled 604 patients. Following fixed-dose titration, inpatients were randomized to receive iloperidone at 24 mg/day, ziprasidone at 160 mg/day, or placebo. Patients treated with iloperidone had significantly greater improvements in Positive and Negative Syndrome Scale-Total (PANSS-T) scores than those on placebo and had PANSS-T improvement comparable to ziprasidone.

Iloperidone and ziprasidone showed similarly low effects on glucose, cholesterol, triglyceride and prolactin levels compared to placebo, and iloperidone was also associated with a favorable profile on the Extrapyramidal Symptoms Rating Scale (ESRS) versus placebo.

Additionally, iloperidone also had a similar akathisia profile to placebo, whereas ziprasidone was associated with a significant worsening of akathisia versus placebo on the Barnes Akathisia Scale (BAS), with 26 percent of patients experiencing a worsening of akathisia. Akathisia is a debilitating sensation of restlessness that can be unrelenting with symptoms that may occur around the clock.

A post-hoc, pooled analysis of three additional Phase III trials was also presented this week. Each trial was a randomized, double-blind, placebo- and active-controlled, parallel-group, six-week trial of patients with schizophrenia or schizoaffective disorder. The analysis evaluated change from baseline using the Brief Psychiatric Rating Scale (BPRS) for the 1,553 patients who remained on treatment for more than two weeks. Iloperidone demonstrated generally significant improvements over placebo in doses ranging from 4-8 mg/day to 20-24 mg/day; similar reductions in BPRS scores were observed at six weeks for iloperidone in doses of 20-24 mg/day, as compared to the active comparators risperidone and haloperidol. The analysis further demonstrated that iloperidone had a favorable safety profile, most notably with regard to extrapyramidal symptoms (EPS) and akathisia rates, weight and metabolic parameters, and prolactin levels.

Unmet Needs in Schizophrenia

Schizophrenia is a chronic, severe and disabling brain disorder that affects approximately one percent of Americans. Although there are many drugs approved to treat schizophrenia, including the commonly prescribed “atypical antipsychotics,” a high degree of dissatisfaction remains among physicians and patients. The recent CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study, conducted by the National Institute of Mental Health (NIMH) and reported in The New England Journal of Medicine, evaluated several antipsychotic medications and revealed that 74 percent of patients taking antipsychotics discontinued treatment within 18 months, primarily because of insufficient efficacy and tolerability issues.

About Titan Pharmaceuticals

Titan Pharmaceuticals, Inc. (AMEX: TTP) is a biopharmaceutical company focused on the development and commercialization of novel treatments for central nervous system disorders, cardiovascular disease, bone disease and other disorders. Titan’s products in development utilize novel technologies that have the potential to significantly improve the treatment of these diseases. Titan also establishes partnerships with government institutions and other leading pharmaceutical development companies.

http://www.titanpharm.com

The press release may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements include, but are not limited to, any statements relating to the Company’s development program and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company’s drug candidates, adverse side effects or inadequate therapeutic efficacy of the Company’s drug candidates that could slow or prevent product development or commercialization, the uncertainty of patent protection for the Company’s intellectual property or trade secrets, and the Company’s ability to obtain additional financing. Such statements are based on management’s current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release.

Titan Pharmaceuticals

The social behaviour of rats displaying schizophrenic tendencies is restored when they are treated with two new potential drugs that seem to have unique effects on dopaminergic signalling. This is a conclusion of a thesis from the Sahlgrenska Academy at Goteborg University in Sweden.

Schizophrenia is a severe psychiatric disorder with symptoms that include hallucinations and delusions. Other common effects are social withdrawal, lack of initiative, dulled emotions, and difficulty in experiencing pleasure.

“The treatment available for schizophrenic patients hardly ever relieves impairment of social function. If patients are to have satisfactory lives, we must find new drugs,” says pharmacologist Johan Rung, who has studied the two drug candidates, OSU6162 and ACR16.

In the studies, rats were given a type of drug known for inducing a schizophrenia-like state in humans, and this reduced the rats’ social behaviour. When the rats were given the two drug candidates, normal social behaviour was restored.

“This indicates that the two drugs can relieve the schizophrenic’s lack of ability to interact socially, and also have positive effects on a number of other symptoms thought to be caused by the same underlying mechanisms,” says Johan Rung.

In contrast to other drugs that only reduce dopaminergic signalling in the brain, the two new substances seem to be able to both reduce and strengthen the signalling, depending on the circumstances.

“This is a property that can be particularly beneficial in the treatment of schizophrenia. Different groups of symptoms can be linked to either elevated or reduced dopaminergic signalling in different parts of the brain,” says Johan Rung.

Titan Pharmaceuticals, Inc. (AMEX: TTP) announced that the U.S. Food and Drug Administration (FDA) officially accepted a New Drug Application (NDA) submitted for iloperidone, an investigational atypical antipsychotic for the treatment of schizophrenia. The NDA was submitted by Vanda Pharmaceuticals Inc. (NASDAQ: VNDA). The NDA includes data from 35 clinical trials and more than 3,000 patients treated with iloperidone. Acceptance of the NDA confirms that the application is sufficiently complete for FDA review.

Upon commercialization of iloperidone, Titan will receive a royalty of between 8-10% on worldwide sales.

In Phase III clinical testing, iloperidone has been demonstrated to be potentially safe and effective in the treatment of schizophrenia in both the acute and the chronic setting. In addition, iloperidone demonstrated a potentially favorable side effect profile, with low potential for weight gain and induction of diabetes, low extrapyramidal symptoms including akathisia, and low incidence of sleepiness and effects on cognition.

“We are very pleased with the acceptance of the iloperidone NDA for review by the FDA. This represents further progress towards potentially providing schizophrenia patients with a meaningful therapeutic option,” stated Dr. Marc Rubin, President and CEO of Titan Pharmaceuticals, Inc.

About Titan Pharmaceuticals

Titan Pharmaceuticals, Inc. (AMEX: TTP) is a biopharmaceutical company focused on the development and commercialization of novel treatments for central nervous system disorders, cardiovascular disease, bone disease and other disorders. Titan’s products in development utilize novel technologies that have the potential to significantly improve the treatment of these diseases. Titan also establishes partnerships with government institutions and other leading pharmaceutical development companies. For more information, please visit the Company’s website at http://www.titanpharm.com.

The press release may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements include, but are not limited to, any statements relating to the Company’s development program and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company’s drug candidates, adverse side effects or inadequate therapeutic efficacy of the Company’s drug candidates that could slow or prevent product development or commercialization, the uncertainty of patent protection for the Company’s intellectual property or trade secrets, and the Company’s ability to obtain additional financing. Such statements are based on management’s current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release.

Vanda Pharmaceuticals Inc. (Nasdaq: VNDA) announced that the U.S. Food and Drug Administration (FDA) has officially accepted the New Drug Application (NDA) for iloperidone, an investigational atypical antipsychotic for the treatment of schizophrenia. Acceptance of the NDA confirms that the application is sufficiently complete for FDA review.

About Schizophrenia

Schizophrenia is a chronic, severe and disabling brain disorder that affects approximately one percent of Americans. Patients suffering from schizophrenia exhibit a range of symptoms, which include positive symptoms such as hallucinations, delusions, negative symptoms such as emotional withdrawal and cognitive symptoms associated with significant impairment in social and occupational functioning.

Unmet Needs in Schizophrenia

Although there are many drugs approved to treat schizophrenia, including the commonly prescribed “atypical antipsychotics,” a high degree of dissatisfaction remains among physicians and patients. The recent CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study, conducted by the National Institute of Mental Health (NIMH) and reported in The New England Journal of Medicine, evaluated several antipsychotic medications and revealed that 74% of patients taking antipsychotics discontinued treatment within 18 months, primarily because of insufficient efficacy and tolerability issues.

About Vanda Pharmaceuticals Inc.

Vanda Pharmaceuticals Inc. is a biopharmaceutical company with a focus on the development and commercialization of clinical-stage product candidates for central nervous system disorders. The company has three product candidates in clinical development. In addition to iloperidone, Vanda is developing VEC- 162, a compound for the treatment of sleep and mood disorders which is currently in Phase III development for sleep disorders. Vanda’s third product candidate in clinical development, VSF-173, is currently in Phase II development for the treatment of excessive sleepiness. For more on Vanda Pharmaceuticals Inc., please visit http://www.vandapharma.com.

Note Regarding Forward-Looking Statements

This release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding Vanda’s plans for its product candidates. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “targets,” “likely,” “will,” “would,” “should,” and “could,” and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Vanda is at an early stage of development and may not ever have any products that generate significant revenue. Important factors that could cause actual results to differ materially from those reflected in Vanda’s forward-looking statements include, among others, a failure of Vanda’s product candidates to be demonstrably safe and effective, a failure to obtain regulatory approval for the company’s products or to comply with ongoing regulatory requirements, a lack of acceptance of Vanda’s product candidates in the marketplace, a failure of the company to become or remain profitable, Vanda’s inability to obtain the capital necessary to fund its research and development activities, a loss of any of the company’s key scientists or management personnel, and other factors that are described in the “Risk Factors” section (Part II, Item 1A) of Vanda’s report on Form 10-Q for the quarter ended September 30, 2007 (File No. 000-51863). No forward-looking statements can be guaranteed and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and Vanda undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

Researchers have identified a master regulatory molecule that is responsible for triggering the remodeling of neuronal connections critical for learning. Malfunctioning of the connection-remodeling machinery that they identified may also play a role in mental retardation, schizophrenia, and drug addiction. Thus, said the researchers, knowledge of the machinery could lead to insights into those disorders.

Peter Penzes and colleagues published their findings in the November 21, 2007, issue of the journal Neuron, published by Cell Press.

In their experiments, the researchers sought to understand the biological machinery controlling the enlargement of mushroom-like structures called dendritic spines on neurons. Such spines are the receiving stations for neurotransmitters — signaling chemicals that one neuron launches to trigger a nerve impulse in its neighbor. During learning, these spines strengthen signaling between neurons during the process of laying down memory pathways in the brain.

Spine structure can also be involved in neurological disorders. Researchers have found abnormal dendritic spines in certain types of mental retardation, including autism spectrum disorders, as well as schizophrenia and drug addiction.

Specifically, Penzes and colleagues sought to discover whether a molecule called kalirin-7 plays a role in spine enlargement in mature neurons when they undergo a learning-related strengthening called long-term potentiation (LTP).

The researchers theorized that kalirin-7 might be a key regulator of spine development because it is found in high concentration in the spines of mature neurons. Also, kalirin-7 was known to play a role in the remodeling of the structural beams and studs of the cell, called the cytoskeleton.

The researchers’ experiments with cultured neurons revealed that activation of neurons during LTP does indeed trigger kalirin-7 to turn on the machinery for remodeling spines, causing spines to become enlarged.

What’s more, the researchers found that kalirin-7 also regulates the other major process necessary for strengthening neuronal signaling connections. Kalirin-7 controls the number of neurotransmitter-receiving stations, called receptors, that festoon the surface of dendritic spines. The number of these receptors determines the strength of signaling connections between neurons.

The researchers concluded that their findings “strongly suggest that kalirin-7 may be an important regulator of the experience-dependent modifications of forebrain circuits during postnatal development and may play an important role in learning and memory.”

They also pointed out that altered spine structures “have been associated with mental retardation, neuropsychiatric disorders, and drug addiction. Specifically, aberrant spine morphology in forebrain occurs in many types of mental retardation, including fragile-X and autism spectrum disorders.” Similarly, they noted, studies of schizophrenics have also revealed such alteration of dendritic spines, as well as evidence of defects in the kalirin-7 pathway.

“Therefore, our results may suggest potential strategies for treatments of these neurodevelopmental and psychiatric diseases,” they wrote.

A new study, published in the November 2007 issue of Psychiatry 20071 found that the once daily formulation of SEROQUEL XL® in adult patients with schizophrenia significantly reduces the risk of psychotic relapse. The study was scheduled to last one year or until relapse, but significant differences in the relapse rate between active treatment and placebo required the study to be stopped early. Seroquel XL is currently not licensed in the UK and is known as Seroquel XR”! in the rest of the world.

Schizophrenia patients experience high rates of symptom relapse, and as a result, there is an important need for options for long-term treatment of schizophrenia.1,2,3

The randomised, double-blind study examined the time to first psychiatric relapse in 197 patients with clinically stable schizophrenia treated with either Seroquel XL (mean daily dose 669 mg/day) or placebo. As the study was terminated after a positive interim analysis the mean duration of the randomised phase was four months (120 days) and the maximum period was nine months (270 days).

In the interim analysis population, active treatment significantly increased the time to relapse (hazard ratio 0.16; p<0.0001) and significantly reduced the risk of relapse by 84% (p<0.0001) compared with placebo. Only 9 (10.7%) patients in the active treatment group experienced a relapse during the study compared with 36 (41.4%) patients in the placebo group, and 90% of Seroquel XL recipients remained relapse free for 2.9 months.

In addition to providing protection from relapse, Seroquel XL also significantly improved schizophrenia symptom scores on the Positive and Negative Syndrome Scale (PANSS) (47.15 vs. 48.86 for the placebo group at the last visit; p<0.01). Significant benefits were also seen in the Clinical Global Impression (CGI) scales for improvement and severity (p<0.001). No patients treated with Seroquel XL required hospitalisation due to worsening schizophrenia compared with 8.3% of placebo recipients.

References:

1. Peuskens J, Trivedi J, Malyarov S, Brecher M, Svensson O, Miller F, Persson I & Meulien D on behalf of the study D1444C00004 Investigators. Prevention of schizophrenia relapse with extended release quetiapine fumarate dosed once daily: a randomized, placebo-controlled trial in clinically stable patients. Psychiatry 2007. In press.

2. Kane JM. “Drug Therapy: Schizophrenia.” N Engl J Med. 1996; 334 (1): 34-41.

3. Robinson D et al. “Predictors of Relapse Following Response From a First Episode of Schizophrenia or Schizoaffective Disorder.” Arch Gen Psychiatry. 1999; 56: 241-247.

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The Seroquel SmPC is available on request or can be found at http://emc.medicines.org.uk

Note:

In the rest of the world Seroquel XL ® is known as Seroquel XL”!. In Seroquel XL is a trademark of the Astrazeneca group of companies.

About Seroquel

The U. S. Food and Drug Administration (FDA) approved Seroquel XL, known as XR in the US, in May 2007 for the treatment of schizophrenia in adult patients. The Netherlands regulatory authority Medicines Evaluation Board (MEB) has also approved Seroquel XL, and AstraZeneca has applied for a Mutual Recognition Procedure to seek similar approvals across Europe. AstraZeneca has filed for approval to the UK’s MHRA under a national licence.

Launched in 1997, Seroquel (quetiapine fumarate, immediate release) is licensed in 85 countries for the treatment of schizophrenia, in 73 countries for the treatment of mania associated with bipolar disorder, and in October 2006 it was approved in the US by the FDA for the treatment of bipolar depression.

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world’s leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.