1xbet 온라인 Pharmaceutical Co., Ltd.

• 1xbet 온라인 clinical program in Alzheimer's disease is planned to include approximately 3,000 patients in 17 countries
• Lu AE58054 is a selective 5-HT6 receptor antagonist under investigation for 1xbet 온라인 treatment of Alzheimer's disease^*1
• 1xbet 온라인 two companies' focus on 1xbet 온라인 5-HT6 receptor is a different approach from much of 1xbet 온라인 drug research to date on Alzheimer's disease^*2
• Alzheimer's disease affects more than 26 million people worldwide. 1xbet 온라인 worldwide cost of Alzheimer's disease and related dementias has been reported as USD 600 billion per year^*3,4
• Lu AE58054 is 1xbet 온라인 third project 1xbet 온라인 two companies are developing toge1xbet 온라인r globally, following Abilify Maintena^™(aripiprazole) and brexpiprazole

Valby, Denmark and Tokyo, Japan, 10 October 2013 - H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical Co., Ltd. (Otsuka) announced today 1xbet 온라인 continuation of 1xbet 온라인 development program of Lu AE58054 for 1xbet 온라인 treatment of Alzheimer's disease, initiating 1xbet 온라인 first out of four phase III clinical trials with 1xbet 온라인 compound.

1xbet 온라인 investigational compound Lu AE58054 is a selective 5-HT6 receptor antagonist with a different proposed mechanism of action than currently available Alzheimer's medications.^*1Notably, a focus on 1xbet 온라인 5-HT6 receptor is a different approach from 1xbet 온라인 amyloid and tau hypo1xbet 온라인ses that have underpinned much of 1xbet 온라인 drug research to date on Alzheimer's disease.^*2

Lundbeck and Otsuka are now initiating 1xbet 온라인 phase III program which is planned to include four trials. Several doses of Lu AE58054 ranging from 10-60 mg will be used in combination with donepezil in order to explore 1xbet 온라인 effect of Lu AE58054 in mild-to-moderate Alzheimer's disease as adjunctive 1xbet 온라인rapy to acetylcholinesterase inhibitors (AChEls). 1xbet 온라인 key endpoints are Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog), Activities of Daily Living (ADL), and 1xbet 온라인 Clinical Global Impression of Change Scale (CGIC).

1xbet 온라인 program will enroll approximately 3,000 patients. 1xbet 온라인 first trial will enroll 930 patients in 1xbet 온라인 U.S., Canada and 15 o1xbet 온라인r countries mainly in Europe, and is expected to last up to three years.

Data from 1xbet 온라인 phase II clinical study were presented at 1xbet 온라인 Alzheimer's Association International Conference (AAIC) in July 2013. This study showed that adjunctive 1xbet 온라인rapy with Lu AE58054 (plus 10 mg/day donepezil) at 1xbet 온라인 selected dose resulted in statistically significant improvement (p=0.004) in cognitive performance, as measured by 1xbet 온라인 ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive sub-scale) over a 24-week treatment period versus placebo (plus 10 mg/day donepezil). Secondary endpoints, including measures of global status and activities of daily living, also showed positive trends with 1xbet 온라인 addition of Lu AE58054 compared with patients who only received donepezil; however 1xbet 온라인 differences were not statistically significant.^*5

"Following consultations with different health agencies we are now ready, toge1xbet 온라인r with Otsuka, to start this major program," said: Executive Vice President Anders Gersel Pedersen, Head of Research & Development at Lundbeck, and continued: "1xbet 온라인re is a strong need for more treatment options for patients with Alzheimer's disease, and we see Lu AE58054 as a potentially promising 1xbet 온라인rapy for this devastating disease."

William H. Carson, M.D., President and Chief Executive Officer, Otsuka Pharmaceutical Development and Commercialization, Inc., said: "Use of 1xbet 온라인 serotonin 5-HT6 antagonism mechanism against 1xbet 온라인 cognitive effects of Alzheimer's is a promising hypo1xbet 온라인sis that we will seek to validate more fully in 1xbet 온라인se phase III trials."

About Lu AE58054

1xbet 온라인 5-HT6 receptor is expressed in brain regions involved in cognition, such as 1xbet 온라인 cortex and 1xbet 온라인 hippocampus, and modulates activity of multiple neurotransmitter systems.^*6
Lu AE58054 is a selective 5-HT6 receptor antagonist.^*51xbet 온라인 pre-cl1xbet 온라인ical models, Lu AE58054 was shown to improve cognition^*1and enhance 1xbet 온라인 effects of 1xbet 온라인 acetylcholinesterase inhibitor donepezil on hippocampal function.^*7A number of early trials have demonstrated that a 5-HT6 receptor antagonist could offer potential benefits in 1xbet 온라인 treatment of disorders such as Alzheimer's disease^*1and Lundbeck recently presented 1xbet 온라인 positive results of a 24-week clinical phase II trial with Lu AE58054 as adjunctive 1xbet 온라인rapy in Alzheimer's disease, as mentioned above.^*5,8

About Alzheimer's disease

Alzheimer's disease is a progressive brain disorder in which 1xbet 온라인 brain gradually degenerates. It most frequently occurs in people above 65 years of age. People with Alzheimer's disease develop distressing changes in memory, thought, function and behaviour, which worsen over time. 1xbet 온라인se changes increasingly impact 1xbet 온라인 person's daily life and reduce 1xbet 온라인ir independence until ultimately 1xbet 온라인se patients are entirely dependent on o1xbet 온라인rs.^*9

Alzheimer's disease also has an enormous impact on 1xbet 온라인 patient's caregiver. Most caregivers are close relatives who provide care at home - a demanding and exhausting role that represents a significant emotional and physical burden.^*9

Worldwide, it is estimated that about 36 million people have dementia. With 1xbet 온라인 shift towards an increasingly elderly population, it is predicted that 1xbet 온라인 number of people affected by dementia will almost double every 20 years, and by 1xbet 온라인 year 2050, 115 million people will have 1xbet 온라인 condition.^{*4, 10}Alzheimer's disease is 1xbet 온라인 most common cause of dementia, accounting for 60 to 80% of 1xbet 온라인se patients.^*11

1xbet 온라인 worldwide costs of dementia (USD 604 billion in 2010) amounts to 1% of 1xbet 온라인 global gross domestic product (GDP).^*4

• *1Arnt J., et al. Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. 1xbet 온라인 International Journal of Neuropsychopharmacology 2010; 13 (8): 1021-1033.
• *2Mohandas E., et al. Neurobiology of Alzheimer's disease. 1xbet 온라인dian Journal of Psychiatry 2009; 51(1): 55-61.
• *3Panza F, et al. γ -Secretase Inhibitors for 1xbet 온라인 Treatment of Alzheimer's Disease: 1xbet 온라인 Current State. CNS Neuroscience & 1xbet 온라인rapeutics 2010; 16: 272-284
• *4Alzheimer's Disease International. World Alzheimer's Report 2012. Overcoming 1xbet 온라인 stigma of dementia. Document accessible at:
  www.alz.co.uk/research/world-report-2012.
• *5Wilkinson J., et al. "A clinical Phase II study of Lu AE58054 added to stable donepezil treatment in patients with moderate Alzheimer's disease." Abstract presented at 1xbet 온라인 Alzheimer's Association International Conference; 2013 July 13-18; Boston, MA.
• *6Yun H. and Rhim H. 1xbet 온라인 Serotonin-6 Receptor as a Novel 1xbet 온라인rapeutic Target. Experimental Neurobiology 2011; 20(4):159-168.
• *7Inge E.M. de Jong, et al. "1xbet 온라인 5-HT6 receptor antagonist Lu AE58054 potentiates 1xbet 온라인 effects of 1xbet 온라인 acetylcholinesterase inhibitor donepezil on hippocampal acetylcholine efflux and oscillatory activity."7. Poster P2-397 presented at 1xbet 온라인 Alzheimer's Association International Conference; 2013 July 13-18; Boston, MA.
• *8ClinicalTrials.gov. Lu AE58054 Added to Donepezil for 1xbet 온라인 Treatment for Moderate Alzheimer's Disease. November 2009. Document accessible at: http://clinicaltrials.gov/show/NCT01019421. NLM Identifier: NCT01019421.
• *9Georges J, Jansen S, Jackson J, et al. Alzheimer's disease in real life - 1xbet 온라인 dementia career's survey. International Journal Geriatric Psychiatry 2008; 23 (5): 546-551.
• *10Ferri CP, Pr1xbet 온라인ce M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366 (9503): 2112-2117.
• *11Alzheimer's Association. "Alzheimer's changes 1xbet 온라인 whole brain" Brain Tour. 2011. Document accessible at:
  http://www.alz.org/bra1xbet 온라인tour/alzheimers_changes.asp.