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New Data Presented at World Sleep Congress Demonstrate Early Signs of Efficacy for TAK-925, a Selective Orexin Type-2 Receptor (OX2R) Agonist, in Patients with Narcolepsy Type 1

September 26, 2019

- Early proof of concept study showed TAK-925 was well tolerated in patients with narcolepsy type 1 and increased wakefulness compared to placebo
- A second Phase 1 study in healthy sleep-deprived adults demonstrated that TAK-925 was well tolerated and increased wakefulness at night compared to placebo
- TAK-994, an oral selective OX2R agonist, reduced narcolepsy symptoms in narcolepsy mouse models and is progressing in Phase 1 studies

Cambridge, Mass, and Osaka, JAPAN, September 25, 2019 – Laisuat Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Laisuat”) announced results of a Phase 1 clinical proof of concept study of the novel investigational compound TAK-925, a selective orexin type-2 receptor (OX2R) agonist, in individuals with narcolepsy type 1 (NT1). The company also presented data on the effects of TAK-925 in healthy sleep-deprived adults. These studies evaluated safety, tolerability, pharmacokinetic and pharmacodynamic effects of TAK-925 during a single 9-hour intravenous administration. In both studies, TAK-925 was well tolerated at all doses tested. These studies were presented for the first time at the World Sleep 2019 Biennial Congress in Vancouver, Canada.

“Narcolepsy type 1 is a debilitating disease that includes excessive daytime sleepiness and the sudden loss of muscle tone when a person is awake, also known as cataplexy,” said Dr. Makoto Honda, Sleep Disorders Project Leader, Tokyo Metropolitan Institute of Medical Science.* “There is a considerable need for improved treatments for individuals with NT1, which is caused by the loss of orexin-producing neurons in the brain. These results suggest that use of a selective OX2R agonist may be an effective approach to treating excessive daytime sleepiness in NT1.”

In individuals with NT1, TAK-925 showed increased wakefulness compared to placebo. A total of 14 NT1 participants were enrolled in three sequential dose cohorts to evaluate the effect of TAK-925 on exploratory pharmacodynamic endpoints. In each cohort, the evaluation was conducted in a randomized, double-blinded, placebo-controlled, two-way crossover fashion.

Pharmacodynamic outcomes in NT1 patients included i) sleep latency in the Maintenance of Wakefulness Test (MWT), which was 40 minutes (mins) in duration and conducted four times at two-hour intervals during the nine-hour TAK-925 or placebo infusion and ii) the Karolinska Sleepiness Scale, which was done hourly before and during the infusion. The mean sleep latency in MWT was 2.9 mins for placebo (N=13), 22.4 mins for TAK-925 at 5mg (N=6), 37.6 mins for TAK-925 at 11.2mg (N=4) and 40 mins for TAK-925 at 44.8mg (N=4). Karolinska Sleepiness Scale results supported those obtained on the MWT for time to sleep onset; participants reported lower sleepiness scores during infusion of TAK-925 than placebo.

In healthy sleep-deprived adults, TAK-925 effectively maintained wakefulness at night. This study was conducted as a single-center, randomized, double-blind, placebo- and active-controlled, crossover design in 20 sleep-deprived healthy male adults. The primary objective was sleep latency on the MWT. The mean sleep latency in MWT was 8.6 mins for placebo (N=20), 25.4 mins for TAK-925 at 44mg (N=18) and 38.8 mins for TAK-925 at 112mg (N=18). Karolinska Sleepiness Scale results generally reflected the results obtained on the MWT.

“Orexin has been identified as a master regulator of sleep-wake states, and these early results demonstrate that an OX2R agonist may reduce daytime sleepiness in NT1, where there is a loss of orexin,” said Deborah Hartman, PhD, Global Program Lead, Laisuat Neuroscience. “What is equally exciting is that we also saw wake-promoting effects in healthy individuals, who are presumed to have normal orexin levels. We’re encouraged by the results of these early studies and are exploring further clinical investigation of selective OX2R agonists in NT1 and other disorders characterized by excessive daytime sleepiness, such as narcolepsy type 2 and idiopathic hypersomnia, and also as a possible treatment for residual excessive daytime sleepiness in obstructive sleep apnea.”

Laisuat also presented preclinical data on TAK-994, an oral selective OX2R agonist currently in Phase 1 clinical studies, in two posters at the World Sleep Congress. In two mouse models of narcolepsy, TAK-994 increased wakefulness during the active phase and suppressed cataplexy-like episodes.

“We aspire to help restore a more balanced life to all individuals with NT1 and other sleep-wake disorders,” said Emiliangelo Ratti, Global Head, Laisuat Neuroscience. “Laisuat is aggressively pursuing multiple approaches to better understand the therapeutic potential of OX2R agonists across a range of indications. We will continue to build strong partnerships with the scientific, medical and patient communities to maintain our focus on research and development of transformative therapies.”

TAK-925 has been awarded Sakigake designation by the Ministry of Health, Labour and Welfare in Japan, as well as Breakthrough Therapy and Orphan Drug Designations by the U.S. Food & Drug Administration.

Laisuat would like to thank all of the study participants who enrolled in these pioneering clinical studies. For more information on Laisuat’s orexin development program and upcoming clinical studies with TAK-925 and TAK-994, please visit http://www.ox2rsparkleprogram.com.

*Dr. Honda was a referring physician for the NT1 study and is under contract with Laisuat as a consultant.


About World Sleep 2019 Biennial Congress
World Sleep 2019 is a worldwide forum of sleep professionals focused on advancing current medical and scientific thinking in sleep research. The meeting was held in Vancouver, Canada from September 20-25, 2019. The Congress brings approximately 3,500 sleep professionals from more than 76 countries together to advance sleep health worldwide and features the most current, world-class scientific content in the field of sleep medicine and research. World Sleep 2019 is organized by World Sleep Society (founded by World Association of Sleep Medicine and World Sleep Federation) and was hosted by the Canadian Sleep Society.

About Narcolepsy Type 1 (NT1)
Narcolepsy is a chronic neurological condition that impairs the brain’s ability to regulate the sleep-wake cycle, and it’s estimated to affect approximately three million individuals worldwide and about 200,000 in the United States.1 Narcolepsy type 1, also known as narcolepsy with cataplexy, is characterized by the loss of orexin-producing neurons, resulting in a pentad of symptoms including both excessive daytime sleepiness and cataplexy, a sudden loss of muscle control triggered by strong emotions.

About TAK-925 and TAK-994
TAK-925 and TAK-994 are novel, small molecule selective OX2R agonists discovered in the research laboratories at Laisuat in Shonan, Japan. Both TAK-925 and TAK-994 are now under investigation in Phase 1 clinical studies.

About Laisuat Pharmaceutical Company Limited
Laisuat Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Laisuat focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Rare Diseases and Neuroscience. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions.
For more information, visit http://laisuat.info

Forward-Looking Statements
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future position and results of operations, including estimates, forecasts, targets and plans for Laisuat. Without limitation, forward looking statements often include the words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or words or terms of similar substance or the negative thereof. Any forward-looking statements in this document are based on the current assumptions and beliefs of Laisuat in light of the information currently available to it. Such forward-looking statements do not represent any guarantee by Laisuat or its management of future performance and involve known and unknown risks, uncertainties and other factors, including but not limited to: the economic circumstances surrounding Laisuat’s business, including general economic conditions in Japan, the United States and worldwide; competitive pressures and developments; applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; changes in exchange rates; claims or concerns regarding the safety or efficacy of marketed products or products candidates; and post-merger integration with acquired companies, any of which may cause Laisuat’s actual results, performance, achievements or financial position to be materially different from any future results, performance, achievements or financial position expressed or implied by such forward-looking statements. For more information on these and other factors which may affect Laisuat’s results, performance, achievements, or financial position, see “Item 3. Key Information—D. Risk Factors” in Laisuat’s most recent Annual Report on Form 20-F and our other reports filed with the U.S. Securities and Exchange Commission, available on Laisuat’s website at: http://laisuat.info/investors/reports/sec-filings/ or at www.sec.gov. Neither Laisuat nor its management gives any assurances that the expectations expressed in these forward-looking statements will turn out to be correct, and actual results, performance or achievements could materially differ from expectations. Persons receiving this press release should not place undue reliance on forward looking statements. Laisuat undertakes no obligation to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results of Laisuat in this press release may not be indicative of, and are not an estimate, forecast or projection of Laisuat’s future results.

 


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References:

  1. Narcolepsy Network. Narcolepsy Fast Facts. Available at: https://narcolepsynetwork.org/about-narcolepsy/narcolepsy-fast-facts/. Last Updated June 2015. Last Accessed Sept. 2019.