Aculys Pharma Initiates a Phase 3 Trial of pitolisant Treating Patients with Excessive Daytime Sleepiness Associated with Obstructive Sleep Apnea Syndrome

Minato-ku, Tokyo, Japan, January 24 2023 — Aculys Pharma, Inc. (“Aculys”), a clinical stage biopharmaceutical company focused on commercializing innovative treatments for neurological conditions, announced the initiation of a phase 3 clinical study of pitolisant (), a histamine H3 receptor antagonist/inverse agonist in patients with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea syndrome (OSAS), in Japan

This trial is a multi-center, randomized, double-blind, placebo-controlled, parallel-group study (Part 1) and a subsequent multi-center, open-label, long-term extension study (Part 2) to assess the safety and efficacy of pitolisant in the Japanese patient population. ―― Additional study details can be found here: https://jrct.niph.go.jp/latest-detail/jRCT2031220501

Aculys has an exclusive license to develop and commercialize pitolisant in Japan. Pitolisant, developed by Paris-based Bioprojet, was approved by the European Medicines Agency (EMA) for the treatment of “excessive daytime sleepiness associated with obstructive sleep apnea syndrome (OSAS)” in 2021, and has since been available in the clinical setting.

OSAS is characterized by an interruption of proper breathing due to the narrowing or obstruction of the upper airway during sleep. Typical symptoms include loud snoring, daytime sleepiness, insomnia, sense of insufficient deep sleep, and systemic fatigue. If OSAS is not properly treated, in the medium- to long-term, patients may develop complications such as diabetes, depression, hypertension, arteriosclerosis, and other cardiovascular conditions1,2.

Continuous Positive Airway Pressure (CPAP) is considered the standard treatment in OSAS and is used to mitigate the narrowing and obstruction of the upper airway and is known to contribute to improving various OSAS symptoms and patients’ quality of life (QOL). However, some patients reportedly experience persistent excessive daytime sleepiness despite appropriate basic treatment, and excessive daytime sleepiness is considered a risk factor for impact on labor productivity, reduced quality of life, and accidents such as traffic accidents, so new treatment options are needed.

Aculys Pharma is committed to bringing this drug to patients with OSAS in Japan as early as possible and aims to help achieve a society where people with OSAS and their family members live their lives to the fullest potential.

About Pitolisant
Pitolisant is an antagonist/inverse agonist that selectively binds to the histamine H3 receptor, an autoreceptor located in the presynaptic region of the histamine-containing neurons in the human brain that plays a critical role in regulating sleep and wake rhythm. The drug was created by Paris-based Bioprojet and was approved by the European Medicines Agency (EMA) for the treatment of “narcolepsy with or without cataplexy” in 2016 and for the treatment of “excessive daytime sleepiness associated with obstructive sleep apnea syndrome (OSAS)” in 2021. In the United States, the drug was approved by the Food and Drug Administration (FDA) for the treatment of “excessive daytime sleepiness associated with narcolepsy” in 2019 and “cataplexy associated with narcolepsy” in 2020.

About Aculys Pharma, Inc.
Aculys Pharma is a clinical stage biopharmaceutical company focused on the commercialization of neurology innovations for patients in Japan. Aculys was formed in 2021 as a catalyst to neurology innovation access. We are committed to shortening the drug lag in Japan by developing and commercializing novel CNS treatments; applying blockchain and AI technologies to increase speed to market; and providing services to improve medical care for patients, their families, healthcare professionals, and society.

Company name: Aculys Pharma, Inc.
Address: 2-14-4 KitaAoyama, Minato-ku,Tokyo, Japan
Representative: Kazunari Tsunaba
Established: January 2021
URL: https://aculys.com

Information concerning pharmaceutical products (compound under development) contained herein is not intended as advertising or as medical advice but intended for disclosure of management information.

[Media contact]
Aculys Pharma Communications Office (within Cosmo Publication Relations Corporation)
aculys_pr@cosmopr.co.jp

Mika Shirai, Aculys Pharma 
mshirai@aculys.com

References:
1. The Japanese Circulation Society. JCS Joint Working Groups for Guidelines for Diagnosis and Treatment of Cardiovascular Diseases (2008-2009 joint research team report) Guidelines for Diagnosis and Treatment of Sleep Disordered Breathing in Cardiovascular Disease
2. Clinical Practice Guidelines for Sleep Apnea Syndrome (SAS) 2020 (edited by committee preparing Clinical Practice Guidelines for Sleep Apnea Syndrome (SAS)
3. Update on Persistent Excessive Daytime Sleepiness in OSA; Chest . 2020 Aug;158(2):776-786.
4. The economic and societal burden of excessive daytime sleepiness in patients with obstructive sleep apnea. Sleep Med Rev. 2020 Jun;51:101275.

Aculys Pharma and Four H Initiate Research Collaboration using Wearable Devices to Study Sleep Disorders in Japan

  • Using digital biomarkers to assess patients’ sleep and daytime activity
  • Research could result in a more multifaceted and higher-quality approach to evaluating treatment efficacy
  • Sleep disorders represent an unmet medical need in Japan, including serious co-morbidities, quality of life, and social issues
Tokyo, Japan, January 24, 2023 — Aculys Pharma, Inc. (“Aculys”), a company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, and Four H, Inc. (“Four H”), a Japan- based company specializing in health technology, announced an exploratory research collaboration using wearable devices to help patients with narcolepsy and excessive daytime sleepiness (EDS) associated with obstructive sleep apnea syndrome (OSAS). In its quest to establish a new pharmaceutical model, Aculys is promoting DX (digital transformation) in clinical trials and medicine. In this collaborative exploratory study to be launched in collaboration with Four H, Aculys will collect trial participants’ subjective assessments of their sleep as well as data on their sleep, activities, and heart rate acquired from wearable devices to be worn each night during the clinical trial period. These data will be analyzed in conjunction with other data to be obtained in the clinical trial with the goal of identifying sleep-related digital biomarkers.

This exploratory research program will be characterized by the following three points:

  1. Objective understanding of narcolepsy, OSAS, and its characteristics (sleep condition, daytime sleepiness, etc.)
  2. Analysis using AI and other methods to collate the subjective assessment by patients and objective assessment obtained by the wearable device
  3. Development of appropriate and reliable digital biomarkers for future clinical trials and clinical setting

Through the above new approach, which is unprecedented in conventional clinical trials for sleep-related diseases, the following outcomes are expected: objective understanding of patients’ sleep status, analysis of daytime sleepiness patterns, extraction of sleep characteristics, and daytime activity data through comparison with people without symptoms, and detection of predictive signs of the onset of daytime sleepiness.

Sleep disorders are difficult to objectively identify, and largely rely on the memory and self-reporting of patients themselves, causing a range of challenges in diagnoses and appropriate treatment.

This exploratory research will allow a further accurate understanding of each patient’s sleep and lifestyle patterns, which had been difficult to measure previously. Over the long term, we collectively plan to build a comprehensive sleep ecosystem for patients, including: digital biomarkers which can be used to predict health risks; personalized data to improve patient quality of life and productivity; and quality disease management programs that patients can utilize at home.

About Sleep Disorders* in Japan
The impact of sleep-related disorders on Japanese society is enormous. Research shows that presenteeism (decreased productivity at work due to health issues) and absenteeism (absence or sick leave due to health issues) is causing an economic loss of about 3% of Japanese GDP, equivalent to about 15 trillion yen1. Japanese people also sleep less than people in other countries due to lack of understanding about the importance of sleep. The Japanese government’s “National Health Promotion Movement in the Twenty-First Century (Health Japan 21)” includes sleep as one of the key themes in attempting to raise awareness2-3.

Sleep disorders are also factors that interfere with proper sleep and daytime sleepiness. It has been reported that delays in appropriate medical intervention for sleep disorders and complications associated with sleep disorders (e.g., cardiovascular diseases, depression) increase overall costs to society including medical care expenditure4-7. In order to improve the patient’s quality of life, prognosis, productivity, and other factors, it is necessary to detect sleep disorders accurately and provide appropriate medical care at an early stage.

*General term for sleep-related illnesses, including insomnia, sleep-related breathing disorders (e.g., OSAS), and central hypersomnia (e.g., narcolepsy)

About Four H, Inc.

Health infrastructure is a must-have in order to maintain the healthy lives of people so that they can fulfill active lives in pursuit of happiness. Our mission is to foster the health industry that supports good health. By building an infrastructure for people to stay healthy, and by working together with medical institutions, pharmaceutical companies, medical device manufacturers, and health-related companies, we aim to create a society where people can strive to maintain good health, even before they become ill.

Company name: Four H, Inc.
Address: LINK SQUARE SHINJUKU 16th floor, 5-27-5 Sendagaya Shibuya-ku Tokyo, Japan
Representative Director: Atsushi Koshio
Established: June 2020
URL: https://www.four-h.co.jp

About Aculys Pharma, Inc.

Aculys Pharma is a clinical stage biopharmaceutical company focused on the commercialization of neurology innovations for patients in Japan. Aculys was formed in 2021 as a catalyst to neurology innovation access. We are committed to shortening the drug lag in Japan by developing and commercializing novel CNS treatments; applying blockchain and AI technologies to increase speed to market; and providing services to improve medical care for patients, their families, healthcare professionals, and society.

Company name: Aculys Pharma, Inc.
Address: The ARGYLE Aoyama, 2-14-4 Kitaaoyama, Minato-ku, Tokyo, Japan
Representative: Kazunari Tsunaba
Established: January 2021
URL: https://aculys.com

References:

  1. Hafner M et al. Why Sleep Matters-The Economic Costs of Insufficient Sleep. Cambridge, UK: RAND Europe; 2016
  2. OECD (2009), Society at a Glance 2009: OECD Social Indicators, OECD Publishing, Paris.
  3. Ministry of Health, Labour and Welfare, 2019 research report on health and nutrition of Japanese nationals
  4. Lyons MM, et al. Global burden of sleep-disordered breathing and its implications. Respirology 2020 Jul;25(7):690-702.
  5. Skaer TL, Sclar DA. Economic implications of sleep disorders. Pharmacoeconomics 2010;28(11):1015–23.
  6. Leger D, Bayon V, Laaban JP, et al. Impact of sleep apnea on economics. Sleep Med Rev 2012;16: 455–62.
  7. Flores NM, Villa KF, Black J, Chervin RD, Witt EA. The humanistic and economic burden of narcolepsy. J Clin Sleep

The information on pharmaceuticals contained in this release is for the purpose of disclosing our management information, and is not intended as a promotion or advertisement for the pharmaceuticals concerned.

Contact

Aculys Pharma Communications Office (c/o Cosmo Public Relations Corporation)
aculys_pr@cosmopr.co.jp

Mika Shirai, Aculys Pharma
mshirai@aculys.com

Public Affairs Department, Four H
info@four-h.co.jp

Aculys Pharma initiates a phase 3 clinical study of a diazepam nasal spray: an antiepileptic drug for the treatment of epileptic seizures

Aculys Pharma, Inc. (“Aculys Pharma” Headquarters: Minato-ku, Tokyo; Representative Director and CEO: Kazunari Tsunaba), a company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, announced that it has initiated a phase 3 clinical study of a diazepam nasal spray (compound development code: NRL-1), an antiepileptic drug for the treatment of status epilepticus or epileptic seizures that may lead to status epilepticus. 

This phase 3 study, conducted in Japan, is a multi-center, open-label study in children with status epilepticus and those at risk for status epilepticus to assess the efficacy and safety of NRL-1. Please visit the following site for detailed information on the study.

https://jrct.niph.go.jp/en-latest-detail/jRCT2031220265

NRL-1 was developed by the U.S. pharmaceutical company Neurelis, Inc. Aculys Pharma has obtained an exclusive license to develop and commercialize it in Japan and the Asia-Pacific region (excluding Greater China and Singapore) and is currently developing it in Japan. In 2020, Neurelis obtained approval from the U.S. Food and Drug Administration for its diazepam nasal spray (trade name in the U.S.: VALTOCO®) as an acute treatment for intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters or acute repetitive seizures) that are distinct from an individuals’ usual seizure pattern in adult and pediatric patients 6 years of age and older.

The cause, symptoms, and severity of epileptic seizures vary widely among people with epilepsy, and epileptic seizures themselves exhibit diverse characteristics in each person. Among the diverse seizure types, some people experience seizures that recur many times a day or that do not terminate after a certain period of time (status epilepticus). These patients are at increased risk of brain damage and reduced life expectancy.1 When repetitive seizures occur, people with epilepsy must seek emergency treatment by healthcare professionals. On average, it takes 40 minutes from the time an emergency call is placed until a person is transferred to a hospital for treatment.1An extensive, online, U.S.  survey of patients, their families, and physicians has reported that recurrent epileptic seizures cause significant emotional, social, and financial burdens on patients and their families.2

To improve quality of life for people with recurrent epileptic seizures and their families/care partners, Aculys Pharma aims to bring this product to Japan as soon as possible. 

Aculys Pharma also is collaborating with external partners to conduct surveys in Japan to identify challenges for people with epilepsy. The data will help guide development of a medical care plan for people with acute seizures, enabling more rapid responses to these episodes. As part of its mission, Aculys will continue to contribute to Japanese society by identifying healthcare issues from a social point of view and finding solutions through new technologies and developing external partnerships.

(*In the Asia Pacific region, Aculys has exclusive rights to Australia, Brunei, Cambodia, Indonesia, South Korea, Laos, Malaysia, Myanmar, New Zealand, the Philippines, Thailand, and Vietnam)

■About Diazepam nasal spray

Diazepam has been used in Japan for more than 60 years as a therapeutic agent, for the treatment of epileptic seizures, in various forms, including injections.  It also has a history of use as a suppository by non-medical personnel, such as patients and caregivers, outside of medical institutions.

■About epilepsy

Epilepsy is a chronic brain disorder that causes loss of consciousness and/or convulsions (epileptic seizures) as the result of excessive electrical excitation of nerve cells (neurons) in the brain. An estimated 600,000 to 1,000,000, or 5 to 8 in 1,000 people in Japan have epilepsy. As treatment has advanced, many people with epilepsy are able to control their seizures with appropriate diagnoses and antiepileptic medications; however, about 30% of people continue to experience frequent, repeated seizures f that require immediate treatment.3,4

■About Neurelis

Neurelis, Inc. is a commercial-stage neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and orphan neurologic disorders characterized by high unmet medical need. In 2020, the FDA approved Neurelis’ VALTOCO® (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from an individual’s usual seizure pattern in adult and pediatric patients six years of age and older. VALTOCO is a proprietary formulation of diazepam incorporating the science of INTRAVAIL®. INTRAVAIL’s transmucosal absorption enhancement technology enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. In its approval of VALTOCO, the U.S. Food and Drug Administration also granted Neurelis Orphan Drug Exclusivity and recognized VALTOCO’s intranasal route of administration as a clinically superior contribution to patient care over the previously approved standard-of-care treatment (a rectal gel formulation of diazepam). For more information on VALTOCO, please visit www.valtoco.com.  

Source:

1 The Japanese Society of Child Neurology. The guidelines for the treatment of status epilepticus in children 2017. [In Japanese]

2  Penovich PE, Buelow J, Steinberg, et al. Burden of seizure clusters on patients with epilepsy and caregivers survey of patient, caregiver, and clinician perspectives. The Neurologist. 2017;22:207–214.

3 Epidemiological survey on the prevalence, diagnosis, and treatment of epilepsy and issues to be solved to establish a healthcare system for the disease, MHLW grant survey 201317043B, 2013.   [Japanese Only]

4  Kwan P, MJ Brodie. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314–9.

■ About Aculys Pharma, Inc.

Aculys Pharma is a biopharmaceutical company focused on the development and commercialization of innovations in the fields of neurology and psychiatry. Its corporate name was created from the philosophy of serving as a “Catalyst to Access.”  Aiming to act as a bridge for innovative medical care in the field of neuropsychiatry, Aculys Pharma develops and commercializes novel pharmaceuticals and provides innovations for better medical care to patients, their families, healthcare professionals, and society.

Company name: Aculys Pharma, Inc.

Address: 2-14-4 KitaAoyama, Minato-ku,Tokyo, Japan

Representative: Kazunari Tsunaba

Established: Jan 2021

URL: https://aculys.com

 

Information concerning pharmaceutical product (compound under development) contained herein is not intended as advertising or as medical advice, but intended for disclosure of management information.

Aculys Pharma initiates a phase 3 clinical study of the histamine H3 receptor antagonist/inverse agonist pitolisant in patients with narcolepsy in Japan

Aculys Pharma, Inc. (“Aculys Pharma” Headquarters: Minato-ku, Tokyo; Representative Director and CEO: Kazunari Tsunaba), a company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, announced that it has initiated  a phase 3 clinical study of the histamine H3 receptor antagonist/inverse agonist pitolisant for the treatment of narcolepsy in Japan.

This phase 3 study consists of a multi-institutional double-blind, randomized, placebo-controlled, parallel group-comparison study (Part 1) and an open-label long-term treatment study (Part 2) to assess the efficacy and safety of pitolisant. Please visit the following site for detailed information on the study.

https://jrct.niph.go.jp/en-latest-detail/jRCT2031220432

Pitolisant was developed by Bioprojet. Aculys Pharma has obtained an exclusive license to develop and commercialize it in Japan.

Patients often start suffering from the symptoms of narcolepsy in childhood, adolescence or young adulthood, but aren’t diagnosed to have it until much later due to misdiagnosis, low symptom awareness, or other reasons: The delay in diagnosis is a global challenge.1  The causes and pathophysiology of narcolepsy are largely unknown. In healthy people, neurotransmitters in the brain, such as orexin and histamine, help maintain the regular cycle of daytime wakefulness and nighttime sleep (REM and non-REM sleep), while in patients with narcolepsy, this sleep-wake cycle becomes irregular.2  Due to this irregular sleep-wake cycle, patients with narcolepsy suddenly, and against their will, fall asleep or have difficulty maintaining concentration while engaged in school or work. Some patients also have cataplexy attacks, which are a sudden loss of muscle tone of the whole body or certain voluntary muscles that are triggered by strong emotions, hypnagogic hallucinations (a hallucination that occurs right before falling asleep), and sleep paralysis (“old hag” syndrome).  Different patients have different patterns and severity of symptoms, but these symptoms significantly affect the lifestyles of patients, who often face severe challenges in education or employment.3

Aculys Pharma is committed to bringing this drug to patients with narcolepsy in Japan as early as possible and aims to help achieve a society where people with narcolepsy and their family members live their lives to the fullest potential.

■ About pitolisant

Pitolisant is an antagonist/inverse agonist that selectively binds to the histamine H3 receptor, an autoreceptor located in the presynaptic region of the histamine-containing neurons in the human brain that plays a critical role in regulating sleep and wake rhythm. The drug was created by Paris-based Bioprojet and was approved by the European Medicines Agency (EMA) for the treatment of “narcolepsy with or without cataplexy” in 2016 and for the treatment of “excessive daytime sleepiness associated with obstructive sleep apnea syndrome (OSAS)” in 2021. In the United States, the drug was approved by the Food and Drug Administration (FDA) for the treatment of “excessive daytime sleepiness associated with narcolepsy” in 2019 and “cataplexy associated with narcolepsy” in 2020 and has been available in the clinical setting.

■ About Aculys Pharma, Inc.

Aculys Pharma is a biopharmaceutical company focused on the development and commercialization of innovations in the fields of neurology and psychiatry. Its corporate name was created from the philosophy of serving as a “Catalyst to Access.”  Aiming to act as a bridge for innovative medical care in the field of neuropsychiatry, Aculys Pharma develops and commercializes novel pharmaceuticals and provides innovations for better medical care to patients, their families, healthcare professionals, and society.

Company name: Aculys Pharma, Inc.

Address: 2-14-4 Kitaaoyama, Minato-ku, Tokyo, Japan

Representative: Kazunari Tsunaba

Established: January 2021

URL: https://aculys.com

Information concerning pharmaceutical products (compound under development) contained herein is not intended as advertising or as medical advice but intended for disclosure of management information.

References:

1  Thorpy MJ, Krieger AC. Delayed diagnosis of narcolepsy: characterization and impact. 2014 May;15(5):502-7.

2  Scammell TE. Narcolepsy. NEJM. 2015;373:2654-2662.

3  Scammell TE, Jackson AC, Franks NP, Wisden W, Dauvilliers Y. Histamine: neural circuits and new medications. Sleep. 2019 Jan 1;42(1):zsy183.

Aculys Pharma has entered into a comprehensive collaboration agreement with KNOCK ON THE DOOR to solve social issues related to recurrent epileptic seizures

– Initiating digital transformation (DX) in clinical trial and joint research utilizing real-world data –

Aculys Pharma, Inc. (“Aculys Pharma” Headquarters: Minato-ku, Tokyo; Representative Director and CEO: Kazunari Tsunaba), a company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, announced that it has entered into a comprehensive collaboration  agreement with KNOCK ON THE DOOR, Inc. (“KNOCK ON THE DOOR” Headquarters: Shinjuku-ku, Tokyo; Representative Director: Yasuomi Hayashi), to resolve social issues related to epileptic seizures.

It is said that 0.6 to 1 million people or 5 to 8 in 1000 people suffer from epilepsy* in Japan. With advancements in medical care, many patients with epilepsy are able to take control of their seizures and lead normal social lives by being appropriately diagnosed and treated with anti-epileptic drugs or other treatments. However, about 30 percent of patients are not able to adequately control their seizures- placing a burden on their families/caregivers to have to respond to recurrent seizures1,2.

The cause, symptoms, and severity of epileptic seizures varies widely among patients, and epileptic seizures themselves exhibit diverse characteristics in each patient. Among the diverse seizure types, there are cases in which patients experience seizures that recur many times a day or that do not terminate after a certain period of time. These patients are at an increased risk of brain damage and experiencing a negative impact on their prognosis. Therefore prompt therapeutic interventions are necessary3. However, current mainstream practice, for such patients, has been inefficient, with long ambulance transport times to get them to a medical institution for treatment. On average, it takes 40 minutes from the time a call is placed until the patient is treated with medications by healthcare professionals3. An extensive overseas survey of patients, their families, and physicians reports that recurrent epileptic seizures cause significant emotional, social, and financial burden, not only on patients, but also on their families4.

To realize a society in which patients with recurrent epileptic seizures, along with their families/caregivers can lead their lives without worries, Aculys Pharma is preparing for the development of diazepam intranasal spray in Japan to provide a means to respond to seizures outside of medical institutions5.  Aculys Pharma is also striving to facilitate the creation of an ecosystem that enables communities to respond more rapidly to epileptic seizures by actively utilizing new technologies and services.

With an aim of improving epilepsy medical care, KNOCK ON THE DOOR provides a smartphone app, “nanacara”, co-developed with epilepsy patients, their families and physicians, to record medication compliance and seizure frequency. The app provides a platform service that allows users to record critical information easily and accurately for better medical care and to share it with physicians6.

Aculys has reached a comprehensive collaboration agreement with KNOCK ON THE DOOR as a partner in building an ecosystem.  Through these collaborative efforts, KNOCK ON THE DOOR will develop and provide an e-diary app with specifications for the Aculys’ clinical trial to record information on seizures, physical conditions, and medication administration by the patient’s family.  Aculys Pharma will leverage the know-how that KNOCK ON THE DOOR has to collect accurate and reliable data in a simplified manner.

In parallel with the clinical trial collaboration, the companies are planning to conduct research by using epileptic seizure-related real-world data, accumulated in nanacara, which has already been widely used in the field of epilepsy, to reveal the actual situation and problems around epileptic seizures in Japan, and to utilize the research findings to facilitate a better medical care system for patients with epileptic seizures.

Aculys will continue to contribute to the Japanese society by identifying healthcare issues from a social point of view and finding solutions through actively utilizing new technologies and developing external partnerships.

 

*Epilepsy is a chronic brain disorder in which excessive electrical excitation of nerve cells in the brain leads to symptoms (epileptic seizures) such as disturbed consciousness and seizures.

**A general term for data related to a patient’s health status and the delivery of health care routinely collected from various sources, including claims data, electronic medical records, health checkups, and patient registries. This study utilizes data from nanacara users who gave informed consent for purposes of information usage.

Source :

1 Study on Epidemiological Studies on the Prevalence of Epilepsy, Analysis of Practice and Development of Treatment System-2013

2 Kwan P, MJ Brodie. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314–9.

3 Guidelines for the Treatment of Pediatric Convulsions (Japanese Society for Pediatric Neurology) 2017.

4 Penovich PE, Buelow J, Steinberg, et al. Burden of seizure clusters on patients with epilepsy and caregivers survey of patient, caregiver, and clinician perspectives. The Neurologist. 2017;22:207–214.

5 https://aculys.com/aculys-pharma-signed-an-exclusive-licensing-agreement-with-neurelis-inc-for-the-development-and-commercialization-of-valtoco/

6 https://nanacara.jp/

■About KNOCK ON THE DOOR Inc.

KNOCK ON THE DOOR, Inc. is a venture company that provides platforms for epilepsy treatment” nanacara” and “nanacara for Doctor” under the philosophy of “making patients and their families the light of the world”.  The company provides solutions for challenges surrounding the disease through collaboration with patients with intractable epilepsy, who often suffer rare diseases, and their families, to improve the quality of life of patients and their families.

Company name: KNOCK ON THE DOOR, Inc.

Address: 3F, 2-1 DS, Yahata-cho, Shinjuku-ku, Tokyo

Established in July 2018

URL:  https://knockonthedoor.jp

■ About Aculys Pharma, Inc.

Aculys Pharma is a biopharmaceutical company focused on the development and commercialization of innovations in the fields of neurology and psychiatry. Its corporate name was created from the philosophy of “Catalyst to Access.”  Aimed to act as a bridge for innovative medical care in the field of neuropsychiatry, Aculys Pharma develops and commercializes novel pharmaceuticals and provides innovations for better medical care to patients, their families, healthcare professionals, and society.

Company name: Aculys Pharma, Inc.

Address: 2-14-4 KitaAoyama, Minato-ku,Tokyo, Japan

Representative: Kazunari Tsunaba

Established: Jan 2021

URL: https://aculys.com

 

Information concerning pharmaceutical product (compound under development) contained herein is not intended as advertising or as medical advice, but intended for disclosure of management information.

Aculys Pharma and SUSMED have entered into a contract to conduct the world’s first clinical trial utilizing blockchain technology

– Introducing digital transformation (DX) for monitoring work and reducing new drug development costs –

Aculys Pharma, Inc. (“Aculys Pharma” Headquarters: Minato-ku, Tokyo, President and CEO: Kazunari Tsunaba), a company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, has entered into a contract with SUSMED, Inc., a company that promotes digital medicine, (“SUSMED” Headquarters: Chuo-ku, Tokyo, CEO: Taro Ueno) to conduct the world’s first1 corporate-sponsored clinical trial using blockchain technology.  The clinical trial utilizing this blockchain technology, provided by SUSMED, will be conducted in collaboration with CMIC Co., Ltd., (“CIMIC” Headquarters: Minato-ku, Tokyo, President and CEO: Toru Fujieda), a pioneer in drug development support (CRO), with the cooperation of several medical institutions.

With the sophistication of research and development and the increasing cost of new drug development, improving the efficiency of clinical trials is one of the challenges in the pharmaceutical industry that requires addressing. In such an environment, efficient use of resources and pursuit of efficiency are required. And improving productivity and quality of new drug development is also extremely important for society as a whole. Under these circumstances, Aculys Pharma is working to improve productivity and quality of clinical trials by utilizing AI and digital technologies for the development and commercialization of new drugs.

The clinical trial system developed by SUSMED enables the reduction of data entry work and monitoring work2 by medical institutions by using the SUSMED-patented technology that binds e-worksheets and eCRF using blockchain technology. In addition to publishing multiple medical papers3, the clinical research that SUSMED conducted with the National Cancer Center has been approved by the Cabinet Office regulatory sandbox4. The result of the verification test conducted by the regulatory sandbox was published in the International Medical Journal in June 20205.  With this outcome, The Ministry of Health, Labor and Welfare issued a notice on December 4, 2020 that source data verification (SDV: Source Data Verification) using blockchain technology is permitted as an alternative method under the GCP ministerial ordinance.

CMIC will promote these efforts for attaining an efficient clinical trial by 1) supporting the operation of the system at the medical institution, 2) cooperating with development of the e-worksheet and eCRF, and 3) complementing the functions outside the scope of the system.

This clinical trial which utilizes blockchain technology significantly reduces the number of processes around data entry at medical institutions and SDV compared to conventional methods, and also contributes to reducing the number of required CRA visits to the medical institutions.  In addition, by taking advantage of blockchain technology, it is expected to have the effect of increasing the reliability of the clinical trial data itself.  Through these methods, we aim to improve the efficiency of the clinical trial-related work-streams necessary for new drug development, and to optimize new drug development costs without compromising reliability.

This clinical trial utilizing blockchain technology, which is a pioneering effort to solve medical problems in Japan, is joined by CMIC, Japan’s first CRO company willing to adopt new technologies.  By leveraging the strengths of each of the three companies, we will collaborate to achieve improvements in the quality and efficiency of clinical trials.  These three companies will continue to contribute to Japanese society by identifying medical issues from a social point of view and by actively utilizing new technologies and external partnerships to resolve them.

1 PubMed (https://pubmed.ncbi.nlm.nih.gov/), a medical literature information Data Base, and ClinicalTrials.gov (https: //pubmed.ncbi.nlm.nih.gov/), a clinical trial information Data Base managed by the National Library of Medicine of the National Institutes of Health. https://www.clinicaltrials.gov/), EU Clinical Trials Register (https://www.clinicaltrialsregister.eu/ctr-search/search), a clinical trial information Data Base of the :European Medicines Agency, and SUSMED research based on other research tool.

2 Monitoring work: work to confirm that clinical trials are being conducted properly according to the protocol. Work also includes source data verification by checking clinical trial data by directly browsing the original medical records.

3 Ichikawa et al., 2017, JMIR mHealth uHealth, Motohashi et al., 2019, JMIR

4 A system that established to promote regulatory reform for accelerating business activities using new technologies and business models based on the Act on Special Measures for Productivity Improvement.

5 Hirano et al., 2020, JMIR

Kazunari Tsunaba, President and CEO of Aculys Pharma, Inc., stated as follows.

“We are delighted to be able to conduct a clinical trial utilizing blockchain technology in collaboration with SUSMED and CIMIC as Aculys Pharma strives for providing new therapeutic modalities by making full use of the latest in digital technology.  We expect this pioneering effort of three companies, which aim to improve the quality and efficiency of clinical trials, will realize digital transformation of clinical trial monitoring work and contribute to the optimization of new drug development costs. We will continue to actively introduce new technologies not bound by a conventional framework and aim to solve social issues surrounding Japanese healthcare by collaborating and partnering with external partners.”

Taro Ueno, President and CEO of SUSMED, Inc., stated as follows.

“In the clinical trials conducted in the development of new medical technology, prevention of data tampering and cost efficiency have been issues. While developing therapeutic apps in the healthcare field, we have come to focus on the possibility of using blockchain technology in clinical development and continued research and development.  This time, we are delighted to be able to collaborate with CIMIC to conduct the world’s first clinical trials using blockchain technology in a corporate-sponsored clinical trial of Aculys Pharma, a company that focuses on the development and commercialization of new innovative drugs. We believe that utilization of blockchain technology enables us to realize efficient and reliable clinical development and we also can contribute for optimization and sustainability of future social security.”

Toru Fujieda, President of CMIC Co., Ltd., stated as follows.

“CMIC was established in 1992 as Japan’s first CRO and has supported a number of clinical trials of drug development. This time we are participating in the corporate-sponsored clinical trial of Aculys Pharma with SUSMED. While digitalization will furthermore drive acceleration of process efficiency, we will continue to pursue further improvement of quality and efficiency of clinical trials in monitoring work by utilizing CIMIC’s know-how based on numerous clinical trial experiences over the past 30 years.”

■ About Aculys Pharma, Inc.

Aculys Pharma is a biopharmaceutical company focused on the development and commercialization of innovations in the fields of neurology and psychiatry. Its corporate name was created from the philosophy of “Catalyst to Access.”  Aimed to act as a bridge for innovative medical care in the field of neuropsychiatry, Aculys Pharma develops and commercializes novel pharmaceuticals and provides innovations for better medical care to patients, their families, healthcare professionals, and society.

Company name: Aculys Pharma, Inc.

Address: 2-14-4 KitaAoyama, Minato-ku,Tokyo, Japan

Representative: Kazunari Tsunaba

Established: Jan 2021

URL: https://aculys.com

■About SUSMED, Inc.

SUSMED, Inc. is an R&D-oriented company that promotes digital medicine. In addition to providing clinical development support systems that utilize blockchain technology, SUSMED, Inc. develops digital therapeutics for insomnia and other disorders. SUSMED, Inc. has acquired various patents for medical applications of blockchain technology and digital therapeutics.

Name: SUSMED, Inc.

Address: 3-7-2 Nihonbashi-Honcho, Chuo-ku, Tokyo

CEO: Taro UENO

Founding: February 2016

URL:https://www.susmed.co.jp/en/

■About CMIC Group

CMIC Group was founded in 1992 as the first Contract Research Organization (CRO) in Japan. Today CMIC Group is the largest clinical CRO in Japan with a global footprint, providing comprehensive services in drug development, clinical site management, manufacturing, regulatory consulting and contract sales & marketing solutions. CMIC Group helps pharmaceutical, biotech and medical device companies to enter the Japanese market, to conduct clinical trials in Asia, or to bridge drug development and manufacturing needs in the US, Europe, Japan and broader Asia. CMIC Group has over 7,000 employees and 24 sites globally. For more information about CMIC Group and services, please visit website below.

https://en.cmicgroup.com/

Company name: CMIC Co., Ltd.

Address: Hamamatsucho Bldg., 1-1-1 Shibaura, Minato-ku,Tokyo

Representative: Toru Fujieda

Established: Established in March 1985, opened in 1992

URL:https://www.cmicgroup.com/

Information concerning pharmaceutical product (compound under development) contained herein is not intended as advertising or as medical advice, but intended for disclosure of management information.

Aculys Pharma initiates collaboration with Ubie with the aim of building a “sleep ecosystem”

- a fact-finding survey of patients with sleep disorders to be conducted as a first step -

Aculys Pharma, Inc. (“Aculys Pharma” Headquarters: Minato-ku, Tokyo, Representative Director and CEO: Kazunari Tsunaba), a company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, initiated a fact-finding survey about patients with sleep disorders as part of efforts to build a “sleep ecosystem” for solving sleep-related social issues with Ubie, Inc. (“Ubie” Headquarters: Chuo-ku, Tokyo, co-representative directors: Yoshinori Abe and Kenta Kubo).

The impact of sleep-related problems on Japanese society is enormous. There is also a research result that reports presenteeism (decrease in productivity at work due to health problems) and absenteeism (absence due to health problems) due to lack of sleep cause an economic loss of about 3% of GDP, equivalent to about 15 trillion yen. Compared to other countries, sleeping time of Japanese people is shorter due to lack of correct knowledge about stress and sleep. Therefore, even the “National Health Promotion Movement in the twenty first century (Health Japan 21)” promoted by the government picked up sleep as one of the key themes in attempt to raise awareness.

Problems with sleep disorders are also factors that interfere with proper sleep and daytime awakening. It has been reported that delays in appropriate medical intervention for sleep disorders and complications associated with sleep disorders (cardiovascular diseases, depression, etc.) rather increase overall cost including medical care expenditure. In order to improve the patient’s QoL (quality of life), life prognosis, productivity, and reduce social loss, it is necessary to detect people suspected to suffer sleep disorders and provide appropriate medical care at early stage.

To solve these sleep-related social issues, Aculys Pharma strives to develop a “sleep ecosystem” that provides comprehensive solutions by actively utilizing new technologies and services through working with external partners.

As part of building a “sleep ecosystem”, we have started collaboration with Ubie to conduct a fact-finding survey of patients with obstructive sleep apnea syndrome (OSAS) and narcolepsy. It is considered that the actual situation of these illnesses remains to be unknown as many people have not been examined or diagnosed. Patient survey using the platform provided by Ubie enables to identify issues surrounding patients. We aim to utilize the interviews about sleep using Ubie’s AI technology and objective sleep assessment using digital device in order to formulate programs to solve problems.

Aculys Pharma will continue to contribute to Japanese society by identifying medical issues from a social point of view and actively utilize new technologies and external partnerships for resolving social challenges.

* A general term for sleep disorders such as Insomnia, Sleep Related Breathing Disorders (OSAS, etc.), and Central Disorders of Hypersomnolence (narcolepsy, etc.).

  1. Hafner M et al. Why Sleep Matters-The Economic Costs of Insufficient Sleep. Cambridge, UK: RAND Europe; 2016
  2. OECD (2009), Society at a Glance 2009: OECD Social Indicators, OECD Publishing, Paris.
  3. 2019年 国民健康・栄養調査報告(厚生労働省)
  4. Lyons MM, et al. Global burden of sleep-disordered breathing and its implications. Respirology 2020 Jul;25(7):690-702.
  5. Skaer TL, Sclar DA. Economic implications of sleep disorders. Pharmacoeconomics 2010;28(11):1015–23.
  6. Leger D, Bayon V, Laaban JP, et al. Impact of sleep apnea on economics. Sleep Med Rev 2012;16: 455–62.
  7. Flores NM, Villa KF, Black J, Chervin RD, Witt EA. The humanistic and economic burden of narcolepsy. J Clin Sleep

■ About Ubie, Inc.
Ubie is a Japanese HealthTech Startup founded by a medical doctor and an engineer in 2017. Using AI as its core technology, the company develops and provides AI-powered patient questionnaire which guides patients from symptoms to appropriate medical care, and improves operational efficiency in the medical field. We are promoting the creation of a society in which anyone can access medical care that suits them best.

Office of Japan HQ:601 Fukushima Bldg., 1-5-3 Nihonbashi Muromachi, Chuo Ward, Tokyo, Japan, 103-0022
Established: May 2017
Representative: Yoshinori Abe Co-Founder/CEO, MD Kenta Kubo Co-Founder/CEO, Software Engineer
URL: https://ubie.life

■ About Aculys Pharma, Inc.
Aculys Pharma is a biopharmaceutical company focused on the development and commercialization of innovations in the fields of neurology and psychiatry. Its corporate name was created from the philosophy of “Catalyst to Access.” Aimed to act as a bridge for innovative medical care in the field of neuropsychiatry, Aculys Pharma develops and commercializes novel pharmaceuticals and provides innovations for better medical care to patients, their families, healthcare professionals, and society.
http://aculys.com

Company name: Aculys Pharma, Inc.
Address: 2-14-4 KitaAoyama, Minato-ku,Tokyo, Japan
Representative: Kazunari Tsunaba
Established: Jan 2021
URL: https://aculys.com

Information concerning pharmaceutical product (compound under development) contained herein is not intended as advertising or as medical advice, but intended for disclosure of management information.

Aculys Pharma Closes US$24 Million Series B Financing

Aculys Pharma, Inc. (“Aculys Pharma” Headquarters: Fujisawa City, Kanagawa Prefecture, Representative Director and CEO: Kazunari Tsunaba), a new biopharmaceutical company focused on the development and commercialization of new innovative drugs in the fields of neurology and psychiatry, today announced that it has raised a total of US$24 million in Series B Round with participation by JIC Venture Growth Investments, Mitsubishi UFJ Capital, Spiral Capital as new investors.  Existing investors Vision Pacific LifeSciences Capital I, II (DE) LLC1, HBM Healthcare Investments, Global Founders Capital, Sumitomo Mitsui Trust Investment, and ANRI also participated in the round.  As a result of this capital increase, the cumulative amount raised by the company has reached US$84 million.

Kazunari Tsunaba, Co-founder, Chief Executive Officer and Representative Director of Aculys said,  “Advances in medical care, including new anti-epileptic drugs, have enabled many epilepsy patients and caregivers to lead their daily lives without seizures.2, 3 However, despite proper diagnosis and treatment, there are still patients and their caregivers suffering from recurrent epileptic seizures, and there is still a need for immediate treatment when a seizure emergency occurs outside the medical institution. Beyond seizure control, we believe that we have a lot of work to do such as eliminating misunderstandings and prejudices about epilepsy and seizures, and strengthening social support.  We are deeply grateful to all domestic and overseas investors for their support of our aspiration to create a society where patients and their caregivers can live without fear and anxiety.”

In addition to ongoing development and commercialization of pitolisant for the treatment of sleep disorders, Aculys Pharma will use the funds raised in this Series B round for clinical development and commercial activities for launching the first nasal spray formulation of diazepam in Japan for epileptic seizure emergencies. We will conduct clinical trials in Japan and develop this innovative medicine so that patients who can benefit from this new treatment have access to it as soon as possible. At the same time, we will invest in comprehensive initiatives to reduce the impact of epileptic seizures on the daily lives of patients and their families by facilitating the creation of a community that provides quick access to therapeutic drugs, in the event of a sudden seizure, and through collaboration with external partners to conduct studies to develop a system which enables the prediction of seizures using AI and digital tools. We will also promote educational activities to improve public understanding of epilepsy in our society.

Beyond the development and commercialization of new medicines, Aculys is committed to the patient experience, including the awareness, screening, diagnosis, personalized treatment and resolution of surrounding social issues for patients and their families confronted with neurological and psychiatric disease. The company looks to form comprehensive solutions through cross-sectional partnerships using new technologies to enhance the patient experience.

1  Joint ventures co-owned by Catalys Pacific and SoftBank Vision Fund 2
2  World Health Organization  https://www.who.int/news-room/fact-sheets/detail/epilepsy
3  Ministry of Health, Labour and Welfare  https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000070789_00008.html

About nasal spray (active ingredient: diazepam)

Diazepam has been used as a therapeutic agent for the treatment of epileptic seizure as an injectable for more than 60 years in Japan. It also has a history as a suppository for use by non-medical personnel such as patients and caregivers, outside of medical institutions. In 2020, the U.S. Food and Drug Administration approved Neurelis’ VALTOCO® (diazepam nasal spray) as an acute treatment for intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from an individual’s usual seizure pattern in adult and pediatric patients 6 years of age and older.

About Aculys Pharma, Inc.

Aculys Pharma is a biopharmaceutical company focused on the development and commercialization of innovations in the fields of neurology and psychiatry. Its corporate name was created from the philosophy of “Catalyst to Access.”  Aimed to act as a bridge for innovative medical care in the field of neuropsychiatry, Aculys develops and commercializes novel pharmaceuticals and provides innovations for better medical care to patients, their families, healthcare professionals, and society.

http://www.aculys.com

Company name: Aculys Pharma, Inc.
Address: 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, Japan
Representative: Kazunari Tsunaba
Established: Jan 2021

URL: https://www.aculys.com

Information concerning pharmaceutical product (compound under development) contained herein is not intended as advertising or as medical advice, but intended for disclosure of management information.