Otsuka and Click Therapeutics Announce the U.S. Food and Drug Administration (FDA) Clearance of Rejoyn™, the First Prescription Digital Therapeutic Authorized for the Adjunctive Treatment of Major Depressive Disorder (MDD) Symptoms

PRINCETON, N.J. and NEW YORK, N.Y. (April 1, 2024) – Otsuka Pharmaceutical, Co. Ltd. (Otsuka) and Click Therapeutics, Inc., (Click) announce that the U.S. Food and Drug Administration (FDA) has cleared Rejoyn™ (developed as CT-152), the first prescription digital therapeutic authorized for the treatment of major depressive disorder (MDD) symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD age 22 years and older who are on antidepressant medication. Rejoyn is intended to reduce MDD symptoms.

Rejoyn is a six-week treatment program designed to help enhance cognitive control of emotion through a combination of clinically-validated cognitive emotional training exercises for the brain and brief therapeutic lessons. Unlike wellness apps, the Rejoyn app is a medical device authorized by the FDA for prescription by a healthcare professional.

“Rejoyn represents a novel and exciting adjunctive treatment option to address major depressive disorder (MDD) symptoms that complements the current standard of care,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka. “While traditional approaches are often effective, many are left with only a partial response to treatment. Otsuka has a long, unwavering commitment to addressing the unmet needs of people living with mental illnesses and the clearance of Rejoyn is an example of delivering on that promise. We are deeply grateful to the trial participants, clinicians, and everyone at Otsuka and Click Therapeutics, who helped Rejoyn reach this important milestone.”

The clearance of Rejoyn is based on data from the Mirai study, a 13-week pivotal, multicenter, remote, double-blinded, randomized, controlled trial of 386 participants, aged 22 to 64, diagnosed with MDD who were on antidepressant medication for the treatment of depression. In the trial, patients were randomized to receive either Rejoyn or a sham control app. Individuals treated with Rejoyn showed an improvement in depression symptom severity from baseline. Symptom improvement was consistently observed across multiple patient and clinician-reported scales, including the Montgomery-Åsberg Depression Rating Scale (MADRS), Patient Health Questionnaire nine-item depression scale (PHQ-9), and the Clinical Global Impression – Severity scale (CGI-S). One month after completing the six-week treatment program, participants in the Rejoyn group showed continued improvement. No side effects were assessed as related to Rejoyn during the trial. Full clinical data may be found as part of the Clinician Brief Summary.

Rejoyn offers a novel approach to the treatment of depression symptoms as it is designed to target neural networks affected by depression and is hypothesized to leverage the brain’s inherent neuroplasticity to alter those connections leading to symptom reduction over time. Clinical research has long shown that chemical imbalances are not the only cause of depression, though most common treatments target these neurochemical abnormalities. For some people with depression, the parts of the brain responsible for emotion recognition and processing and the parts responsible for cognition do not communicate properly, making emotional regulation more difficult.¹

“Rejoyn has a neuromodulatory mechanism designed to act like physical therapy for the brain by delivering personalized, consistent brain-training exercises designed to help improve connections in the brain regions affected by depression,” said Brian Iacoviello, Ph.D., assistant professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, scientific advisor at Click Therapeutics and a co-inventor of Emotional Faces Memory Task (EFMT). “When stronger and more balanced connections are created, the regions of the brain responsible for processing and regulating emotions are better able to work together and symptoms of depression can improve.”

Rejoyn introduces clinically-validated cognitive emotional brain training exercises (“Emotional Faces Memory Task” or “EFMT”) that were developed and studied by a team of psychologists, psychiatrists and neuroscientists. These brain exercises are designed to target and help alter those neural connections necessary to appropriately process emotions with the goal of reducing symptoms of depression.

“Only a third of patients diagnosed with depression and who receive antidepressants as their first-line treatment, are successful. These patients need new options that capitalize on proven-effective treatment strategies,” said David Benshoof Klein, co-founder and chief executive officer at Click Therapeutics. “The clearance of Rejoyn signals a fundamental change in how clinicians can treat symptoms of major depressive disorder. It provides hope for those who are looking for new treatment options, especially one that is easily accessible through the device in the palm of your hand.”

Rejoyn requires a prescription from a healthcare provider and is expected to be available for download from app stores for iOS® and Android™ operating systems in the latter half of 2024. To learn more about Rejoyn and sign up for updates regarding its availability, go to www.rejoyn.com. Healthcare providers can visit www.rejoynhcp.com.

INDICATIONand SAFETY INFORMATION forRejoyn^™

INDICATION:

Rejoyn is a prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms as an adjunct to the clinician-managed outpatient care for adult patients with MDD age 22 years and older who are on antidepressant medication. It is intended to reduce MDD symptoms.

SAFETY INFORMATION:

There are no contraindications to using Rejoyn. Rejoyn is not intended to be used as a standalone therapy or a substitute for medication. Patients should continue their current treatment as directed.

Rejoyn does not monitor the patient’s symptoms or clinical status and cannot send or receive alerts or warnings to the prescriber.

Patients should be clearly instructed that if they believe their depression is worsening or if they have feelings or thoughts of harming themselves or others, to contact a healthcare professional, dial 911, or go to the nearest emergency room immediately.

About the Mirai Clinical Study
The indications for use of Rejoyn are supported by the results from the Mirai Trial, a pivotal 13-week multicenter, remote, double-blinded, randomized controlled trial in adult participants diagnosed with MDD who were on antidepressant medication for the treatment of depression. The primary efficacy endpoint was the change from baseline to week six in the MADRS total score. Effectiveness was also evaluated using the PHQ-9 and the CGI-S scale.

In the trial, a total of 386 participants were randomized to receive Rejoyn (194) or a sham control app (192) that resided on the patients’ personal smartphones. The study enrolled patients from 22 to 64 years of age with a current primary diagnosis of MDD based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and who reported an inadequate response to their current antidepressant medication, defined as <50% reduction in depression symptom severity in the current major depressive episode. The study included a 3-week screening period, a 6-week treatment period, and a 4-week extension period.

Participants in both groups received personalized reminders and text messages throughout the study duration to maintain engagement, and trial visits were conducted remotely by video or telephone. Further, all participants were expected to adhere to their app exercises during the treatment period, and adherence was monitored. During the trial, no serious treatment emergent adverse events (TEAEs), or discontinuations due to a TEAE, or deaths occurred in the patients receiving Rejoyn.

About Major Depressive Disorder
According to the World Health Organization, approximately 280 million people in the world have depression, with 21 million people suffering in the United States alone, as reported by the National Institute of Mental Health.^{4, 5} MDD is a condition that often requires a combination of first-line antidepressant medication, talk therapy or psychotherapy, and other adjunctive treatments to alleviate symptoms. Even with available approaches, many patients may not achieve optimal responses to treatment, resulting in an unmet need for new and different treatment modalities.^{, 2, 3, 6, 7}

About Prescription Digital Therapeutics
Digital therapeutics are health software intended to treat or alleviate a disease, disorder, condition, or injury by generating and delivering a medical intervention that has a demonstrable positive therapeutic impact on a patient’s health.⁸ A prescription digital therapeutic (PDT) is a digital therapeutic only available to patients by a prescription from a healthcare provider. PDTs can be used independently or in conjunction with medications, devices, or other therapies to optimize patient care under the guidance of their healthcare provider.⁹As a new modality of treatment, PDTs deliver medical interventions directly to patients from their smartphones using software programs that are subject to clinical evidence requirements and regulatory oversight and are recognized as medical devices by the FDA.

About the Otsuka and Click Therapeutics Collaboration
Otsuka America, Inc. (OAI) and Click Therapeutics, Inc., signed a collaboration agreement in 2019 to develop and commercialize prescription digital therapeutics for treatment of MDD, with the intent to address unmet medical needs among this patient population and to improve outcomes. Rejoyn is the first FDA-cleared treatment resulting from this collaboration.

About Otsuka
Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs.

OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 14.2 billion in 2023.

All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/.

About Click
Click Therapeutics, Inc., develops, validates, and commercializes software as prescription medical treatments for people with unmet medical needs. As a leading innovator of Digital Therapeutics™, we deliver accessible, clinically proven, FDA-regulated prescription treatments to the smartphone in your hand. Our treatments are defined by our commitment to applying technical and scientific rigor and patient-centric design to the development process. This results in uniquely engaging experiences that achieve compelling clinical outcomes for patients seeking new treatment options. We are continuously expanding and refining our shared platform technologies with novel cognitive, behavioral and neuromodulatory mechanisms of action and advanced data-driven tools such as artificial intelligence and machine learning.

Digital therapeutics under development on our platform address diverse areas of therapeutic need, including indications in psychiatry, neurology, oncology, immunology, and cardiometabolic diseases. Consistently named a best place to work, we foster an inclusive, diverse workforce of innovators, clinicians, scientists, researchers, designers, technologists, engineers and more, united in our mission to provide patients everywhere access to safe and effective prescription digital therapeutics.