PRINCETON, N.J. and Redwood City, Calif. – October 11, 2018 – Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Proteus Digital Health (Proteus) today announce the signing of an expanded global collaboration agreement that will strengthen the relationship between the two companies for the further development and commercialization of a portfolio of medicines including the ABILIFY MYCITE® (aripiprazole tablets with sensor) offering, which received NDA approval from the U.S. Food and Drug Administration in November 2017. This arrangement reinforces both companies’ continued commitment to provide new advancements in digital medicine products and care models to address the needs of patients suffering from severe mental illness. As part of the expanded collaboration, Otsuka made $88 million in related equity and other payments to Proteus. The expanded agreement covers the development and commercialization of digital medicines over the next five years.

“We are pleased to continue to focus on opportunities to further integrate digital medicines into healthcare eco-systems to provide value-added outcomes for patients suffering from unmet medical needs in the mental health field,” stated Kabir Nath, President and CEO, Otsuka North America Pharmaceutical Business Division, Otsuka America, Inc. “Our expanding collaboration with Proteus is a cornerstone of this strategy, and further enables us to serve the mental health community by developing additional innovative technology solutions.”

A collaborative team comprised of Otsuka and Proteus employees will be dedicated to commercial development and market coordination for the ABILIFY MYCITE System, software integration and standardization, manufacturing and supply chain integration, and coordination. This includes the joint development of an expanded portfolio of digital medicines consisting of other therapies such as atypical antipsychotics used in the treatment of serious mental illness integrated with Proteus sensors. The parties will also work on the joint development of next generation product features and sensor capabilities to expand the potential of digital medicine offerings.

“This commitment to a broad, inter-operable platform is the core reason for us to expand our collaboration with Otsuka in mental health,” said Andrew Thompson, President and CEO of Proteus Digital Health. “This expanded collaboration is a great opportunity to bring novel digital medicine solutions to mental health patients.”

About Otsuka

Otsuka Pharmaceutical 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 for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and has research programs 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 Pharmaceutical is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 46,000 people worldwide and had consolidated sales of approximately USD 11.1 billion in 2017.

All Otsuka stories start by taking the road less travelled. Learn more about Otsuka Pharmaceutical Company on its global website at https://www.otsuka.co.jp/en. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on Twitter at @OtsukaUS.

About Proteus

Proteus Digital Health® is enabling a new category of pharmaceuticals: Digital Medicines. These include widely used drugs, formulated so they communicate when they have been ingested; a wearable patch that detects medicines and captures physiologic response; mobile applications to support patient self-care and physician decision-making; and data analytics to serve the needs of health system managers. The company has more than 450 issued patents that protect this enabling technology, and regulatory clearances in the U.S., European Union and China.

Proteus Digital Health is privately held by investors that include Carlyle, Essex Woodlands, Kaiser Permanente®, Medtronic®, Novartis®, Otsuka, and ON Semiconductor®. Further information is available at: www.proteus.com. Connect with us on Twitter @ProteusDH.

About the ABILIFY MYCITE® System

ABILIFY MYCITE® (aripiprazole tablets with sensor) was approved by the Food and Drug Administration (FDA) for adults in the United States as the first drug-device combination product intended to track drug ingestion, for the treatment of schizophrenia, treatment of bipolar I disorder for acute manic and mixed episodes and maintenance therapy, and the adjunctive treatment of major depressive disorder. ABILIFY MYCITE has not been shown to improve patient compliance or for use in modifying aripiprazole dosage. It should not be used in “real-time” or during an emergency, because detection may be delayed or not occur. The ABILIFY MYCITE System provides an objective summary of drug ingestion over time, to help enhance collaboration with healthcare providers who treat patients with certain serious mental illnesses. Only functions related to tracking drug ingestion have been evaluated or approved by FDA. Please see About the ABILIFY MYCITE® System and IMPORTANT SAFETY INFORMATION for ABILIFY MYCITE below:

The ABILIFY MYCITE System is composed of the following components:

• An aripiprazole tablet embedded with an Ingestible Event Marker (IEM) sensor. This IEM sensor is the size of a grain of sand (1 mm) and is made up of ingredients found in food. The IEM sensor activates when in contact with stomach fluid and communicates to a wearable sensor, called the MYCITE Patch. The IEM sensor is then eliminated from the body.
• The MYCITE Patch detects and records the date and time of the ingestion of the tablet, as well as certain physiological data such as activity level, and communicates this and the tablet ingestion data to the MYCITE APP on a compatible mobile device.
• The MYCITE APP allows patients to review their objective medication ingestion and daily activity level, as well as enter their mood and rest if they wish to do so. They can also invite others to view their data.
• Web-based dashboards are provided to healthcare providers, and caregivers. These dashboards give the healthcare provider the ability to display the individual’s drug ingestion patterns over time. With patient consent, patient-selected caregivers can also access this information, as well as the individual’s daily activity level and self-reported mood and rest.

The ABILIFY MYCITE System is intended to track if ABILIFY MYCITE has been taken. It can take 30 minutes to 2 hours to detect ingestion of the tablet. Sometimes the system might not detect that the medication has been taken. If the MYCITE APP does not indicate that the ABILIFY MYCITE tablet was taken, do not repeat the dose. Only functions related to tracking drug ingestion have been evaluated or approved by FDA.

The impact of the ABILIFY MYCITE System on treatment adherence has not been demonstrated. Some factors, such as connectivity, transmitter malfunction, or device availability, may impact the consistency and reliability of data detection, collection and transmission.

Please visit www.ABILIFYMYCITE.com for more information.

INDICATIONS and IMPORTANT SAFETY INFORMATION for
ABILIFY MYCITE® (aripiprazole tablets with sensor)

INDICATIONS

ABILIFY MYCITE, a drug-device combination product comprised of aripiprazole tablets embedded with an Ingestible Event Marker (IEM) sensor intended to track drug ingestion, is indicated in adults for the:

• Treatment of schizophrenia
• Treatment of bipolar I disorder as monotherapy and as adjunct to lithium or valproate for:
• Acute treatment of manic and mixed episodes
• Maintenance treatment
• Adjunctive treatment of major depressive disorder

Limitations of Use: ABILIFY MYCITE has not been shown to improve patient compliance or for use in modifying aripiprazole dosage. It should not be used in “real-time” or during an emergency, because detection may be delayed or not occur.

IMPORTANT SAFETY INFORMATION

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death (1.6 to 1.7 times) compared to placebo-treated patients. ABILIFY MYCITE is not approved for the treatment of patients with dementia-related psychosis.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults. Those on antidepressant therapy should be monitored closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. The safety and effectiveness of ABILIFY MYCITE have not been established in pediatric patients.

Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in clinical trials of elderly patients with dementia-related psychosis treated with aripiprazole.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs, including ABILIFY MYCITE. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of ABILIFY MYCITE, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and in total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation. If antipsychotic treatment is withdrawn, TD may remit, partially or completely. Prescribing should be consistent with the need to minimize TD.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes mellitus should be regularly monitored for worsening of glucose control; those with risk factors for diabetes (e.g., obesity, family history of diabetes), should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

• Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
• Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking aripiprazole. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping ABILIFY MYCITE if such urges develop.

Orthostatic Hypotension: ABILIFY MYCITE may cause orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue ABILIFY MYCITE at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Seizures: ABILIFY MYCITE should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: ABILIFY MYCITE may impair judgment, thinking, or motor skills. Instruct patients to avoid operating hazardous machinery, including automobiles, until they are certain ABILIFY MYCITE does not affect them adversely.

Body Temperature Regulation: Use ABILIFY MYCITE with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with ABILIFY MYCITE. Use caution in patients at risk for aspiration pneumonia.

Dosage Adjustments and Cytochrome P450 Considerations: For patients with schizophrenia and bipolar I disorder taking ABILIFY MYCITE who are:

• Known CYP2D6 poor metabolizers, administer half the recommended dose
• Known CYP2D6 poor metabolizers taking concomitant strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin), administer a quarter the recommended dose.
• Taking strong CYP2D6 (e.g., quinidine, fluoxetine, paroxetine) or CYP3A4 inhibitors, administer half the recommended dose.
• Taking strong CYP2D6 and CYP3A4 inhibitors, administer a quarter the recommended dose. When co-administered drug is withdrawn, adjust ABILIFY MYCITE dosage to its original level.
• Taking strong CYP3A4 inducers (e.g., carbamazepine, rifampin), double recommended dose over 1 to 2 weeks. When co-administered drug is withdrawn, reduce ABILIFY MYCITE dosage to original level over 1 to 2 weeks.

Commonly Observed Adverse Reactions (incidence ≥5% and at least twice that for placebo) in adult patients:

• Schizophrenia: akathisia
• Bipolar mania (monotherapy): akathisia, sedation, restlessness, tremor, and extrapyramidal disorder
• Bipolar mania (adjunctive therapy with lithium or valproate): akathisia, insomnia, and extrapyramidal disorder
• Major depressive disorder (adjunctive treatment to antidepressant therapy): akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Skin Irritation for MYCITE Patch: Symptoms of skin irritation localized at the site of the MYCITE Patch may occur. In clinical studies, 12.4% of patients (n=61) experienced skin rashes at the site of patch placement.

Pregnancy: Neonates exposed to antipsychotic drugs, including ABILIFY MYCITE, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. Consider the benefits and risks of ABILIFY MYCITE and possible risks to the fetus when prescribing ABILIFY MYCITE to a pregnant woman. Advise pregnant women of potential fetal risk. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ABILIFY MYCITE during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.

Lactation: Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, effects on the breastfed infant, or effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for ABILIFY MYCITE and any potential adverse effects on the infant or from the underlying maternal condition.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1‑800‑438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

About the Proteus Digital Health® Ingestible Sensor and Wearable Sensor Patch

The Proteus ingestible sensor and wearable sensor patch have been approved by the Food and Drug Administration (FDA) for use in the United States, CE marked per the Medical Device Directive for use in the European Union and approved by the China Food and Drug Administration (CFDA) for use in China. More information is available at www.proteus.com.

Otsuka Media Contacts

In U.S.
Lucy Abreu
Corporate Communications
Otsuka America Pharmaceutical, Inc.
lucy.abreu@otsuka-us.com
+1 609-535-9052

Outside U.S.
Jeffrey Gilbert
Leader, Pharmaceutical PR
Otsuka Pharmaceutical, Co., Ltd.
gilbert.jeffrey@otsuka.co.jp
+81 3 6361 7379, +81 80 8728 6039

Proteus Digital Health Media Contact

Emily Fox
Corporate Communications
Proteus Digital Health
efox@proteus.com
+1 408 425 7097