April 13, 2023

Announcement for Initiation of Phase III Trial ofGlycerol Phenylbutyrate in Urea Cycle Disorders in Japan
OrphanPacific, Inc. (Minato-ku, Tokyo, Japan; hereinafter referred to as “OrphanPacific”)
announces that the first patient has been successfully enrolled in the phase III clinical trial ofglycerol phenylbutyrate (the development code: HPN-100; the brand name in the United Statesand Europe: Ravicti®) in Japanese patients with Urea Cycle Disorders (UCD).
In Japan, both Buphenyl® tablets and granules are currently being prescribed to control theincrease in blood ammonia levels caused by UCD, while in the United States and Europe,
Ravicti®, has been widely used instead of Buphenyl® for the management of UCD patients.
Ravicti® is an oral liquid containing glycerol phenylbutyrate that is tasteless, odorless and easy
to take, and a highly convenient formulation, especially for infants and pediatric patients;
therefore, it has been awaited to become available in Japan as well.
OrphanPacific obtained exclusive rights to develop, manufacture and sell Ravicti® in Japan onMay 2, 2022, from Immedica Pharma AB (Stockholm, Sweden).
This phase III clinical trial is planned to enroll 15 pediatric and adult patients with UCD in Japan.
The primary objective of this study is to evaluate the effectiveness of glycerol phenylbutyrate
in controlling blood ammonia levels compared with that of Buphenyl®. In addition,
pharmacokinetics and safety of glycerol phenylbutyrate will be evaluated as well comparedwith those of Buphenyl® in pediatric and adult patients.

For detailed information on this study (jRCT2071220110), please visit Japan Registry ofClinical Traials.
OrphanPacific will strive to deliver Ravicti® as quickly as possible for patients who are fighting
this intractable disease, UCD and their families.
About Urea Cycle Disorders (UCD)The Urea Cycle is a metabolic pathway that converts toxic ammonia (NH 3) generated in thebody into non-toxic urea mainly in the liver. The UCD is a group of diseases that present withhyperammonemia due to congenital abnormalities in enzymes involved in the Urea Cycle.
Patients with UCD may experience vomiting, poor feeding, tachypnea, convulsions, impaired
consciousness, behavioral disorders, developmental disorders, and sometimes lifethreatening conditions. Most of UCD patients develop in infancy, but some of them arediagnosed only in adulthood. The UCD occurs in 1 per 8,000 to 44,000 people and is one ofthe designated intractable diseases in Japan.
[Reference] Intractable Disease Information Center; Urea Cycle Disorders (DesignatedIntractable Disease 251)https://www.nanbyou.or.jp/entry/4732 (written in Japanese; access as of 10 April. 2023)

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About OrphanPacificOrphanPacific is a Japanese pharmaceutical company that brings new therapeutic drugs topatients with rare diseases through the development, manufacturing and sale of orphan drugs.
The company’s mission is to "deliver smiles and happiness to patients with rare diseases andtheir families." With the determination of "Leave No One Behind", OrphanPacific is actively
working on the development and distribution of drugs for the treatment of rare diseases with avery small number of patients. OrphanPacific is a wholly-owned subsidiary of CMIC Holdings,
a pioneer and leading CRO (Contract Research Organization) in Japan. Making the best useof the CMIC Group’s experience and know-how of development, manufacturing and sales ofdrugs, the company aims to enable as many patients with rare diseases as possible to haveaccess to therapeutic drugs.
＜Contact＞
OrphanPacific, Inc., Corporate Planning Department.
info@orphanpacific.com
Tel.03-6779-8151