News

– This approval follows the recent marketing authorization for IZCARGOTM in the United Arab Emirates –

Hyogo, Japan – October 14, 2026 – JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”), a global specialty biopharmaceutical company dedicated to developing therapies for rare and genetic diseases, today announced that IZCARGO™ (pabinafusp alfa, or JR-141), a blood-brain barrier-penetrating enzyme replacement therapy (ERT) for Hunter syndrome developed using JCR’s proprietary J-Brain Cargo® technology, received conditional marketing authorization in Kuwait.

Kuwait is the second market outside Japan where IZCARGO™ has received approval, following the United Arab Emirates in July 2026. IZCARGO™ was approved and launched in Japan in 2021 and is currently being evaluated in an ongoing global Phase III clinical trial.

JCR has been working to expand access to IZCARGO™ outside of Japan while advancing its global clinical development program. As part of this effort, JCR entered into a marketing and distribution agreement with Taiba Middle East FZ LLC (“Taiba”) and pursued regulatory approval in Kuwait based on the product’s marketing authorization in Japan. Under this agreement, JCR will also seek marketing authorization for IZCARGO™ in countries across the Middle East and North Africa (MENA) region, while Taiba will be responsible for sales and distribution in the relevant territories.

“The approval of IZCARGO™ in Kuwait marks an important advancement in our efforts to broaden access to specialized treatments for rare diseases in the region,” said Dr. Saif Al Hasani, Taiba Group CEO. “Building on the UAE approval, this milestone highlights the value of strong partnerships between regional healthcare organizations and global innovators in translating medical advancements into meaningful progress for patients. At Taiba, we remain focused on supporting sustainable access to innovative therapies and strengthening the region’s capacity to address complex and underserved medical needs.”

“The approval of IZCARGO™ in Kuwait marks an important advancement in our efforts to broaden access to specialized treatments for rare diseases in the region,” said Dr. Saif Al Hasani, Taiba Group CEO. “Building on the UAE approval, this milestone highlights the value of strong partnerships between regional healthcare organizations and global innovators in translating medical advancements into meaningful progress for patients. At Taiba, we remain focused on supporting sustainable access to innovative therapies and strengthening the region’s capacity to address complex and underserved medical needs.”

The impact of this announcement on JCR’s consolidated financial results for this fiscal year (ending March 31, 2027) is expected to be minor.

About the J-Brain Cargo® Platform Technology
JCR Pharmaceuticals has developed a proprietary blood-brain barrier (BBB)-penetrating technology, J-Brain Cargo®, to bring biotherapeutics into the central nervous system (CNS). The first drug developed based on this technology is IZCARGO™ (INN: pabinafusp alfa), which is approved in Japan for the treatment of Hunter syndrome, a lysosomal storage disorder (LSD). With J-Brain Cargo®, JCR seeks to address the unresolved clinical challenges of LSDs by delivering the enzyme to both the body and the brain.

About Hunter Syndrome (Mucopolysaccharidosis Type II, or MPS II)
Hunter syndrome (mucopolysaccharidosis type II, or MPS II) is an X-linked recessive lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase, an enzyme that breaks down complex carbohydrates called glycosaminoglycans (GAGs, also known as mucopolysaccharides) in the body. Hunter syndrome, which affects an estimated 2,000-3,000 individuals worldwide (according to JCR research), gives rise to a wide range of somatic and neurological symptoms. The current standard of care for Hunter syndrome is enzyme replacement therapy. Central nervous system symptoms related to MPS II have been unmet medical needs so far.

About Pabinafusp Alfa
Pabinafusp alfa (JR-141) is a recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in subjects with Hunter syndrome. It incorporates J-Brain Cargo®, JCR’s proprietary blood-brain barrier (BBB)-penetrating technology, to cross the BBB through transferrin receptor-mediated transcytosis, and its uptake into cells is mediated through the mannose-6-phosphate receptor. This novel mechanism of action is expected to make pabinafusp alfa effective against the central nervous system (CNS) symptoms of Hunter syndrome.

In pre-clinical trials, JCR has confirmed both high-affinity binding of pabinafusp alfa to transferrin receptors and passage across the BBB into neuronal cells. In addition, JCR has confirmed enzyme uptake in various brain tissues. The company has also confirmed a reduction of substrate accumulation in the CNS and peripheral organs in an animal model of Hunter syndrome.1,2

In several clinical trials of pabinafusp alfa, JCR obtained evidence of reducing heparan sulfate (HS) concentrations in the cerebrospinal fluid (CSF), a biomarker for assessing effectiveness against CNS symptoms; these results were consistent with those obtained in pre-clinical studies.3 Clinical studies have also demonstrated the positive effects of pabinafusp alfa on CNS symptoms.4,5,6

Pabinafusp alfa was approved in Japan by the Ministry of Health, Labour and Welfare and marketed since May 2021 under the brand name “IZCARGO™ I.V. Infusion 10mg.”

Important Safety Information

INDICATION:
IZCARGO™ is indicated for the treatment of mucopolysaccharidosis type II (MPS II), which is also known as Hunter syndrome. IZCARGO™ is approved in Japan, the United Arab Emirates (UAE), and Kuwait.

CONTRAINDICATION:
IZCARGO™ is contraindicated in patients with a history of anaphylactic shock to its components.

WARNINGS AND PRECAUTIONS
Warnings
Since serious anaphylaxis and shock may occur with use of IZCARGO™, adequate emergency measures should be made ready for execution before initiation of administration, and the patient should be closely monitored during and after the administration. If a serious infusion associated reaction (IAR) occurs, administration of IZCARGO™ should be discontinued, and appropriate actions should be taken.
When IZCARGO™ is administered to patients with severe respiratory failure or acute respiratory disease, an IAR may lead to acute exacerbation of symptoms. A patient’s condition should be closely monitored, and appropriate actions should be taken as needed.

Precautions for Use
IZCARGO™ is a protein medicinal product and may cause anaphylactic shock, for which close monitoring is required. If any signs of anaphylaxis are noted, discontinue the infusion, and take appropriate actions. Considering the onset of such symptoms, emergency measures should be made ready for execution.
IZCARGO™ may cause IARs such as headache, chills, syncope, fatigue, dizziness, pyrexia, rash, erythema, urticaria, or other symptoms. If an IAR occurs, reduce the rate or temporarily discontinue the infusion, and initiate appropriate drug treatment (e.g., corticosteroids, antihistamines, antipyretic analgesics, anti-inflammatory drugs) or emergency procedures (e.g., oxygen administration, securing of airway, adrenaline administration). Premedication with antihistamines, corticosteroids, etc., should be considered for the subsequent infusion of IZCARGO™.

ADVERSE REACTIONS:
The most commonly reported adverse reactions were pyrexia and urticaria.

About Taiba Middle East FZ LLC
Taiba is a regional leader in the marketing, distribution, and commercialization of orphan and rare disease therapies across the Middle East and North Africa (MENA). With two decades of trusted collaboration with clinicians, hospitals, and global partners.

Taiba combines deep regional expertise with robust commercial execution—from regulatory approvals and patient access programs to strategic partnerships and long-term brand lifecycle management. The company connects healthcare systems with breakthrough treatments through early access and commercialization initiatives. Driven by a mission to close the treatment gap.

Taiba empowers medical institutions with cutting-edge solutions and exceptional service, ensuring patients with unmet medical needs gain timely and sustainable access to life-changing therapies. Please visit: http://www.taibarare.com/.

About JCR Pharmaceuticals Co., Ltd.
JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level.

Cautionary Statement Regarding Forward-Looking Statements
This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future.

References

1. Sonoda, et al. A blood-brain-barrier-penetrating anti-human transferrin receptor antibody fusion protein for neuronopathic mucopolysaccharidosis II. Mol. Ther. 2018; 26(5): 1366-1374.
2. Morimoto, et al. Clearance of heparin sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice. Mol. Ther. 2021; 29(5): 1853-1861.
3. Okuyama, et al. Iduronate-2-sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial. Mol Ther. 2020; 27(2): 456-464.
4. Okuyama, et al. A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II. Mol Ther. 2021; 29(2): 671-679.
5. Giugliani, et al. Iduronate-2-sulfatase fused with anti-human transferrin receptor antibody, pabinafusp alfa, for treatment of neuronopathic and non-neuronopathic mucopolysaccharidosis II: Report of a phase 2 trial in Brazil. Mol Ther. 2021; 29(7): 2378-2386.
6. Giugliani, et al. Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II; an Integrated Analysis of Preclinical and Clinical Data. Int. J. Mol. Sci. 2021, Volume 22, Issue 20, 10938.

Contact:
JCR Pharmaceuticals Co., Ltd.
Corporate Communications / IR Office
ir-info@jp.jcrpharm.com

– JR-141 is a potentially transformative therapy designed to deliver enzymes to the brain and peripheral tissues to treat neuronopathic and somatic symptoms of Hunter syndrome through intravenous administration

– JCR is conducting a global Phase III clinical trial evaluating JR-141 in Hunter syndrome

– Italfarmaco will exclusively commercialize JR-141 in the United States, Europe, and Latin America upon regulatory approval

Milan, Italy and Hyogo, Japan – October 2, 2026 – Italfarmaco S.p.A. (“Italfarmaco”) and JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”) today announced an exclusive license agreement to develop and commercialize JR-141 in the United States, Europe, and Latin America (“licensed territories”) upon regulatory approval. JR-141 is a blood-brain barrier (BBB) penetrating enzyme replacement therapy currently in Phase III (NCT04573023) evaluation as a treatment of Hunter syndrome (also known as mucopolysaccharidosis type II or MPS II). Approved and launched in Japan in 2021 as IZCARGO™ (INN: pabinafusp alfa), JCR and Italfarmaco seek to obtain regulatory approval for JR-141 from the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), and the Brazilian Health Regulatory Agency (ANVISA).

Following regulatory approvals by the FDA, EMA, MHRA and ANVISA, Italfarmaco will commercialize and distribute the product in the licensed territories, while JCR will retain responsibility for manufacturing JR-141 upon marketing authorizations. JCR will receive upfront, milestone and royalty payments, in addition to revenues associated with product supply.

JR-141 is a next-generation recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in individuals with Hunter syndrome. JR-141 was developed using J-Brain Cargo®, JCR’s proprietary BBB-penetration technology. J-Brain Cargo® is engineered to transport the therapeutic enzyme across the BBB to directly reach the brain and address both the somatic and neuronopathic symptoms of the disease, which can lead to progressive cognitive decline.

This agreement expands the relationship between JCR and Italfarmaco, which entered into an exclusive license agreement in December 2025 for the commercialization of givinostat in Japan, a treatment for Duchenne muscular dystrophy, together with a strategic partnership agreement for rare disease therapies.

“We are pleased to enter into this strategic agreement with Italfarmaco and collaborate with an ideal global commercialization partner as we work toward our goal of delivering JR-141 to people living with Hunter syndrome around the world,” said Hiroyuki Sonoda, Ph.D., President and Chief Scientific Officer of JCR Pharmaceuticals. “Italfarmaco has expertise in developing and commercializing therapies worldwide, and we look forward to working with Italfarmaco to make JR-141 available to patients outside Japan as soon as possible. This agreement extends our commitment to the partnership with Italfarmaco, developing therapies for rare and genetic diseases for patients around the globe.”

“This agreement marks an important milestone in the relationship between Italfarmaco and JCR Pharmaceuticals and reflects a shared commitment to advancing innovative therapies for people living with rare and genetic diseases,” said Francesco Di Marco, Chief Executive Officer of Italfarmaco Group. “By bringing together JCR’s pioneering expertise in blood-brain barrier technologies and Italfarmaco’s global capabilities in rare disease development and commercialization, we are creating a strong foundation to accelerate innovation for underserved patient communities.”

“Building on the success of our existing collaboration in Duchenne muscular dystrophy, this agreement further strengthens our partnership and reinforces our shared ambition to be a leading force in the rare and genetic disease field,” said Antonio Nardi, Vice President and Head of Business & Portfolio Development of Italfarmaco. “Alongside our trusted partner, we look forward to advancing our mission of delivering transformative treatments to the patients and families who need them most.”

The upfront payment under this agreement has been incorporated into JCR’s consolidated earnings forecast for the fiscal year ending March 31, 2027.

About the J-Brain Cargo® Platform Technology
JCR Pharmaceuticals has developed a proprietary blood-brain barrier (BBB)-penetrating technology, J-Brain Cargo®, to bring biotherapeutics into the central nervous system (CNS). The first drug developed based on this technology is IZCARGO™ (INN: pabinafusp alfa), which is approved in Japan for the treatment of Hunter syndrome, a lysosomal storage disorder (LSD). With J-Brain Cargo®, JCR seeks to address the unresolved clinical challenges of LSDs by delivering the enzyme to both the body and the brain.

About Hunter Syndrome (Mucopolysaccharidosis Type II, or MPS II)
Hunter syndrome (mucopolysaccharidosis type II, or MPS II) is an X-linked recessive lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase, an enzyme that breaks down complex carbohydrates called glycosaminoglycans (GAGs, also known as mucopolysaccharides) in the body. Hunter syndrome, which affects an estimated 2,000-3,000 individuals worldwide (according to JCR research), gives rise to a wide range of somatic and neurological symptoms. The current standard of care for Hunter syndrome is enzyme replacement therapy, which does not address the central nervous system-related symptoms of this lysosomal disease.

About JR-141
JR-141 (pabinafusp alfa) is a recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in subjects with Hunter syndrome. It incorporates J-Brain Cargo®, JCR’s proprietary blood-brain barrier (BBB)-penetrating technology, to cross the BBB through transferrin receptor-mediated transcytosis, and its uptake into cells is mediated through the mannose-6-phosphate receptor. This novel mechanism of action is expected to make pabinafusp alfa effective against the central nervous system (CNS) symptoms of Hunter syndrome.

In pre-clinical trials, JCR has confirmed both high-affinity binding of pabinafusp alfa to transferrin receptors and passage across the BBB into neuronal cells. In addition, JCR has confirmed enzyme uptake in various brain tissues. The company has also confirmed a reduction of substrate accumulation in the CNS and peripheral organs in an animal model of Hunter syndrome.1,2

In several clinical trials of pabinafusp alfa, JCR obtained evidence of reducing heparan sulfate (HS) concentrations in the cerebrospinal fluid (CSF), a biomarker for assessing effectiveness against CNS symptoms; these results were consistent with those obtained in pre-clinical studies.3 Clinical studies have also demonstrated the positive effects of pabinafusp alfa on CNS symptoms.4,5,6

Pabinafusp alfa was approved in Japan by the Ministry of Health, Labour and Welfare and marketed since May 2021 under the brand name “IZCARGO™ I.V. Infusion 10mg.” It was also approved in the United Arab Emirates (UAE) in 2026.

Important Safety Information

INDICATION:
IZCARGO™ is indicated for the treatment of mucopolysaccharidosis type II (MPS II), which is also known as Hunter syndrome. IZCARGO™ is approved in Japan and the United Arab Emirates (UAE).

CONTRAINDICATION:
IZCARGO™ is contraindicated in patients with a history of anaphylactic shock to its components.

WARNINGS AND PRECAUTIONS:
Warnings
Since serious anaphylaxis and shock may occur with use of IZCARGO™, adequate emergency measures should be made ready for execution before initiation of administration, and the patient should be closely monitored during and after the administration. If a serious infusion associated reaction (IAR) occurs, administration of IZCARGO™ should be discontinued, and appropriate actions should be taken.

When IZCARGO™ is administered to patients with severe respiratory failure or acute respiratory disease, an IAR may lead to acute exacerbation of symptoms. A patient’s condition should be closely monitored, and appropriate actions should be taken as needed.

Precautions for Use

IZCARGO™ is a protein medicinal product and may cause anaphylactic shock, for which close monitoring is required. If any signs of anaphylaxis are noted, discontinue the infusion, and take appropriate actions. Considering the onset of such symptoms, emergency measures should be made ready for execution.

IZCARGO™ may cause IARs such as headache, chills, syncope, fatigue, dizziness, pyrexia, rash, erythema, urticaria, or other symptoms. If an IAR occurs, reduce the rate or temporarily discontinue the infusion, and initiate appropriate drug treatment (e.g., corticosteroids, antihistamines, antipyretic analgesics, anti-inflammatory drugs) or emergency procedures (e.g., oxygen administration, securing of airway, adrenaline administration). Premedication with antihistamines, corticosteroids, etc., should be considered for the subsequent infusion of IZCARGO™.

ADVERSE REACTIONS:
The most commonly reported adverse reactions were pyrexia and urticaria.

Prescribing information, indications, contraindications, warnings, and adverse reactions may differ by jurisdiction. Healthcare professionals should consult the locally approved prescribing information.

About Italfarmaco S.p.A.
Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production and commercialization with proven success in multiple therapeutic areas including oncology, gynecology, neurology, cardiovascular disease and rare diseases. Italfarmaco’s rare disease unit includes programs in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythemia vera.

About JCR Pharmaceuticals Co., Ltd.
JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level.

Cautionary Statement Regarding Forward-Looking Statements
This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future.

References

1. Sonoda, et al. A blood-brain-barrier-penetrating anti-human transferrin receptor antibody fusion protein for neuronopathic mucopolysaccharidosis II. Mol. Ther. 2018; 26(5): 1366-1374.
2. Morimoto, et al. Clearance of heparin sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice. Mol. Ther. 2021; 29(5): 1853-1861.
3. Okuyama, et al. Iduronate-2-sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial. Mol Ther. 2020; 27(2): 456-464.
4. Okuyama, et al. A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II. Mol Ther. 2021; 29(2): 671-679.
5. Giugliani, et al. Iduronate-2-sulfatase fused with anti-human transferrin receptor antibody, pabinafusp alfa, for treatment of neuronopathic and non-neuronopathic mucopolysaccharidosis II: Report of a phase 2 trial in Brazil. Mol Ther. 2021; 29(7): 2378-2386.
6. Giugliani, et al. Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II; an Integrated Analysis of Preclinical and Clinical Data. Int. J. Mol. Sci. 2021, Volume 22, Issue 20, 10938.

Contact:

Media enquiries – Italfarmaco:
Gretchen Schweitzer / Adolfo Luna | +49 (0) 151 626 74395 | italfarmaco@trophic.eu

Other enquiries – Italfarmaco:
Samantha Parker | Patient Advocacy and Communications Lead | RDEnquiries@italfarmacogroup.com

Investors & Media – JCR Pharmaceuticals Co., Ltd.:
Corporate Communications
ir-info@jp.jcrpharm.com

– The study aims to evaluate the safety, tolerability, and preliminary efficacy of JR-446 for the treatment of people with MPS IIIB, for which there is no approved therapy –

Tokyo and Hyogo, Japan – September 11, 2026 – MEDIPAL HOLDINGS CORPORATION (TSE 7459, MEDIPAL) and JCR Pharmaceuticals Co., Ltd. (TSE 4552, JCR) announced today that the first participant has been dosed in the global Phase I/II trial of JR-446 for mucopolysaccharidosis type IIIB (Sanfilippo syndrome type B; “MPS IIIB”). JR-446 is a blood-brain barrier-penetrating α-N-acetylglucosaminidase developed by JCR using its proprietary J-Brain Cargo® technology. MEDIPAL holds commercialization rights for JR-446 outside Japan.

MPS IIIB is a lysosomal storage disorder that causes severe central nervous system impairment. This ultra-rare disease is estimated to affect approximately 500 to 1,000 people worldwide,1 and there is currently no approved treatment.

“Dosing the first patient in this Phase I/II clinical trial is an important milestone for the MPS IIIB community, as there is no approved treatment for this devastating and life limiting lysosomal storage disorder that impacts patients’ neurocognitive development, independence, and quality of life,” said Dr. Irene Chang, Principal Investigator, Associate Professor of Pediatrics, Section of Biochemical Genetics, Division of Medical Genetics, at the University of California, San Francisco (UCSF). “Patients and families affected by this condition continue to face significant unmet medical needs, and we are encouraged to take this next step in evaluating the potential of this investigational therapy. We are grateful to the patients, caregivers, and study teams whose commitment made this milestone possible, and we are hopeful it may bring meaningful improvements in the quality of life for individuals living with MPS IIIB and their families.”

In September 2023, MEDIPAL and JCR entered into a licensing agreement for the commercialization of JR-446 for MPS IIIB outside Japan and a co-development and commercialization agreement in Japan.2 Under this agreement, MEDIPAL holds exclusive worldwide commercialization rights, excluding Japan, with the right to sublicense. On behalf of MEDIPAL, JCR is leading the global Phase I/II trial and development activities as the sponsor.

The global, multicenter, open-label trial is being conducted in patients with MPS IIIB under six years of age. Further information is available at ClinicalTrials.gov under identifier NCT07640984.

Nonclinical studies of JR-446 have demonstrated effects on symptoms associated with MPS IIIB. A separate Phase I/II trial, JR-446-101, is ongoing in Japan under the companies’ co-development agreement. In 2025, JR-446 received orphan drug designation in the United States, the European Union, and Japan.

MEDIPAL and JCR remain committed to advancing JR-446 with the goal of bringing a new treatment option to people with MPS IIIB as quickly as possible.

About Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome Type B)

Mucopolysaccharidosis type IIIB, or Sanfilippo syndrome type B, is an autosomal recessive disease caused by pathogenic mutations in the NAGLU gene, encoding a lysosomal enzyme involved in the degradation of heparan sulfate. With the accumulation of heparan sulfate in the central nervous system in the brain, individuals with this condition present rapid neurological decline, including sleep disorders, loss of speech, and behavioral changes, which may significantly affect the quality of life of patients and their families.

About the J-Brain Cargo® Platform Technology

JCR Pharmaceuticals has developed a proprietary blood-brain barrier (BBB)-penetrating technology, J-Brain Cargo®, to bring biotherapeutics into the central nervous system (CNS). The first drug developed based on this technology is IZCARGO™ (INN: pabinafusp alfa), which is approved in Japan and the United Arab Emirates for the treatment of a lysosomal storage disorder (LSD). With J-Brain Cargo®, JCR and MEDIPAL seek to address the unresolved clinical challenges of LSDs by delivering the enzyme to both the body and the brain.

About MEDIPAL HOLDINGS CORPORATION

MEDIPAL is a holding company which controls, administers and supports the operating activities of companies in which it holds shares in the Prescription Pharmaceutical Wholesale Business; the Cosmetics, Daily Necessities and OTC Pharmaceutical Wholesale Business; and the Animal Health Products and Food Processing Raw Materials Wholesale and Related Business, and conducts business development for the MEDIPAL Group. For more information, visit https://www.medipal.co.jp/english/.

About JCR Pharmaceuticals Co., Ltd.

JCR Pharmaceuticals Co., Ltd. is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. JCR continues to build upon our 50-year legacy in Japan while expanding its global footprint into the US, Europe, and Latin America. JCR’s innovative therapies address conditions like growth disorder, MPS II, Fabry disease, acute graft-versus-host disease, and renal anemia. JCR is also developing treatments for rare diseases like MPS I, MPS II, MPS IIIA and B, and more.

Cautionary Statement Regarding Forward-Looking Statements
This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future.

References

1. Based on data from JCR’s own investigations, referring to the Ministry of Health, Labour and Welfare’s public research.
2. Press release on the licensing agreement for JR-446 between MEDIPAL and JCR (September 28, 2023).

Contacts

MEDIPAL HOLDINGS CORPORATION
Public Relations Department
TEL: (+81)-3-3517-5171

JCR Pharmaceuticals Co., Ltd.
Corporate Communications
E-mail: ir-info@jp.jcrpharm.com

Hyogo, Japan – September 10, 2026 – JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”) sponsored and participated in “Relay For Life of Ashiya,” held in Ashiya, Hyogo, on September 5 and 6. The community charity event is organized by local volunteers and managed by the Relay for Life Kansai Executive Committee and the Japan Cancer Society under license from the American Cancer Society.

Relay For Life brings communities together to support people living with cancer and their families. Funds raised through sponsorships and donations support Japan Cancer Society initiatives including research into new treatments and drug development, free cancer counseling, and efforts to encourage cancer screening. JCR continues to support the event through its sponsorship and participation.

This year, approximately 50 JCR employees and family members from across the company joined the Relay Walk and Candlelight Run. Walking through the night toward dawn, they reflected on what it means for patients to face cancer every day as they ran and walked forward together, one step at a time.

Employees shared reflections such as: “Taking part gave me many new insights and much to learn. It was an invaluable opportunity to gain a firsthand sense of the thoughts and feelings of patients, their families and supporters, and the warmth of the connections among them.” “Running through the night was tough, but the encouragement all around the venue kept me going, one step at a time. I was glad to run even one kilometer farther and contribute more to the fundraising effort.”

JCR will continue to take on difficult healthcare challenges beyond rare disease, while strengthening ties with local communities and contributing to society.

About Relay For Life

Relay For Life began in 1985, when a surgeon in the United States ran around a track for 24 hours to raise donations for the American Cancer Society. His effort symbolized the reality that people with cancer face their illness every hour of every day. What started as a single act of solidarity has
grown into a global movement that inspires courage and hope by bringing people together to walk, talk, and share. Today, Relay For Life is held in approximately 1,700 locations across 37 countries worldwide.
In Japan, Relay For Life continues to expand nationwide, with approximately 52 events scheduled in 2026. Ashiya has officially hosted the event as an overnight gathering since 2007, and this year marks its 20th edition under the theme, “This is where I took a step forward. This is where I meet you again.”
For more information, please visit the official website (Japanese only):
Relay For Life of Ashiya: https://relayforlife.jp/ashiya/.

About JCR Pharmaceuticals Co., Ltd.

JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level.

Contact:
JCR Pharmaceuticals Co., Ltd.
Corporate Communications / IR Office
ir-info@jp.jcrpharm.com

– This marketing authorization is the first for IZCARGOTM outside of Japan –

Hyogo, Japan – July 21, 2026 – JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”), a global specialty biopharmaceutical company dedicated to developing therapies for rare and genetic diseases, today announced that IZCARGOTM (pabinafusp alfa, or JR-141), a blood-brain barrier-penetrating enzyme replacement therapy (ERT) for Hunter syndrome developed using JCR’s proprietary J-Brain Cargo® technology, received marketing authorization in the United Arab Emirates (UAE).

This marks the first marketing authorization for IZCARGOTM outside of Japan. IZCARGOTM was approved and launched in Japan in 2021 and is currently being evaluated in an ongoing global Phase III clinical trial.

JCR has been working to expand access to IZCARGOTM outside of Japan while advancing its global clinical development program. As part of this effort, JCR entered into a marketing and distribution agreement with Taiba Middle East FZ LLC (“Taiba”) and pursued regulatory approval in the UAE based on the product’s marketing authorization in Japan. Under this agreement, JCR will also seek marketing authorization for IZCARGOTM in countries across the MENA region, while Taiba will be responsible for sales and distribution in the relevant territories.

“We are very pleased to announce the approval of IZCARGOTM in the UAE,” said Hiroyuki Sonoda, Ph.D., President and Chief Scientific Officer of JCR Pharmaceuticals. “This is an important milestone for JCR, as it represents the first approval of IZCARGOTM outside of Japan. We look forward to working with Taiba to bring this therapy to more patients with Hunter syndrome and to continue expanding access to IZCARGOTM internationally.”

We are pleased to announce the first approval of IZCARGOTM in the MENA region in collaboration with JCR,” said Dr. Saif Al Hasani, Taiba group CEO. “This partnership reflects our shared commitment to supporting patients affected by Hunter disease and other rare conditions. IZCARGOTM brings a unique perspective by focusing on both innovation and accessibility, ensuring that meaningful solutions can reach those who need them. Together with JCR, we look forward to contributing to the advancement of rare disease care in the region”.

The impact of this announcement on JCR’s consolidated financial results for this fiscal year (ending March 31, 2027) is expected to be minor.

About the J-Brain Cargo® Platform Technology
JCR Pharmaceuticals has developed a proprietary blood-brain barrier (BBB)-penetrating technology, J-Brain Cargo®, to bring biotherapeutics into the central nervous system (CNS). The first drug developed based on this technology is IZCARGOTM (INN: pabinafusp alfa), which is approved in Japan for the treatment of Hunter syndrome, a lysosomal storage disorder (LSD). With J-Brain Cargo®, JCR seeks to address the unresolved clinical challenges of LSDs by delivering the enzyme to both the body and the brain.

About Hunter Syndrome (Mucopolysaccharidosis Type II, or MPS II)
Hunter syndrome (mucopolysaccharidosis type II or MPS II) is an X-linked recessive lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase, an enzyme that breaks down complex carbohydrates called glycosaminoglycans (GAGs, also known as mucopolysaccharides) in the body. Hunter syndrome, which affects an estimated 2,000-3,000 individuals worldwide (according to JCR research), gives rise to a wide range of somatic and neurological symptoms. The current standard of care for Hunter syndrome is enzyme replacement therapy. Central nervous system symptoms related to MPS II have been unmet medical needs so far.
About Pabinafusp Alfa

Pabinafusp alfa (JR-141) is a recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase, the enzyme that is missing or malfunctioning in subjects with Hunter syndrome. It incorporates J-Brain Cargo®, JCR’s proprietary blood-brain barrier (BBB)-penetrating technology, to cross the BBB through transferrin receptor-mediated transcytosis, and its uptake into cells is mediated through the mannose-6-phosphate receptor. This novel mechanism of action is expected to make pabinafusp alfa effective against the central nervous system (CNS) symptoms of Hunter syndrome.

In pre-clinical trials, JCR has confirmed both high-affinity binding of pabinafusp alfa to transferrin receptors and passage across the BBB into neuronal cells. In addition, JCR has confirmed enzyme uptake in various brain tissues. The company has also confirmed a reduction of substrate accumulation in the CNS and peripheral organs in an animal model of Hunter syndrome1,2.

In several clinical trials of pabinafusp alfa, JCR obtained evidence of reducing heparan sulfate (HS) concentrations in the cerebrospinal fluid (CSF), a biomarker for assessing effectiveness against CNS symptoms; these results were consistent with those obtained in pre-clinical studies3. Clinical studies have also demonstrated the positive effects of pabinafusp alfa on CNS symptoms4,5,6.

Pabinafusp alfa was approved in Japan by the Ministry of Health, Labour and Welfare and marketed since May 2021 under the brand name “IZCARGOTM I.V. Infusion 10mg.”

Important Safety Information

INDICATION:
IZCARGOTM is indicated for the treatment of mucopolysaccharidosis type II (MPS II), which is also known as Hunter syndrome. IZCARGOTM is approved in Japan and the UAE.

CONTRAINDICATION:
IZCARGOTM is contraindicated in patients with a history of anaphylactic shock to its components.

WARNINGS AND PRECAUTIONS:
Warnings
Since serious anaphylaxis and shock may occur with use of IZCARGOTM, adequate emergency measures should be made ready for execution before initiation of administration, and the patient should be closely monitored during and after the administration. If a serious infusion associated reaction (IAR) occurs, administration of IZCARGOTM should be discontinued, and appropriate actions should be taken.

When IZCARGOTM is administered to patients with severe respiratory failure or acute respiratory disease, an IAR may lead to acute exacerbation of symptoms. A patient’s condition should be closely monitored, and appropriate actions should be taken as needed.

Precautions for Use
IZCARGOTM is a protein medicinal product and may cause anaphylactic shock, for which close monitoring is required. If any signs of anaphylaxis are noted, discontinue the infusion, and take appropriate actions. Considering the onset of such symptoms, emergency measures should be made ready for execution.

IZCARGOTM may cause IARs such as headache, chills, syncope, fatigue, dizziness, pyrexia, rash, erythema, urticaria, or other symptoms. If an IAR occurs, reduce the rate or temporarily discontinue the infusion, and initiate appropriate drug treatment (e.g., corticosteroids, antihistamines, antipyretic analgesics, anti-inflammatory drugs) or emergency procedures (e.g., oxygen administration, securing of airway, adrenaline administration). Premedication with antihistamines, corticosteroids, etc., should be considered for the subsequent infusion of IZCARGOTM.

ADVERSE REACTIONS:
The most commonly reported adverse reactions were pyrexia and urticaria.

About Taiba Middle East FZ LLC
Taiba is a regional leader in the marketing, distribution, and commercialization of orphan and rare disease therapies across the Middle East and North Africa (MENA). With two decades of trusted collaboration with clinicians, hospitals, and global partners.
Taiba combines deep regional expertise with robust commercial execution—from regulatory approvals and patient access programs to strategic partnerships and long-term brand lifecycle management, the company connects healthcare systems with breakthrough treatments through early access and commercialization initiatives. Driven by a mission to close the treatment gap.
Taiba empowers medical institutions with cutting-edge solutions and exceptional service, ensuring patients with unmet medical needs gain timely and sustainable access to life-changing therapies. please visit http://www.taibarare.com/.

About JCR Pharmaceuticals Co., Ltd.
JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level.

Cautionary Statement Regarding Forward-Looking Statements
This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future.

References
1: Sonoda, et al. A blood-brain-barrier-penetrating anti-human transferrin receptor antibody fusion protein for neuronopathic mucopolysaccharidosis II. Mol. Ther. 2018; 26(5): 1366-1374.
2: Morimoto, et al. Clearance of heparin sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice. Mol. Ther. 2021; 29(5): 1853-1861.
3: Okuyama, et al. Iduronate-2-sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial. Mol Ther. 2020; 27(2): 456-464.
4: Okuyama, et al. A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II. Mol Ther. 2021; 29(2): 671-679.
5: Giugliani, et al. Iduronate-2-sulfatase fused with anti-human transferrin receptor antibody, pabinafusp alfa, for treatment of neuronopathic and non-neuronopathic mucopolysaccharidosis II: Report of a phase 2 trial in Brazil. Mol Ther. 2021; 29(7): 2378-2386.
6: Giugliani, et al. Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II; an Integrated Analysis of Preclinical and Clinical Data. Int. J. Mol. Sci. 2021, Volume 22, Issue 20, 10938.

Contact:
JCR Pharmaceuticals Co., Ltd.
Corporate Communications / IR Office
ir-info@jp.jcrpharm.com