JCR Pharmaceuticals

– Strategic partnership, announced in July 2025, utilizes JCR’s J-Brain Cargo® to develop a novel blood-brain barrier-penetrating therapy targeting a pathological driver of Alzheimer’s disease

– Option exercise puts Acumen’s Enhanced Brain Delivery (EBD™) program on track for IND filing in mid-2027

Hyogo, Japan – June 17, 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 Acumen Pharmaceuticals, Inc. (NASDAQ: ABOS) exercised its exclusive option to develop, manufacture, and commercialize, on a global basis, up to two candidates for development in the treatment of Alzheimer’s disease (AD), enabled by JCR’s proprietary blood-brain barrier (BBB)-penetrating technology platform, J-Brain Cargo®.

The partnership, announced in July 2025, focuses on developing a BBB-penetrating treatment for AD that combines JCR’s J-Brain Cargo® with Acumen’s amyloid beta oligomer (AβO)-selective antibodies, which target toxic soluble AβOs, a key pathological driver in the onset and progression of AD. The collaborative program aims to demonstrate the feasibility of applying J-Brain Cargo® in delivering sabirnetug, Acumen’s targeted immunotherapy drug candidate, and other AβO-selective antibodies across the BBB to slow the progression of AD pathology. Earlier this year, Acumen presented non-clinical data from a mouse model of AD at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders, which demonstrated that using AβO-selective antibodies with J-Brain Cargo® technology increased brain exposure while preserving target engagement as demonstrated by AβO selectivity. Acumen plans to file an investigational new drug application for this program in mid-2027.

Under the terms of the agreement, JCR will receive an option payment with Acumen’s decision to exercise its exclusive option to develop, manufacture, and commercialize, on a global basis, up to two candidates from the collaboration. JCR will also be eligible to receive future milestone payments of up to USD 40 million related to development, and up to USD 515 million related to sales, for a total of up to USD 555 million (approximately JPY83.2 billion converted at the exchange rate of JPY 150 to USD). In addition, JCR is entitled to receive tiered royalties based on net sales for any products that emerge from the collaboration.

“We’re pleased that our strategic partner, Acumen Pharmaceuticals, opted to exercise its exclusive option to develop, manufacture, and commercialize on a global basis up to two candidates for the treatment of Alzheimer’s disease,” said Hiroyuki Sonoda, Ph.D., President and Chief Scientific Officer of JCR Pharmaceuticals. “Acumen continues to progress the collaborative development program in Alzheimer’s disease, and the non clinical data that Acumen reported earlier this year are truly encouraging. By combining our J-Brain Cargo® platform with Acumen’s novel, AβO-selective antibodies, we aim to overcome the challenge of delivering biologics to the brain to potentially improve the ability to treat AD safely and effectively.”

“As we build on the strength of our sabirnetug program, we’re pleased to exercise our exclusive option to develop, manufacture, and commercialize on a global basis up to two candidates for the treatment of Alzheimer’s disease,” said Daniel O’Connell, Chief Executive Officer of Acumen Pharmaceuticals. “By pairing our AβO-selective antibody expertise with JCR’s blood-brain barrier-penetrating technology, J-Brain Cargo®, we have the potential to deliver a next-generation therapeutic which could further expand and enhance the treatment paradigm for people living with Alzheimer’s disease. We look forward to sharing updates when they are available.”

AD is a progressive neurodegenerative disorder affecting more than 50 million people globally and is a leading form of dementia. One of its defining pathological hallmarks is the accumulation of Aβ in the brain, which are believed to trigger a cascade of events leading to neuronal damage, cognitive decline, and memory loss.1 Delivering biologics across the BBB remains a fundamental obstacle to effectively treating the disease.

J-Brain Cargo® is JCR’s proprietary platform that enables the systemic delivery of biotherapeutics to the central nervous system (CNS) through a mechanism known as receptor-mediated transcytosis. The technology has been clinically validated with IZCARGO™, the first approved drug in Japan to use the platform, for the treatment of a lysosomal storage disorder with CNS involvement. With broad potential to deliver a wide range of biologic therapies across the BBB, J-Brain Cargo® is a versatile platform for advancing treatments for complex CNS conditions, including neurodegenerative diseases. The J-Brain Cargo® technology platform has a well-established safety profile through several non-clinical studies, clinical trials and marketing experience in Japan.

The impact of this announcement on JCR’s consolidated financial results for the fiscal year ending March 31, 2027, has already been factored into the current earnings forecast.

About Alzheimer’s Disease
Alzheimer’s disease is a progressive neurodegenerative disorder affecting more than 50 million people globally and is a leading cause of dementia. One of its defining pathological features is the accumulation of amyloid-beta (Aβ) in the brain, and increasing evidence highlights soluble Aβ oligomers as a particularly neurotoxic species that are thought to trigger a cascade of events leading to neuronal damage, cognitive decline, and memory loss.1

About the J-Brain Cargo® Platform Technology
JCR Pharmaceuticals has developed a proprietary blood-brain barrier-penetrating technology, J-Brain Cargo®, to bring biotherapeutics into the central nervous system. The first drug developed based on this technology is IZCARGO™ (INN: pabinafusp alfa), which was approved in Japan for the treatment of 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 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.

About Sabirnetug (ACU193)
Sabirnetug (ACU193) is a humanized monoclonal antibody (mAb) discovered and developed based on its selectivity for soluble amyloid beta oligomers (AβOs), which are a highly toxic and pathogenic form of Aβ, relative to Aβ monomers and amyloid plaques. Soluble AβOs have been observed to be potent neurotoxins that bind to neurons, inhibit synaptic function, and induce neurodegeneration. By selectively targeting toxic soluble AβOs, sabirnetug aims to address the hypothesis that soluble AβOs are an early and persistent underlying cause of the neurodegenerative process in Alzheimer’s disease (AD). Sabirnetug has been granted Fast Track designation for the treatment of early AD by the U.S. Food and Drug Administration and is currently being evaluated in a Phase 2 study in patients with early AD.

About Acumen Pharmaceuticals, Inc.
Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company developing a novel therapeutic that targets toxic soluble amyloid beta oligomers (AβOs) for the treatment of Alzheimer’s disease (AD). Acumen’s scientific founders pioneered research on AβOs, which a growing body of evidence indicates are early and persistent triggers of Alzheimer’s disease pathology. Acumen is currently focused on advancing its investigational product candidate, sabirnetug (ACU193), a humanized monoclonal antibody that selectively targets toxic soluble AβOs, in its ongoing Phase 2 clinical trial ALTITUDE-AD (NCT06335173) in early symptomatic AD, following positive results in its Phase 1 trial INTERCEPT-AD. Acumen is investigating a subcutaneous formulation of sabirnetug using Halozyme’s proprietary ENHANZE® drug delivery technology. Acumen is also collaborating with JCR Pharmaceuticals to develop an Enhanced Brain Delivery™ (EBD™)-enabled therapy for Alzheimer’s disease utilizing a transferrin-receptor-targeting blood-brain barrier-penetrating technology. The company is headquartered in Newton, Mass. For more information, visit www.acumenpharm.com.

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.

Reference
1. Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J. Amyloid-beta: a crucial factor in Alzheimer’s disease. Med Princ Pract. 2015;24(1):1-10. www.doi.org/10.1159/000369101.

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

Hyogo, Japan – June 8, 2026 – JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”), a global specialty biopharmaceutical company dedicated to developing therapies for rare and genetic diseases, announced today that it presented new clinical data in a poster session at the 18th International Symposium on MPS and Related Lysosomal Diseases, which was held June 4-7, 2026, in Florence, Italy.

“Due to the protective blood-brain barrier, lysosomal storage disorders historically have been challenging to treat due to the inability to deliver a therapy into the central nervous system. With our J-Brain Cargo® platform technology, we have the potential to address the progressive neurological symptoms associated with these rare and life-limiting diseases, many of which have inadequate treatment options or no approved therapies available,” said Hiroyuki Sonoda, Ph.D., President and Chief Scientific Officer of JCR Pharmaceuticals. “The data presented at this symposium demonstrate the safety and efficacy evidence of JR 171 (lepunafusp alfa) in people with mucopolysaccharidosis type I (MPS I) and highlight its potential. We look forward to sharing additional data from our J-Brain Cargo® platform technology as they are available. We wish to thank all of the patients who have participated in our clinical programs and their families, clinical investigators, and other partners who continue to support our work.”

New Clinical Data Presentation

Three-Year safety and pharmacodynamics of lepunafusp alfa (JR-171) in patients with mucopolysaccharidosis type I (MPS-I): Results from a phase I/II trial and extension study (Presentation Number: 63)
Lead Author: Paul Harmatz, M.D. (UCSF Benioff Children’s Hospital, Oakland, CA)

Researchers reported on three years of data describing safety and pharmacodynamics of lepunafusp alfa (JR-171) in patients with mucopolysaccharidosis type I (MPS I) who were treated in a Phase I/II trial plus a three-year extension study (NCT04227600 and NCT04453085). Patients with MPS I were randomized to weekly intravenous lepunafusp alfa at a “Low” (2.0 mg/kg; n=6) or a “High” (4.0 mg/kg; n=8) dose and followed for three years. Enrollment was open to all MPS I phenotypes (Hurler [n=7], Hurler-Scheie [n=5], Scheie [n=2]); one Low-dose Hurler patient did not continue in the extension study.

Both the High‑ and Low‑dose cohorts demonstrated a favorable safety and tolerability profile, with compliance exceeding 90% in both groups. Overall, six patients experienced serious adverse events (SAEs) [5/8 in the High dose group, 1/5 in the Low dose group]. Of the 8 serious treatment-emergent adverse events (TEAEs), none were attributed to lepunafusp alfa. Adverse events of special interest — specifically anaphylaxis or infusion associated reactions — were uncommon, occurring in fewer than 5% of participants across both dose groups.

By Week 12, cerebrospinal fluid-heparan sulfate (CSF-HS) decreased in all patients. In the High dose group, CSF-HS decreases remained stable during the three-year study period in most patients; partial rebound was observed in one patient. In the Low dose group, two patients, both with Hurler syndrome, had a subsequent rebound in HS levels. Rebound did not correlate with presence/absence of antibodies.

The somatic symptoms (including serum HS levels, and liver and spleen volume) remained stable, or improved, in patients in both doses who received previous laronidase and decreased in the treatment-naïve patient.

With three years of follow-up, researchers concluded that weekly lepunafusp alfa is safe and well tolerated in a broad spectrum of patients with MPS I, with no serious TEAEs attributable to the study drug. Pharmacodynamic response of CSF-HS demonstrates that lepunafusp alfa crosses the blood-brain barrier (BBB), with a trend toward greater reduction in CSF-HS in the High dose cohort (4mg/kg). The long-term safety and clinical efficacy warrants evaluation in a larger clinical trial.

Encore Clinical Data Presentations

The following encore presentations provide additional evidence and context for the use of JR-141 (pabinafusp alfa) in the treatment of MPS II and were shared at the 22nd Annual WORLDSymposium™ 2026 (February 2-6, 2026).

Sustained cognitive and adaptive behavior outcomes of long-term treatment with pabinafusp alfa in patients with severe or attenuated mucopolysaccharidosis type II (Presentation Number: 61)
Lead Author: Roberto Giugliani, M.D., Ph.D. (Federal University of Rio Grande do Sul, Brazil)

In a longitudinal, pooled, post hoc analysis of patients with MPS II receiving pabinafusp alfa across five open-label trials with up to five years of follow-up, researchers reported on sustained cognitive and adaptive behavior outcomes of long-term treatment with pabinafusp alfa in patients with severe or attenuated MPS II. Researchers concluded that long-term treatment with pabinafusp alfa was well tolerated and associated with stabilization or continued skill acquisition in many patients with severe or attenuated MPS II, suggesting that, with timely initiation prior to the onset of irreversible neurodegeneration, treatment with pabinafusp alfa may provide a benefit to patients with MPS II.

Long-term somatic efficacy of pabinafusp alfa across a broad spectrum of age groups and phenotypes in patients with mucopolysaccharidosis type II (Presentation Number: 62)
Lead Author: Ana Maria Martins, M.D., Ph.D. (Federal University of São Paulo)

In a longitudinal, pooled, post hoc analysis of patients with MPS II receiving pabinafusp alfa in open-label trials with up to five years of follow-up, researchers reported on the somatic effects of pabinafusp alfa in a heterogenous population of patients with MPS II who initiated treatment at different ages. Researchers concluded that long-term treatment with pabinafusp alfa was well tolerated and provided positive somatic effects to a broad spectrum of severe and attenuated patients with MPS II.

About the International Symposium on MPS and Related Lysosomal Diseases
The International Symposium on MPS and Related Lysosomal Diseases brings together healthcare professionals, researchers, and industry leaders to accelerate progress in mucopolysaccharidoses (MPS) and related lysosomal storage disorders through collaborative innovation. We unite diverse perspectives to advance early diagnosis through cutting-edge technologies, develop revolutionary therapies, and ensure equitable global access to care. Our mission is to foster the next generation of rare disease advocates and professionals while creating sustainable partnerships that transform scientific breakthroughs into real-world improvements in patient outcomes worldwide. For more information, please visit https://mps2026.com/.

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 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 Mucopolysaccharidosis Type I (Hurler, Hurler-Scheie, Scheie Syndrome)
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder (LSD) caused by a deficiency of α-L-iduronidase, an enzyme that breaks down glycosaminoglycans (mucopolysaccharides) in the body. The current worldwide prevalence of MPS I is estimated to be approximately 3,000-4,000 (according to JCR internal research). MPS I gives rise to a wide range of somatic and neurological symptoms. A major limitation of current enzyme replacement therapy (ERT) is that it does not address central nervous system (CNS) symptoms because of the enzyme’s inability cross the blood brain barrier (BBB). MPS I is the only LSD in which hematopoietic stem cell transplantation (HSCT) is part of the standard of case for the severe form of the disease. Significant unmet medical need persists in all forms of MPS I.

About JR-171
JR-171 (lepunafusp alfa) is a recombinant fusion protein of an antibody against the human transferrin receptor and α-L-iduronidase, the enzyme that is missing or malfunctioning in patients with mucopolysaccharidosis type I (MPS I).^1,2 By crossing the blood brain-barrier (BBB) through transferrin receptor mediated transcytosis, it is expected to be effective against central nervous system (CNS) signs and symptoms of the disease thereby addressing a significant unmet need for the treatment of MPS I. JR-171 previously was granted Fast Track designation by the US Food and Drug Administration (FDA).

About Mucopolysaccharidosis Type II (Hunter Syndrome)
Mucopolysaccharidosis type II (MPS II, or Hunter syndrome) 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 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.^3,4

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.⁵ Clinical studies have also demonstrated the positive effects of pabinafusp alfa on CNS symptoms.^6,7,8

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.”

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: Kida S, et al. Enzyme replacement with transferrin receptor-targeted α-L-iduronidase rescues brain pathology in mucopolysaccharidosis I mice. Mol Ther Methods Clin Dev. 2023; 29: 439-449.
2: Harmatz P, et al. α-L-iduronidase fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa) for mucopolysaccharidosis type I: A phase 1/2 trial. Mol Ther. 2024;32(3): 609-618.
3: 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.
4: 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.
5: 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.
6: 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.
7: 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.
8: 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:
Investors & Media:
JCR Pharmaceuticals Co., Ltd.
Corporate Communications
ir-info@jp.jcrpharm.com

Hyogo, Japan – May 28, 2026 – JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”), a global specialty biopharmaceutical company dedicated to developing therapies for rare and genetic diseases, announced today that it will present new clinical data in a poster session at the 18th International Symposium on MPS and Related Lysosomal Diseases, being held June 4-7 in Florence, Italy. The poster presentation will demonstrate the potential benefits of the investigational therapy, JR-171 (lepunafusp alfa), and of J-Brain Cargo®, JCR’s proprietary technology that delivers medicine across the blood-brain barrier (BBB) for the treatment of lysosomal storage disorders and other neurodegenerative diseases.

The details of the new clinical data presentation are listed below:

Title: Three-Year safety and pharmacodynamics of lepunafusp alfa (JR-171) in patients with mucopolysaccharidosis type I (MPS-I): Results from a phase I/II trial and extension study
Lead Author: Paul Harmatz, M.D. (UCSF Benioff Children’s Hospital, Oakland, CA)
Presentation Number: 63

In addition, researchers will also share the following encore presentations on JR-141 (pabinafusp alfa) in the treatment of MPS II that were disclosed at the 22nd Annual WORLDSymposium™ 2026 (February 2-6, 2026).

Title: Sustained cognitive and adaptive behavior outcomes of long-term treatment with pabinafusp alfa in patients with severe or attenuated mucopolysaccharidosis type II
Lead Author: Roberto Giugliani, M.D., Ph.D. (Federal University of Rio Grande do Sul, Brazil)
Presentation Number: 61

Title: Long-term somatic efficacy of pabinafusp alfa across a broad spectrum of age groups and phenotypes in patients with mucopolysaccharidosis type II
Lead Author: Ana Maria Martins, M.D., Ph.D. (Federal University of São Paulo)
Presentation Number: 62

Attendees who would like to receive more information about JCR Pharmaceuticals can visit JCR’s on-site conference booth (#5).

The full program can be found on the International Symposium on MPS and Related Lysosomal Diseases website at https://mps2026.com/program. All posters will be available during the Networking Break and Poster Viewing sessions throughout the entire symposium.

About the International Symposium on MPS and Related Lysosomal Diseases
The International Symposium on MPS and Related Lysosomal Diseases brings together healthcare professionals, researchers, and industry leaders to accelerate progress in mucopolysaccharidoses (MPS) and related lysosomal storage disorders through collaborative innovation. We unite diverse perspectives to advance early diagnosis through cutting-edge technologies, develop revolutionary therapies, and ensure equitable global access to care. Our mission is to foster the next generation of rare disease advocates and professionals while creating sustainable partnerships that transform scientific breakthroughs into real-world improvements in patient outcomes worldwide. For more information, please visit https://mps2026.com/.

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 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 Mucopolysaccharidosis Type I (Hurler, Hurler-Scheie, Scheie Syndrome)
Mucopolysaccharidosis I (MPS I) is an autosomal recessive lysosomal storage disorder (LSD) caused by a deficiency of α-L-iduronidase, an enzyme that breaks down glycosaminoglycans (mucopolysaccharides) in the body. The current worldwide prevalence of MPS I is estimated to be approximately 3,000-4,000 (according to JCR internal research). MPS I gives rise to a wide range of somatic and neurological symptoms. A major limitation of current enzyme replacement therapy (ERT) is that it does not address central nervous system (CNS) symptoms because of the enzyme’s inability cross the blood-brain barrier (BBB). MPS I is the only LSD in which hematopoietic stem cell transplantation (HSCT) is part of the standard of case for the severe form of the disease. Significant unmet medical need persists in all forms of MPS I.

About JR-171
JR-171 (lepunafusp alfa) is a recombinant fusion protein of an antibody against the human transferrin receptor and α-L-iduronidase, the enzyme that is missing or malfunctioning in patients with mucopolysaccharidosis type I (MPS I).1,2 By crossing the blood brain-barrier (BBB) through transferrin receptor mediated transcytosis, it is expected to be effective against central nervous system (CNS) signs and symptoms of the disease thereby addressing a significant unmet need for the treatment of MPS I. JR-171 previously was granted Fast Track designation by the US Food and Drug Administration (FDA).

About Mucopolysaccharidosis Type II (Hunter Syndrome)
Mucopolysaccharidosis type II (MPS II, or Hunter syndrome) 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 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 IZCARGOTM 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.3,4

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.5 Clinical studies have also demonstrated the positive effects of pabinafusp alfa on CNS symptoms.6,7,8

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.”

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.

References
1: Kida S, et al. Enzyme replacement with transferrin receptor-targeted α-L-iduronidase rescues brain pathology in mucopolysaccharidosis I mice. Mol Ther Methods Clin Dev. 2023; 29: 439-449.
2: Harmatz P, et al. α-L-iduronidase fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa) for mucopolysaccharidosis type I: A phase 1/2 trial. Mol Ther. 2024; 32(3): 609-618.
3: 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.
4: 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.
5: 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.
6: 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.
7: 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.
8: 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.

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Hyogo, Japan – May 26, 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 its “Invention of a Technology for Brain Delivery of Biopharmaceuticals” received “The Prize of the Minister of Education, Culture, Sports, Science, and Technology (The Prize of the MEXT Minister)” at the 2026 National Commendation for Invention, organized by the Japan Institute of Invention and Innovation.

The National Commendation for Invention recognizes outstanding inventions, devices, and designs that have made significant contributions, as well as those expected to make substantial future contributions. Held annually with funds granted by the Imperial Household, the commendation aims to contribute to the advancement of science and technology and the development of industry in Japan.

“The Prize of the MEXT Minister” is a special prize presented in the first prize category to inventions that demonstrate outstanding scientific and technological advancement and have achieved significant practical results.

The Prize recognizes JCR’s invention of a drug delivery technology designed to deliver biologic medicines to the brain. The brain is protected by the blood–brain barrier (BBB), which restricts the delivery of therapeutic agents and has long been a major challenge in the treatment of central nervous system (CNS) disorders. JCR’s proprietary J-Brain Cargo® technology, Patent No. JP6797148 and related patents, represents an important advance in addressing this challenge. In Japan, the technology has already been put into practical use in a treatment for a lysosomal storage disorder, which is a rare disease. Global development is also underway, with potential applications being explored in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, as well as neuroinflammatory diseases and CNS tumors.

JCR will continue to advance research and development to meet the needs of patients and families facing diseases with limited or no effective treatment options, and to open new possibilities in medicine.

Overview of the Prize
Prize Recipient (Title at the time of this prize)
Hiroyuki Sonoda, Ph.D.
Representative Director, President, Chief Scientific Officer
JCR Pharmaceuticals Co., Ltd.

Kenichi Takahashi, Ph.D.
Scientific Expert Fellow, Director, Advanced Biopharmaceutical Research Institute
JCR Pharmaceuticals Co., Ltd.

Name of Prize -winning Invention
Invention of a Technology for Brain Delivery of Biopharmaceuticals

Overview of the Prize -winning Invention
This invention is a drug delivery technology designed to transport biologic medicines to the brain.

It relates to a novel antibody targeting the transferrin receptor (TfR) and to medicines that use this antibody to transport therapeutic agents across the BBB.

The brain is protected by the BBB, which prevents harmful substances from entering the CNS. However, this barrier also makes brain delivery difficult and has long been a major challenge in developing treatments for CNS disorders. In particular, large-molecule biologics, including enzymes and antibodies, typically have limited ability to cross the BBB.

To address this, the invention leverages a physiological mechanism by which the brain takes up iron, an essential nutrient. Iron is transported into the brain via TfR, which is expressed on the surface of endothelial cells lining cerebral blood vessels. The antibody used in this invention is engineered to bind TfR and undergo BBB transport through the iron uptake pathway, without disrupting the receptor’s physiological function.

As an initial practical application of this invention, a medicine combining the antibody with a therapeutic enzyme was developed and received marketing approval in Japan in 2021. This demonstrated that the antibody-based technology can function as an approved BBB crossing drug delivery platform.

The drug delivery technology of this invention is applicable not only to proteins such as enzymes and antibodies, but also to a wide range of other modalities, including oligonucleotides, lipid nanoparticles, and gene therapies. Based on this applicability, research and development of new medicines using the invention is being pursued through collaborations with partners in Japan and overseas.

By enabling biologics to reach the brain across the BBB, this invention provides a practical drug delivery approach for CNS disorders, where effective delivery of therapeutic agents to the brain has remained a significant unmet medical need.

Fig.1 Brain Distribution of J‑Brain Cargo®, a Blood-Brain Barrier-Crossing Technology Developed through This Invention

Fig.2 Mechanism by Which a Drug Applied with J‑Brain Cargo® Crosses the Blood–Brain Barrier

About the J-Brain Cargo® Platform Technology
JCR Pharmaceuticals has developed a proprietary blood-brain barrier-penetrating technology J-Brain Cargo®, to bring biotherapeutics into the central nervous system. The first drug developed based on this technology is IZCARGOTM (INN: pabinafusp alf) and was approved in Japan for the treatment of a lysosomal storage disorder.
J-Brain Cargo® | JCR Pharmaceuticals Co., Ltd.

About Lysosomal Storage Disorders
Lysosomal storage disorders are genetic diseases in which certain enzymes or proteins that remove unwanted substances from cells do not work as they should. When that happens, those substances build up inside the lysosomes and damage cells and tissues. The Symptoms differ depending on what builds up, and many of these conditions also affect the central nervous system.

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

– Research Describes the Potential of JCR’s Platform Technologies, Including JUST-AAV Gene Therapy, to Facilitate Delivery of Therapies to the Central Nervous System –

Hyogo, Japan – May 18, 2026 – JCR Pharmaceuticals Co., Ltd. (TSE 4552; “JCR”), a global specialty biopharmaceutical company dedicated to developing therapies for rare and genetic diseases, announced today that it presented preclinical data from its novel platform technologies, including JUST-AAV gene therapy, in oral and poster sessions at the American Society of Gene and Cell Therapy (ASGCT) 29th Annual Meeting, being held May 11-15, 2026, in Boston, Massachusetts. Additionally, Alexion, AstraZeneca Rare Disease, presented preclinical data from a research collaboration that applies JCR’s JUST-AAV technology in an oral session.

JUST-AAV is JCR’s novel adeno-associated vector (AAV) vector platform technology, which is under preclinical investigation, and is designed to enhance targeted delivery to the central nervous system (CNS) and/or muscle and reduce liver tropism, aiming to improve safety and efficacy of AAV-based gene delivery technologies. JUST-AAV encompasses a range of vector types optimized for various target tissues, including liver-sparing, muscle-targeting, and brain-targeting variants. This proprietary technology holds promise for advancing the field of AAV-based gene therapy.

“The presented preclinical results demonstrate that JCR’s novel capsid platform is able to deliver therapeutic agents to the central nervous system more efficiently than conventional AAV9, while reducing liver accumulation,” said Hiroyuki Sonoda, Ph.D., President and Chief Scientific Officer at JCR Pharmaceuticals. “These data represent an advancement toward potential new treatment options for previously challenging CNS diseases. This research is an important step forward in our ongoing commitment to developing innovative solutions for complex healthcare challenges, including neurodegenerative disorders.”

Development of an AAV-Based Gene Therapy for GM1 Gangliosidosis Using a  Transferrin Receptor Antibody–Fused Enzyme with Markedly Enhanced Therapeutic  Efficacy (Presentation Number: 391)

Presenter: Saki Matsushima, Ph.D. (The Jikei University School of Medicine, Division of Gene Therapy, Research Center for Medical Sciences, Tokyo, Japan)

Researchers reported on preclinical data from an AAV9 gene therapy encoding a transferrin receptor (TfR)-targeted, blood-brain barrier (BBB)-penetrable lysosomal enzyme, which is being investigated for GM1 gangliosidosis. Researchers used a plasmid encoding β-galactosidase fused to an antibody-derived TfR-binding domain to enable receptor-mediated BBB transport once the transgene is expressed in the treated animals. They demonstrated proof-of-concept in a mouse model of GM1 gangliosidosis using a mouse TfR-targeting construct.

Intravenous administration of the liver-specific AAV vector resulted in robust hepatic expression and high circulating levels of the TfR-targeted β-galactosidase, enabling efficient distribution to peripheral tissues and the CNS. In the animals, the mouse TfR-targeting construct markedly reduced GM1 ganglioside accumulation in the brain, improved neurological function, and significantly extended survival. Additionally, in GM1 mice expressing human TfR, the human TfR-targeted enzyme demonstrated comparable biodistribution, CNS penetration, and therapeutic efficacy. Researchers did not observe any apparent toxicity associated with hepatic expression or systemic enzyme exposure.

These results demonstrate that AAV gene therapy expressing a TfR-targeted, BBB-penetrable lysosomal enzyme enables robust CNS correction in GM1 gangliosidosis. The successful evaluation of a human TfR-targeted construct in a humanized disease model, leveraging a clinically validated BBB transport strategy, provides strong translational support for first-in-human clinical trials.

Long-Term Efficacy and Neuroprotection by Systemically Administered, CNS-Targeting  AAV Capsids in Mouse Models of Neuronal Ceroid Lipofuscinosis (CLN1 and CLN2)  (Poster Number: 3460)

Lead Author: Tomoki Hirashima (JCR Pharmaceuticals)

JCR researchers reported on the long-term efficacy of JUST-AAV-mediated gene therapy based on preclinical data from mouse models of neuronal ceroid lipofuscinosis (CLN1 and CLN2) compared with recombinant enzyme replacement therapy and conventional AAV approaches. In the CLN1 (PPT1 deficiency) study, researchers assessed five groups across survival, motor function, cognition, neuropathology, and retinal integrity. Mice in the disease control and recombinant PPT1 group showed no survival benefit, with death occurring between weeks 31–41. Mice treated with conventional AAV9-PPT1 extended survival to weeks 53–65. In contrast, mice treated with JCR’s investigational therapy, JUST-AAV-PPT1, had an almost comparable life span to healthy control animals. The proportion of SCMAS-, CD68-, and GFAP-positive areas—markers of lysosomal storage and inflammation—were markedly reduced in the JUST-AAV-PPT1 group, indicating suppressed neuroinflammation and microglial activation. Brain extracts confirmed elevated PPT1 enzymatic activity in JUST-AAV–treated mice. Researchers noted that preservation of locomotor function at 54 weeks of age was indistinguishable from healthy wildtype animals. Measurement of the retinal ganglion cell layer thickness revealed a significant loss in thickness in diseased animals, while retinal thickness was preserved in the JUST-AAV-PPT1–treated mice.

In the CLN2 (TPP1 deficiency) study, systemic administration of JCR’s investigational therapy, JUST-AAV-TPP1, led to a comparably pronounced therapeutic effect regarding survival compared with healthy control mice. Post-mortem analyses confirmed elevated TPP1 activity in brain tissue, supporting robust CNS delivery and sustained therapeutic benefit. Researchers concluded that JUST-AAV–mediated gene therapy significantly extended lifespan and improved pathogenic phenotypic changes in CLN1 and CLN2 mouse models, indicating the ability to efficiently deliver the transgene to the CNS upon systemic administration. Based on these preclinical results, the JUST-AAV technology holds strong potential as a next-generation gene therapy platform for lysosomal storage disorders and other neurodegenerative diseases.

Alexion, AstraZeneca Rare Disease presented the following:

AAV Capsid Presenting a Miniaturized Anti–Transferrin Receptor Antibody Enables Broad  CNS, Liver-detargeted Biodistribution (Presentation Number: 427)

Researchers reported on preclinical data that evaluated a TfR-targeted JUST-AAV capsid, based on the JUST-AAV technology, that expresses a miniaturized anti–TfR receptor binder on the surface of the capsid and incorporates sequence modifications to minimize liver exposure. Following a single intravenous dose in mouse models and non-human primates, the capsid enabled broad CNS biodistribution, while increasing brain-to-liver exposure ratios relative to AAV9. Analyses demonstrated dose-dependent transgene expression with favorable tolerability. Researchers concluded that these data support a translational platform for broad brain distribution with reduced liver exposure.

The data referenced are from preclinical studies. Study limitations were not discussed.

About the American Society of Gene and Cell Therapy (ASGCT)
The American Society of Gene and Cell Therapy (ASGCT) is the primary professional membership organization for gene and cell therapy. The Society’s members are scientists, physicians, patient advocates, and other professionals. The mission of the ASGCT is to advance knowledge, awareness, and education, leading to the discovery and clinical application of genetic and cellular therapies to alleviate human disease. For more information, please visit www.asgct.org.

About the JUST-AAV Platform Technology
JUST-AAV is a proprietary platform technology that utilizes modified adeno-associated virus (AAV) vectors. The technology entails insertion of miniaturized antibodies against receptors on selected tissues, organs or the blood-brain barrier onto the capsid surface, enhancing targeted delivery to those tissues and organs. Further capsid modifications minimize liver tropism and potentially mitigate hepatoxicity, which is a commonly observed safety concern. The name is derived from “JCR” “Ultimate destination of organ” “Safeguarding against off-target delivery” and “Transformative technology” reflecting its potential for broad application across various diseases.

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