Therapy Areas: Central Nervous System
Takeda to Commercialize Next-Generation Hunter Syndrome Therapy Through Collaboration with JCR Pharmaceuticals
1 October 2021 - - Japan-based pharmaceutical companies Takeda Pharmaceutical company Ltd. (TSX: 4502) (NYSE: TAK) and JCR Pharmaceuticals Co., Ltd. (TSX: 4552) have forged a geographically-focused exclusive collaboration and license agreement to commercialize JR-141 (INN: pabinafusp alfa), an investigational, next-generation recombinant fusion protein of an antibody against the human transferrin receptor and iduronate-2-sulfatase enzyme for the treatment of Hunter syndrome, the companies said.

Hunter syndrome is caused by a deficiency of IDS and manifests in different forms. JR-141, applied with J-Brain Cargo, JCR's proprietary blood-brain barrier technology, is engineered to transport the therapeutic enzyme across the BBB to directly reach the brain and address both the somatic and neuronopathic manifestations of the disease, which can lead to progressive cognitive decline.

Under the terms of the exclusive collaboration and license agreement, Takeda will exclusively commercialize JR-141 outside of the United States, including Canada, Europe, and other regions (excluding Japan and certain other Asia-Pacific countries).

JCR will receive an upfront payment for such ex-US license, and is eligible to receive additional development and commercial milestones as well as tiered royalties on potential sales.

The two companies will collaborate to bring this therapy to patients as quickly as possible upon completion of the global Phase 3 program, which will be conducted by JCR.

Takeda receives an option under a separate option agreement, which allows Takeda to acquire an exclusive license to commercialize JR-141 in the US upon completion of the Phase 3 program.

JR-141 met its primary endpoint in an open-label Phase 2/3 clinical trial in Japan demonstrating significant reductions in heparan sulfate in the cerebrospinal fluid, a biomarker for assessing the drug's effectiveness in reducing disease-causing substrate in the central nervous system, in all subjects for whom measurements were available after 52 weeks of treatment.

Somatic disease control was maintained in patients who switched from standard enzyme replacement therapy.

The study also demonstrated an improvement in somatic symptoms in participants who had not previously received standard ERT prior to the start of the trial.

Additionally, a neurocognitive development assessment demonstrated maintenance or improvement of age-equivalent function in 21 of the 25 patients at one year.

There were no reports of serious treatment-related adverse events in the trial.

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 is expected to be effective against the neuronopathic manifestations of the disease by crossing the BBB through transferrin receptor mediated transcytosis using J-Brain Cargo, JCR's proprietary BBB technology. Uptake into cells is mediated through the transferrin receptor and mannose-6-phosphate receptor.

JCR has advanced development activities by establishing the necessary evidence from the molecular design stage to the nonclinical and clinical trial phases.

In non-clinical trials, JCR has confirmed both high affinity binding of JR-141 to transferrin receptors, and passage across the BBB into neuronal cells as evidenced by electron microscopy.

In addition, JCR has confirmed that using J-Brain Cargo technology, enzymes are taken up into various brain tissues. A decrease in substrate accumulation has also been confirmed in an animal model of Hunter syndrome.

In several clinical trials with JR-141, JCR obtained evidence of reduction of heparan sulfate concentrations in the CSF, a biomarker for assessing the drug's effectiveness in reducing disease-causing substrate in the central nervous system, consistent with the results obtained from non-clinical studies.

JCR also obtained clinical results that demonstrate positive effects of JR-141 on neurocognition.

JR-141 was approved by the Ministry of Health, Labour and Welfare and marketed since May 2021 under the brand name "IZCARGO I.V. Infusion 10mg."
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