On September 30, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") and JCR Pharmaceuticals Co., Ltd. (TSE:4552) ("JCR") reported 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 (IDS) enzyme for the treatment of Hunter syndrome (also known as Mucopolysaccharidosis type II or MPS II) (Press release, Takeda, SEP 30, 2021, View Source [SID1234590585]). 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 (BBB) 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.

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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-U.S. 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 U.S. upon completion of the Phase 3 program.

"Takeda is committed to continuously improving the way Hunter syndrome is treated. JR-141 introduces a new way to deliver proteins across the blood-brain barrier, overcoming our current challenges to treat the underlying neuronopathic manifestations of Hunter syndrome and help maintain or improve cognitive function in these patients," said Dan Curran, M.D., Head, Rare Genetics & Hematology Therapeutic Area Unit at Takeda. "We will work closely with JCR to apply our expertise in enzyme replacement therapies with the hope of bringing this potentially transformative therapy to patients as quickly as possible."

"JCR is pleased to have reached an agreement with Takeda who is well placed to achieve our common goal of maximizing the impact of JR-141," said Shin Ashida, President, Chairman of JCR. "Our mission is to provide transformative treatment options as soon as possible to patients with lysosomal storage disorders (LSDs) with central nervous system symptoms, such as Hunter syndrome. JR-141 is the first-ever approved biopharmaceutical in Japan that penetrates the blood-brain barrier. I expect that we will be able to achieve this mission through our partnership with Takeda to deliver a new treatment option to Hunter patients around the world as swiftly as possible."

JR-141 met its primary endpoint in an open-label Phase 2/3 clinical trial in Japan demonstrating significant reductions in heparan sulfate (HS) 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 (ERT). 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.1

About JR-141

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.2,3,4 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.5,6,7,8

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."

About Hunter Syndrome

Hunter syndrome is a severely debilitating, rare lysosomal disease caused by a deficiency of iduronate-2-sulfatase, an enzyme that is needed to break down substances in the body called glycosaminoglycans (GAGs).9 Without this enzyme, GAGs can build up, causing a range of disease-related signs and symptoms.9,10 Roughly two of every three patients with Hunter syndrome are also affected with progressive cognitive decline.11 Hunter syndrome affects 1 in 162,000 total live births, and almost exclusively males.12

On September 30, 2021 Merck, a leading science and technology company, reported a mutual decision with GSK to terminate their agreement on bintrafusp alfa, effective September 30, 2021 (Press release, Merck & Co, SEP 30, 2021, View Source [SID1234590583]).

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The decision is based on the clinical trial data generated to date, most notably the previously reported results from the INTR@PID Lung 037 study, which did not replicate the encouraging data observed in earlier studies. Based on the data generated during the agreement, no milestone payments were made by GSK and no future milestone obligations remain.

The INTR@PID clinical program sought to validate the potential of the novel mechanism of simultaneously blocking TGF-ß and PD-L1, with the ambition to improve outcomes for patients with difficult-to-treat cancers. Given the extent of the clinical program, Merck will deepen its scientific leadership in the field and interrogate the data leveraging the power of advanced analytics. The important insights this program has yielded about the biology of TGF-β will inform the collective understanding of this pathway.

Merck is a science-led organization dedicated to delivering transformative medicines with the goal of making a meaningful difference in the lives of people affected by cancer. Our oncology research efforts, comprised of 10 ongoing development programs, aim to leverage our synergistic portfolio in oncogenic pathways, immuno-oncology, and DNA Damage Response (DDR) to tackle challenging tumor types in gastrointestinal, genitourinary, and head and neck and thoracic cancers. Learn more at View Source

All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

On September 30, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that Manuel Litchman, M.D., President and Chief Executive Officer, and members of the Mustang Leadership Team will participate in a fireside chat at Chardan’s Virtual 5th Annual Genetic Medicines Conference, taking place on Tuesday, October 5, 2021, at 8:00 a.m. ET (Press release, Mustang Bio, SEP 30, 2021, View Source [SID1234590581]). The company will also participate in one-on-one meetings during the conference. A live webcast of the company’s chat will be available on the Events page of the Investor Relations section of Mustang’s website, www.mustangbio.com, for approximately 30 days after the meeting.

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On September 30, 2021 Reata Pharmaceuticals, Inc. (Nasdaq: RETA) ("Reata," the "Company," or "we"), a clinical-stage biopharmaceutical company, reported that it has completed its pre-New Drug Application ("NDA") meeting with the United States Food and Drug Administration ("FDA") for omaveloxolone for the treatment of patients with Friedreich’s ataxia and reaffirmed its plan to submit an NDA in the first quarter of 2022 (Press release, Reata Pharmaceuticals, SEP 30, 2021, View Source [SID1234590580]).

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The purpose of the pre-NDA meeting was to discuss the content of Reata’s planned NDA submission. We plan to submit the NDA seeking standard approval for omaveloxolone for the treatment of Friedrich’s ataxia. We are not planning to conduct a second pre-approval clinical study prior to the submission. The FDA indicated that the appropriate approval pathway would be a matter of review after submission of the NDA. In response to our questions about the contents of the filing and because of the seriousness of the indication, the FDA exercised its discretion subject to review to permit us to submit the results of certain nonclinical and clinical studies after approval.

"We are pleased with the outcome of our recent pre-NDA meeting and that we have a path to submit our NDA in the first quarter of 2022," said Warren Huff, Reata’s President and Chief Executive Officer. "Friedreich’s ataxia is a severe, ultra-rare disease that affects approximately 5,000 patients in the United States. We remain committed to our goal of working with the FDA to secure regulatory approval for omaveloxolone as quickly as possible for patients with this devastating disease."

"Omaveloxolone could be the first drug approved for the treatment of Friedreich’s ataxia—actually the first drug approved for any ataxia," said Dr. Susan Perlman, MD, Professor, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA. "The MOXIe Part 2 study with omaveloxolone is the first to demonstrate a significant improvement in neurological function in patients with Friedreich’s ataxia. While not a cure, if approved, Friedreich’s ataxia would finally become a treatable disease, something the Friedreich’s ataxia community has been working towards for a long time."

About Friedreich’s Ataxia

Friedreich’s ataxia is a rare, inherited, life-shortening, debilitating, and degenerative neuromuscular disorder, which is normally diagnosed during adolescence. Friedreich’s ataxia is caused by a trinucleotide repeat expansion in the first intron of the frataxin gene, which encodes the mitochondrial protein frataxin. Pathogenic repeat expansions can lead to impaired transcription and reduced frataxin expression, which can result in mitochondrial iron overload and poor cellular iron regulation, increased sensitivity to oxidative stress, and impaired mitochondrial ATP production. Patients with Friedreich’s ataxia experience symptoms in childhood, including progressive loss of coordination, muscle weakness, and fatigue that commonly resulting in motor incapacitation with patients requiring a wheelchair by their teens or early 20s. Patients with Friedreich’s ataxia may also experience visual impairment, hearing loss, diabetes, and cardiomyopathy. Based on literature and proprietary research, we believe Friedreich’s ataxia affects approximately 5,000 children and adults in the United States and 22,000 individuals globally. There are currently no approved therapies for the treatment of patients with Friedreich’s ataxia.

About Omaveloxolone

Omaveloxolone is an investigational, oral, once-daily activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling. The FDA has granted Orphan Drug designation to omaveloxolone for the treatment of Friedreich’s ataxia. The European Commission has granted Orphan Drug designation in Europe to omaveloxolone for the treatment of Friedreich’s ataxia.

On September 30, 2021 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), a company developing new drugs for the treatment of cancer and fibrosis, reported that publication of a key paper from the Garvan Institute of Medical Research ("Garvan") (Press release, Amplia Therapeutics, SEP 30, 2021, View Source;[email protected] [SID1234590579]). The paper, which describes the fundamental biology underpinning Amplia’s planned Phase 2 clinical trial in pancreatic cancer patients, further highlightsthe potential benefits of using a focal adhesion kinase (FAK) inhibitor prior to administration of standard chemotherapy.

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Entitled "Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status" the paper has been published in the high impact peer-reviewed journal Science Advances. 1 Professor Paul Timpson, a leading researcher in FAK biology at Garvan and a member of Amplia’s Scientific Advisory Board, led the research program which has shown that in mice that have been implanted with human pancreatic cancer tissue, pre-treatment with a FAK inhibitor (‘priming’) increased the responsiveness of the cancer to subsequently administered gemcitabine/Abraxane chemotherapy. Furthermore, FAK-priming reduced the metastatic spread of tumour cells to secondary sites such as the liver.

"There have been several publications over the last two years that have highlighted the potential of FAK inhibitors in pancreatic cancer, including their ability to work synergistically with chemotherapy agents" said John Lambert, CEO of Amplia: "This latest study from our collaborators at the Garvan Institute is particularly exciting as its replicates the approach that we are taking to treat first line pancreatic cancer patients in our recently announced Phase 2 clinical trial. We believe that making an established standard of care, namely chemotherapy with gemcitabine/Abraxane, more effective offers a very promising approach for improving the outcomes for these patients".