Oncogenic Osteomalacia

Recently, Kyowa Kirin Co., Ltd., a Japanese pharmaceutical company, announced that it has signed a promotion and distribution agreement with NewBridge Pharmaceuticals for two drugs, aiming to cover the Middle East and North Africa (MENA) regions within its existing portfolio of rare disease products. According to the terms of the agreement, NewBridge will have exclusive distribution rights in Algeria, Iraq, Libya, and Jordan for CRYSVITA® (burosumab) for the treatment of X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), as well as POTELIGEO® (mogamulizumab monoclonal antibody) for the treatment of two types of cutaneous T-cell lymphoma, including a rare form of non-Hodgkin lymphoma. Mogamulizumab (Poteligeo) is a humanized, defucosylated, IgG1 monoclonal antibody specifically targeting CCR4. By binding to the N-terminal domain of CCR4, mogamulizumab induces antibody-dependent cellular cytotoxicity. Burosumab is a monoclonal antibody specifically engineered to bind and neutralize the human protein fibroblast growth factor 23 (FGF23). In patients with X-linked hypophosphatemia (XLH), excessive FGF23 leads to low levels of phosphate in the blood, which adversely affects bone health. By inhibiting the action of FGF23, burosumab can increase phosphate levels in the blood, promote bone mineralization, and improve bone density and structure. Regarding the CCR4 antibody: Mogamulizumab Mogamulizumab was first approved in Japan in 2012 for the treatment of relapsed or refractory CCR4-positive adult T-cell leukemia/lymphoma (ATCL) and in 2014 for relapsed or refractory CCR4-positive cutaneous T-cell lymphoma (CTCL). CCR4 is a member of the chemokine receptor subfamily within the GPCRs (G-protein coupled receptors) family. By binding to the N-terminal domain of CCR4, mogamulizumab induces antibody-dependent cellular cytotoxicity (ADCC). The lack of fucosylation enhances the ADCC of mogamulizumab against CCR4-positive cells, offering a mechanistic advantage over traditionally glycosylated monoclonal antibodies. In August and November of 2018, the FDA and EMA respectively approved Mogamulizumab for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. Mogamulizumab: New Clinical Indications Beyond the classical targeting of CCR4 for inflammatory diseases and cancer therapy, researchers at Kyowa Kirin are exploring the use of mogamulizumab in the study of chronic neurodegenerative diseases. Human T-cell leukemia virus type 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. HAM/TSP was first described in the 19th century in Jamaica, but it wasn't until the 1980s that the cause of the disease was identified as the HTLV-1 retrovirus infection. HAM/TSP leads to chronic disability and thus imposes a significant public health burden in areas where HTLV-1 infection is endemic. Due to the lack of accurate animal models, research progress has been limited. Additionally, the treatment for HAM/TSP remains highly unsatisfactory: Antiretroviral drugs have minimal impact on the infection, and although potential disease-modifying therapies are widely used, their effectiveness has not yet been confirmed. Previous studies have shown that in both patients with HAM/TSP and HTLV-1 carriers, there is a high rate of HTLV-1 infection in CCR4 positive T cells. Therefore, researchers initiated a Phase I/IIa clinical trial for this indication, along with a study on the long-term safety and efficacy of this monoclonal antibody. The results showed that the monoclonal antibody mogamulizumab reduced the viral load of the original virus in peripheral blood in a dose-dependent manner, decreased levels of the inflammatory marker CXCL10 (C-X-C motif chemokine ligand 10) and methotrexate in cerebrospinal fluid (CSF), and improved clinical symptoms such as spasticity and movement disorders. These findings were published in the New England Journal of Medicine in 2018. In updated clinical study results from 2024, at the end of the double-blind period, the mogamulizumab monoclonal antibody group showed a significant reduction in HTLV-1 original viral load (-59.39±29.91% vs. placebo group 2.32±36.31%) and a significant decrease in levels of methotrexate (p < 0.001) and CXCL10 (p = 0.004) in CSF. Although no significant differences were observed in clinical benefits (the primary endpoint was the proportion of patients with an improvement of ≥1 grade in the Osame Motor Disability Score (OMDS)), mogamulizumab monoclonal antibody may provide long-term clinical benefits by preventing disease progression. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

GALASHIELS, Scotland & MARLOW, England--( BUSINESS WIRE )--Kyowa Kirin International (KKI), a wholly owned subsidiary of Kyowa Kirin Co., Ltd. (TSE:4151, Kyowa Kirin) and a Japan-based global specialty pharmaceutical company, announced today the signing of a Promotion and Distribution Agreement with NewBridge Pharmaceuticals for the distribution of its existing rare disease portfolio across the Middle East and North Africa (MENA). Under the terms of the agreement, NewBridge will commercialise CRYSVITA ® (burosumab) for the treatment of X-Linked Hypophosphataemia (XLH) and Tumour-Induced Osteomalacia (TIO), as well as POTELIGEO ® (mogamulizumab) for two subtypes of cutaneous T-cell lymphoma (CTCL), a rare non-Hodgkin’s lymphoma. As part of the agreement, NewBridge will exclusively distribute the two products across MENA countries of Algeria, Iraq, Libya and Jordan. KKI and NewBridge also hope to collaboratively address a number of challenges facing the rare disease community in the region by supporting disease awareness, improving time to diagnosis, and improving access to innovative treatments indicated for rare and orphan diseases. Jeremy Morgan, President of KKI, commented: “At Kyowa Kirin our purpose is to deliver life-changing medicines and make people smile. We are pleased to be entering into this agreement with NewBridge Pharmaceuticals who have a clear mission to transform the lives of MENA patients and their families. With a commitment to delivering life changing value for people impacted by under-diagnosed and under-served diseases, this agreement is key to ensuring patients living with XLH, TIO and CTCL are able to access the medicines they need, and is another positive step on our journey.” "Given the high prevalence of rare diseases in the MENA region, I am personally inspired and proud that we at NewBridge are building on our existing partnership with Kyowa Kirin with the addition of their rare disease products to our region,” added Joe Henein, President & CEO of NewBridge Pharmaceuticals. “This collaboration totally aligns with our mission to provide access to new therapies for patients, aiming to alleviate their suffering and enhancing their quality of life." About CRYSVITA (burosumab) CRYSVITA (burosumab) is a recombinant human monoclonal antibody (mAb) that binds to the protein fibroblast growth factor 23 (FGF23). This has the impact of inhibiting the action of FGF23, allowing phosphate regulation in the body to be restored. 1 About POTELIGEO (mogamulizumab) Mogamulizumab is a first-in-class humanised mAb directed against CC chemokine receptor 4 (CCR4), a protein consistently expressed in both mycosis fungoides and Sézary syndrome 2–4 once mogamulizumab binds to CCR4, it increases attraction of immune cells from the immune system to destroy the cancerous cells. 5 About Kyowa Kirin Kyowa Kirin aims to discover novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients affected by severe and rare diseases. A shared commitment to our values, to sustainable growth, and to making people smile unites us across our four regions—Japan, Asia Pacific, North America, and EMEA/International. You can learn more about the business of Kyowa Kirin at: https://www.kyowakirin.com About NewBridge Pharmaceuticals NewBridge Pharmaceuticals is a regional specialty company with a comprehensive pharmaceutical platform of services and expertise, established to bridge the access gap and partner with global pharma and biotech companies to in-license and commercialise innovative therapeutics that address unmet medical needs into the Middle East and North Africa (MENA) regions. For more information, please visit www.nbpharma.com References 1 Electronic Medicines Compendium. Crysvita 10 mg solution for injection. Available from: https://www.medicines.org.uk/emc/product/9779/smpc#gref . Last accessed: November 2023. 2 Ferenczi K, et al. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119:1405–10. 3 Yoshie O, et al. Frequent Expression of CCR4 in Adult T-Cell Leukemia and Human T-cell Leukemia Virus Type 1-transformed T cells. Blood. 2002;99(5):1505–11. 4 Ishida T, et al. Clinical Significance of CCR4 Expression in Adult T-cell Leukemia/Lymphoma: Its Close Association With Skin Involvement and Unfavorable Outcome. Clin Cancer Res. 2003;9:3625–34. 5 Duvic M, et al. Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential. Ther Adv Hematol. 2016;7(3):171–174. KKI/INT/KKI/0959 Date of preparation: July 2024

Kyowa Kirin is retooling its global operations, including divesting its China business and cutting back on small-molecule drug discovery research. Abdul Mullick, the company's chief international business officer, cited "increasing challenges in the APAC (Asia-Pacific) region" as a driving factor behind the decisions.In a deal valued at CNY 750 million ($105 million), Kyowa will transfer its Chinese operations, including five established brands, to Hong Kong-based WinHealth Pharma. WinHealth will also obtain commercial rights to Kyowa's Crysvita (burosumab) and Poteligeo (mogamulizumab) in China. The former is an antibody approved as a treatment for X-linked hypophosphataemia and tumour-induced osteomalacia, while the latter is approved for two types of cutaneous T-cell lymphoma.Kyowa also struck agreements with DKSH Holding for commercial rights to seven established brands across various APAC markets, as well as rights to Crysvita and Poteligeo in specific countries.Meanwhile, Kyowa is implementing a "significant reduction" in its in-house small-molecule drug discovery research work. According to the company, the move reflects its pivot towards antibody technologies and haematopoietic stem cell gene therapy, with a sharpener focus on areas such as bone and mineral disorders, haematologic cancers, intractable haematologic diseases, and rare diseases.The restructuring extends beyond research, affecting manufacturing operations as well. Specifically, Kyowa plans to reduce its workforce in chemistry, manufacturing and controls (CMC) research and quality divisions. To facilitate this transition, the company is offering a voluntary early retirement programme to eligible employees in Japan.