Oncogenic Osteomalacia

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.

Ultragenyx and Mereo BioPharma unveiled longer-term results for their investigational anti-sclerostin antibody setrusumab showing sustained reductions in fracture rates and improvements in bone mineral density (BMD) for patients with the rare, inherited brittle bone disease osteogenesis imperfecta (OI).Previously reported six-month data had shown a 67% reduction in annualised rate of radiologically confirmed fractures across all 24 patients in the Phase II portion of the pivotal ORBIT trial following at least six months of treatment with setrusumab.The latest results indicate this benefit was maintained in OI patients with at least 14 months of follow-up. Setrusumab also resulted in a mean 22% increase in lumbar spine BMD at 12 months compared to baseline levels across all age groups in the study, which includes patients from 5 to <26 years old. The companies said this effect translated to a substantial normalisation in Z-score of +1.25, progressing from the +0.85 increase seen at 6 months."The clinically meaningful continued improvement in BMD suggests that new and stronger bone is being created that has resulted in an important reduction in fractures across age groups and types of OI," noted Eric Crombez, chief medical officer at Ultragenyx.No new safety signals emerged with the longer-term setrusumab exposure. There were no treatment-related serious adverse events (AEs) either, and AEs were "generally consistent" with those seen previously in the Phase IIb ASTEROID study of setrusumab in 112 adults with OI, the companies said. Detailed 14-month data will be presented at a future scientific meeting.Late-stage testing under wayThe Phase III portion of the ORBIT study has enrolled an additional 158 patients aged 5 to 25 years, randomised to receive setrusumab or placebo, with a primary endpoint of annualised clinical fracture rate. Primary completion is set for early next year. Meanwhile, in the open-label Phase III COSMIC study, 69 children ages 2 through 7 years were randomised to setrusumab or intravenous bisphosphonate therapy, assessing reduction in total fracture rate.Enthusiasm appears to be building for setrusumab. In a recent note, Goldman Sachs analyst Salveen Richter expressed confidence in the drug based on positive feedback from key opinion leaders regarding the Phase II data. She noted "the potential for setrusumab to improve bone formation and strength in addition to reducing fractures via its sclerostin inhibition mechanism, a key differentiator vs. standard-of-care bisphosphonates."Ultragenyx entered a collaboration and licence agreement with Mereo in 2020 to bolster its existing bone franchise, which includes Crysvita (burosumab-twza) for X-linked hypophosphatemia and tumour-induced osteomalacia. Mereo received $50 million upfront as part of the deal and is eligible for milestones up to $254 million.