NEWS RELEASE
June 21, 2023

Submission of New Drug Application for NS-87 (daunorubicin and cytarabineliposome injection) in Japan

Kyoto, Japan, June 21, 2023 - Nippon Shinyaku Co., Ltd. (Nippon Shinyaku; Headquarters,Kyoto; President, Toru Nakai) announced today that it submitted a New Drug Application(NDA) to the Ministry of Health, Labour & Welfare (MHLW) for the marketing approval of NS87 (daunorubicin and cytarabine liposome injection) for the treatment of high-risk acute
myeloid leukemia (AML)* in Japan. Nippon Shinyaku acquired a license for NS-87 from Jazz
Pharmaceuticals plc (Headquarters: Dublin, Ireland, Chairman and CEO: Bruce C. Cozadd)
on March 30, 2017.
AML is a disease of clonal proliferation of immature myeloid cells, and results from genetic
abnormalities in myeloblasts which are immature blood cells. The uncontrollable growth ofleukemia cells in the bone marrow prevents the production of normal blood which results invarious symptoms such as infections and bleeding.1 Although multiple AML drugs have beenlaunched in recent years and the outcomes for some patient groups have improved, many
patients still do not have long-term survival. Novel therapeutic agents with greater efficacy
are needed.2NS-87 is approved in the U.S. (under the name of Vyxeos® **) by the U.S. Food and Drug
Administration (FDA) for the treatment of newly-diagnosed high-risk AML in adult andpediatric patients one year and older.3 It is also approved as Vyxeos® Liposomal by theEuropean Medicines Agency (EMA) for the treatment of adults with newly-diagnosed highrisk AML.4 NS-87 is an investigational treatment with a dual-drug liposomal formulation thatdelivers a fixed synergistic ratio of daunorubicin and cytarabine.4
In a Phase III study of adult patients, aged 60-75, with newly diagnosed high-risk AML, NS87 demonstrated a statistically significant improvement in overall survival compared to thecurrent conventional treatment group of 7+3 cytarabine and daunorubicin chemotherapy.5
Data from a prospectively planned final five-year analysis of this study confirmed that thisimproved overall survival, following treatment with NS-87, was maintained.61/3

The filing is based on data from the Phase III trial conducted by Jazz Pharmaceuticals and aPhase I/II trial conducted by Nippon Shinyaku in patients with high-risk AML. NS-87 wasdesignated as an orphan drug by MHLW for the indication of AML in May 2022.
We are working with the MHLW to bring NS-87 as a new therapeutic option to people livingwith high-risk AML in Japan as soon as possible.
* High-risk acute myeloid leukemia: We define as therapy-related acute myeloid leukemia (tAML) or AML with myelodysplasia-related changes (AML-MRC)** A brand belonging to Jazz Pharmaceuticals
About NS-87 (daunorubicin and cytarabine liposome injection)
NS-87 is a liposomal formulation of a fixed combination of cytarabine and daunorubicin at asynergistic 5:1 molar ratio. The 5:1 molar ratio has been shown to maximise synergistic
antitumor activity in AML. After the drug is taken up into leukemic cells in the bone-marrow,cytarabine and daunorubicin will be released to exert their antitumor effects.
References
1. Japanese Society of Hematology. Practical Guidelines for Hematological Malignancies,
2018 (revised version), Kanehara & Co., Ltd. (Japanese only).
2. Gurnari C et al. Deciphering the Therapeutic Resistance in Acute Myeloid Leukemia. IntJ Mol Sci. 2020; 21(22):8505.
3. U.S. Food and Drug Administration. Vyxeos Prescribing Information. Published 2017.
Updated March 2021. Accessed May, 2023. Further information on FDA guidance canbe found at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209401s006lbl.pdf.
4. European Medicines Agency. Vyxeos Summary of Product Characteristics. Published

August 2018. Accessed May, 20232. Further information on EMA guidance can be foundat:

https://www.ema.europa.eu/en/documents/product-information/vyxeos-liposomal-epar-product-information_en.pdf

5. Lancet JE et al. CPX-351 (cytarabine and daunorubicin) Liposome for Injection versus
Conventional Cytarabine Plus Daunorubicin in Older Patients with Newly Diagnosed
Secondary Acute Myeloid Leukemia. J Clin Oncol. 2018; 36(26):2684-2692.
6. Lancet JE et al. CPX-351 versus 7+3 Cytarabine and Daunorubicin Chemotherapy inOlder Adults with Newly Diagnosed High-Risk or Secondary Acute Myeloid Leukaemia:
5-Year Results of a Randomised, Open-Label, Multicentre, Phase 3 Trial. The Lancet.
Vol. 2021; 8(7):e481-e491.
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ContactCorporate Communications Dept., Nippon Shinyaku Co., Ltd.
FAX: +81-75-321-9128

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