Announcement of in-licensing of technology related to a small molecule tyrosine kinase inhibitor fostamatinib

Kissei Pharmaceutical Co., Ltd. (Chairman and CEO: Mutsuo Kanzawa, "Kissei") today announced that it has signed a contract with Rigel Pharmaceuticals, Inc. (Headquarter: USA, President and CEO, Raul Rodriguez, hereinafter referred to as "Rigel") for the exclusive development and marketing rights of a small molecule tyrosine kinase inhibitor fostamatinib (non-proprietary name) (hereinafter referred to as "fostamatinib").

Under this contract, Kissei acquires the exclusive development and marketing rights of fostamatinib in Japan, China, Korea, and Taiwan.

Fostamatinib is an orally available small molecule compound that was discovered by Rigel. By inhibiting SYK,^*1 which is a tyrosine kinase, fostamatinib suppresses phagocytosis and destruction of platelets by macrophages. "Idiopathic thrombocytopenic purpura (ITP)"^*2, one of the planned indications of fostamatinib, decreases the platelet count despite the absence of other obvious diseases or the use of drugs that cause thrombocytopenia, subsequently leading to bleeding. The disease is designated as "designated intractable disease" by the Minister of Health, Labour and Welfare. Fostamatinib is designated as an orphan drug for the indication of chronic ITP in the USA and has been marketed by Rigel since May 2018 in the USA. Its application for marketing authorization was validated by the European Medicines Agency (EMA) in Europe in October and is currently under review. Fostamatinib is in clinical development for the indications of "autoimmune hemolytic anemia (AIHA)"^*3 and "IgA nephropathy"^*4 in the US and other countries.

Kissei has been working to expand the product portfolio in the areas of urology, kidney and dialysis, and high unmet medical needs. By concluding this contract, we will further strengthen our efforts to treat rare diseases and to provide fostamatinib treatment earlier to patients with intractable diseases.

The impact of this contract on the consolidated business forecasts for the fiscal year ended in March 2019 is currently under review. We will promptly disclose it at the time of the announcement of the financial results of the second quarter of the fiscal year ended in March 2019, scheduled on November 6, 2018.


《Reference》
*1: SYK (Spleen Associated Tyrosine Kinase)

SYK is a tyrosine kinase, an enzyme that specifically phosphorylates tyrosine residues in proteins. It is involved in histamine release and cytokine production by mast cells via activation of IgE receptor, phagocytosis/destruction of autoantibody (IgG)-bound platelets by macrophages, activation of osteoclasts, and differentiation as well as activation of B lymphocytes. It is also known to be related to certain types of cancer, autoimmune diseases, and fungal and viral infections.

*2: Idiopathic thrombocytopenic purpura (ITP)

ITP is an autoimmune disease in which autoantibodies against platelet membrane proteins are produced. These antibodies bind to platelets, leading to increased destruction of platelets in the spleen and decreased platelet count. If the platelet count decreases to less than 100,000/μL, ITP is suspected. The clinical symptoms of ITP include subcutaneous bleeding (petechiae or purpura) as well as bleeding from the gums or nose, blood in urine or stools, and intracranial bleeding. Generally, patients with platelet counts of 50,000/μL or less show an apparent bleeding tendency. The disease is treated with corticosteroids or thrombopoietin (TPO) receptor agonists and surgical removal of the spleen. The number of patients with ITP is estimated to be about 25,000^※ in Japan.

*3: Autoimmune hemolytic anemia (AIHA)

The production of autoantibodies that react with antigens on erythrocyte membranes results in antigen-antibody reaction, which leads to injury and remarkably shortened lifespan of erythrocytes (hemolysis). This eventually causes anemia. AIHA is a designated intractable disease. The number of patients with AIHA is estimated to be about 800^※ in Japan.

*4: IgA nephropathy

The disease presents with urinary findings (glomerular hematuria, positive urine protein test) suggesting the signs of nephritis and predominant IgA deposition in the glomeruli, but no underlying disease that is likely to be the cause. It is a designated intractable disease. The number of patients with IgA nephropathy is estimated to be about 6,500^※ in Japan.

^※: Based on the number of recipients of the certificates for special disease treatment in 2016.


About Rigel Pharmaceuticals, Inc.（www.rigel.com）

Rigel Pharmaceuticals, Inc., is a biotechnology company dedicated to discovering, developing and providing novel small molecule drugs that significantly improve the lives of patients with immune and hematologic disorders, cancer and rare diseases. Rigel's pioneering research focuses on signaling pathways that are critical to disease mechanisms. The company's first FDA approved product is TAVALISSE™ (fostamatinib disodium hexahydrate), an oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. Rigel's current programs include an upcoming Phase 3 study of fostamatinib in autoimmune hemolytic anemia and an ongoing Phase 1 study of R835, a proprietary molecule from its interleukin receptor associated kinase (IRAK) program. In addition, Rigel has product candidates in development with partners BerGenBio AS, Daiichi Sankyo, and Aclaris Therapeutics.