Kirin Holdings Co., Ltd.
Kirin Holdings engages in alcohol beverages, non-alcohol beverages, and pharmaceuticals
and bio-chemicals business.
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The Pharmaceuticals and Bio-chemicals business includes:o Kyowa Hakko Kirin Co. Ltd.
o ProStrakan Group plc → now known as Kyowa Kirin (since April 18, 2016)o Kyowa Hakko Bio Co., Ltd.
o Kyowa Kirin FrontieroPharmaceutical businesses they have outside of Japan:• Kirin-Amgen, Inc. (U.S.)• Gemini Science, Inc. (U.S.)• Hematech Inc. (U.S.)• Jeil-Kirin Pharmaceutical, Inc. (South Korea)• Kirin Pharmaceuticals Company, Ltd. (Taiwan)• Kirin Pharmaceuticals (Asia) Company, Ltd. (Hong Kong)• Kirin Kunpeng Bio-Pharmaceutical Company, Ltd. (China)
Kyowa Hakko Kirin Co., Ltd. – a pharmaceutical and biotechnology that centers on
antibody engineeringhttps://www.kyowakirin.com• Conducts development, manufacturing and sales of drugs and therapeutic
antibodies based on bio-technology• Focus on areas of oncology, nephrology, central nervous system, and immunology• They offer products related to amino acids and nucleic acids in the fields ofpharmaceuticals, medicine, and healthcare• General company details:
o Is among the 40 largest in the world by revenue
o Founded in 1949
o Number of employees: Over 7000
o Annual revenue: 346 billion yen
o Operating profit: 58 billion yen
o Currently they have 4 antibody drugs released and 4 in pipelineo Chairman: Nobuo Hanai
o President and CEO: Masashi Miyamotoo Offices in Japan, U.S., Uk, China, Korea• Financial results:
https://ir.kyowakirin.com/en/library/earnings.html?_ga=2.218859153.960152318.
1565187855-903805719.1565187855#19q2• The company developed a method to make afucosylated monoclonal antibodies
using a CHO cell line in which FUT8 has been knocked out → the company calls thisits “POTELLIGENT” platform••o The company gained marketing approval in Japan in April 2012 for a
monoclonal antibody drug called mogamulizumab which was developed
using this platformo Mogamulizumab is used for the treatment of relapsed or refractory adult Tcell leukemia/lymphoma and relapsed or refractory cutaneous T cell
lymphoma (approved in 2014)
They focus on technology-driven drug discovery based on 4 key modalities:o Next Generation Therapeutic Antibodies▪ The fundamental technologies of Kyowa Kirin in the production oftherapeutic antibodies are characterized by POTELLIGENT andhuman-antibody producing mice technologies▪ They are engaged in research and development of next generation
therapeutic antibodies
o New Types of Small Molecule Drugs▪ Their approach to small molecule drug discovery involves rational
drug design → structure-based drug design ranging from thestructural analysis of disease-associated biomolecules (therapeutictarget) to the design of small molecules
o Nucleic Acid Drugs▪ Kyowa Hakko is actively working on the development of nucleic aciddrugs which are attracting attention as new therapy
o Regenerative Medicine
They currently have numerous drug candidates in the works
o Ex. KHK4827 to treat Psoriasis

Main products:• ESPO/NESP – an erythropoiesis stimulating agent (ESA) with longer-lasting effectthan conventional erythropoietin drugs
o Effective for improving renal anemia• REGPARA – a new class of agent for the treatment of secondary
hyperparathyroidism
o Acts on parathyroid calcium receptor directly and suppresses parathyroid
hormone secretion, while lowering serum calcium and phosphorus levels• GRAN/Peglasta/Neulasta – a human colony-stimulating factor (G-CSF) produced bygenetic recombination technology
o Works to selectively increase the count and functional efficacy of a type ofwhite blood cell called neurotrophil• Romiplate/Nplate – a genetically recombinant protein
o Stimulates platelete production via stimulation of the thrombopoietin
receptors• Crysvita – a recombinant fully human monoclonal lgG1 antibody against thephosphaturic hormone fibroblast growth factor 23
o By blocking excess FGF23 in patients, this drug intends to increase phosphatereabsorption in the kidney and increase the production of vitamin D•o This enhances intestinal absorption of phosphate and calcium in patientswith X linked hypophosphatemia
Poteligeo – a humanized monoclonal antibody that targets CC chemokine receptor 4(CCR4) which is frequently expressed in leukemic cells

Kyowa Kirin International plc – a subsidiary of Kyowa Hakko Kirin Co. Ltd.
https://www.kyowakirin.com• In 2011, Kyowa Hakko Kirin Co. Ltd bought Scottish drug firm ProStrakan Group Plc
for $474.6 milliono This allowed Kirin to establish European and U.S. sales platforms as well as a
Suite of specialist prescription products• Engages in administration and management of subsidiaries under• Acquired Archimedes Pharma from the Novo Nordisk Foundation for $394 million
on July 11, 2014
Kyowa Hakko Bio Co., Ltd. – subsidiary of Kyowa Hakko Kirin Co. Ltd.
http://www.kyowahakko-bio.co.jp/english/••••

Established in 2008
Capital of 10,000 million yen and revenue of 81.1 billion yen
President: Takeshi Minakata
Goal: to be a biochemical innovator that provides clients with products and services
to fulfill their healthcare needs, using their deep knowledge of fermentation andsynthesis• Offices in Tokyo, New York, Germany, Italy, Singapore, India, and multiple in China• They are engaged in the manufacturing and sales of pharmaceutical and industrial
raw materials and healthcare products, among otherso Ex of raw materials: amino acids, peptides, oligosaccharides, nucleic acids
o Supplies high quality materials such as amino acids, nucleic acids anddipeptides which are essential for pharmaceuticals, dietary
supplements/foods, and cosmetics
o Provide high quality bulk API (Active Pharmaceutical Ingredient) topharmaceutical companies around the world
o They also actively develop new products in collaboration withpharmaceutical companies to expand their base of operations• The company sets out to respond to the global demand for high-value amino acids
due in part to rising levels of healthcare and call for generic drugs• In 1956, Kyowa Hakko Kirin became the first company in the world to succeed in theindustrial production of amino acids using fermentation methodso Since then, Kyowa Hakko Bio has released a wide range of amino acids andhas been a global leader in the field• Kyowa Hakko Bio has discovered an enzyme with dipeptide synthesizing activity →this enzyme reacts with a variety amino acids to yield multifarious dipeptides
Kyowa Kirin Frontier Co., Ltd.

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Established in January 2017 as part of the “Creating Shared Value management
based on unique business structure” within the Contribution to Health and Wellbeing of People, which was one of the core strategies set forth by Kyowa Kirin
They work toward obtaining approval to manufacture and market authorizedversion of NESP
Estimated capital in 2017: 100 million yen

NewsKyowa Kirin Buys Back Tivozanib Non-Oncology Rights from AVEO Oncology – Aug 1, 2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190801_01.html• Kyowa Kirin and AVEO Oncology announced that they have amended their license
agreement to allow Kyowa Kirin to buy back the non-oncology rights of tivozanib in
AVEO territories, excluding the rights which are currently sublicensed to EUSA
Pharmao Tivozanib is an oral, vascular endothelial growth factors tyrosine kinase
inhibitor discovered by Kyowa Kirin → approved for the treatment of adultpatients with advanced renal cell carcinoma• Kyowa Kirin is obligated to an upfront payment of $25 million to AVEO and up to$391 million in potential milestone payments upon successful achievement ofcertain objectives in non-oncology indications of tivozanibo Kyowa is also obligated to make tiered royalty payments on the net sales ofthese indicationso Agreement also waives AVEO’s obligation to make an $18 million milestone
payment upon AVEO gaining the U.S. marketing approval
Kirin Announces Launch of Darbepoetin Alfa Injection syringe in Japan – July 30, 2019https://www.marketscreener.com/KYOWA-HAKKO-KIRIN-CO-LTD-6491339/news/KyowaHakko-Kirin-Notice-Regarding-Change-of-Trade-Name-Partial-Amendments-to-theArticles-of-Inc-27064755/• Announced on July 30th, 2019 that its wholly owned subsidiary Kyowa Kirin FrontierCo., Ltd. will launch Darbepoetin Alfa Injection Syringe in Japan on August 5o Darbepoetin Alfa Injection Syringe was approved in Japan on Aug 15, 2018
and is an authorized version of NESPo This will help patients with Chronic Kidney Disease (CKD)
Kyowa Hakko Kirin Receives Partial Approval of Romiplate for Aplastic Anemia in Japan –June 18, 2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190618_01.html• Romiplate (AMG531) is a treatment of aplastic anemia (AA) in patients who have
had an inadequate response to conventional therapy• It was launched for the treatment of idiopathic thrombocytopenic purpura (ITP) andhas contributed to many ITP patients since April 2011
Kyowa Hakko Kirin Announces Top-Line Results of Phase 3 Study of Brodalumab(KHK4827) in Patients with Axial Spondylarthritis – June 17, 2019

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The company announced positive results of a 16-week efficacy and safety analysis of
the phase 3 study of Brodalumab in patients with axial spondylarthritis and nonradiographic axial spondylarthritis
The study showed that more patients who were given Brodalumab showed an
improvement of equal to or above 40% and an absolute improvement of above or
equal to 2 units compared to the control group ay week 16
o There were also no apparent differences in safety between the 2 groups
This showed that Brodalumab was well tolerated in 16 weeks and effective for thetreatment of axSpA
Study was conducted in Japan, South Korea, and Taiwan

Kyowa Hakko Kirin Launches Mirai Port – June 13, 2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190613_01.html• The company launched its new Sustainable Development Goals (SDGs) website,
Mirai Port to raise awareness of SDGs and the company’s actions
Kyowa Hakko Kirin Submits the Partial Change Approval Application of KHK7580(evocalet) in Japan – April 24, 2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190424_01.html• The company announced that they submitted a supplemental application of
KHK7580 (evocalcet) for the treatment of hypercalcemia in patients withparathyroid carcinoma or primary hyperparathyroidism who are unable to undergo
parathyroidectomy or relapse after it, to the Ministry of Health, Labor and Welfare inJapan• This application was based on the results of the phase 3 study that evaluated theefficacy of KHK7580• KHK7580 was also granted Orphan Drug Designation for the treatment of this groupof patients by the Ministry of Health, Labor and Welfare on March 4, 2019
Kyowa Kirin Announces FDA Acceptance of Istradefylline (KW-6002) – April 4, 2019https://www.kyowakirin.com/media_center/news_releases/2019/pdf/e20190404_01.pdf• Kyowa Hakko Kirin announced that the U.S. FDA has accepted froe review theresubmitted New Drug Application for istradefylline (KW-6002) – an investigational
selective adenosine for use as adjunctive treatment to levodopa/carbidopa in adultpatients with Parkinson’s disease experiencing “off” episodes

Kyowa Hakko Kirin Enters New Development and Commercialisation Agreements with
AstraZeneca for All Benralizumab Indications beyond COPD and Asthma in Asia – March 25,
2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190325_01.html• Kyowa Kirin announced that they have entered a new agreement with AstraZeneca,
granting AstraZeneca exclusive rights to benralizumab (brand name Fasenra) for all
additional indications in Asia, inclusive of Japan•••o AstraZeneca now has global rights to benralizumab for all current and futureindications
Under the agreement, AstraZeneca will pay Kyowa Hakko Kirin up-front andsubsequent payments for regulatory and commercial milestones
AstraZeneca will now be responsible for development, sales, and marketing of
benralizumab for all indications in 14 Asian countries and regions
Benralizumab is now approved as an add-on maintenance treatment in severe,eosinophilic asthma in the US, EU, Japan, and several other jurisdictions

Kyowa Kirin Asia Pacific Announces Establishment of Subsidiary in Australia – March 18,
2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190318_01.html• Kyowa Kirin Asian Pacific Pte. Ltd (a wholly owned subsidiary of Kyowa Hakko Kirin
CO., Ltd.) announced that it has established an Australian subsidiary, named Kyowa
Kirin Australia Pty Ltd.
o Which this expansion they aim to launch Kyowa Hakko Kirin’s global strategic
products into Australia
Ultragenyx and Kyowa Kirin Announce Positive 64-Week Results for Crysvita (burosumab)from Phase 3 Study in Children with K-linked Hypophosphatemia – Feb 15, 2019https://www.kyowakirin.com/media_center/news_releases/2019/pdf/e20190215_01.pdf• Results showed that Crysvita was superior to conventional therapy for all key
efficacy endpoints• Crysvita is an antibody that blocks fibroblast growth factor 23 – a hormone thatcauses an excess of phosphate urinary excretion and suppresses active vitamin D
production by the kidney
Kyowa Hakko Kirin Initiated Phase 2 Clinical Study of Tenapanor (KHK7791) for
Hyperphosphatemia Patients on Hemodialysis in Japan – Feb 6, 2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190206_01.html• Phased 2 clinical study was initiated in Japan for tenapanor – a small moleculecompound licensed from Ardelyx, Inc.
o Tenepanor is an oral, minimally systemic NHE3 inhibitor with a uniquemechanism that is different from the current phosphate binder therapy• Phase 2 sets out to evaluate serum phosphorus in hyperphosphatemia patients on
Hemodialysis who switch from phosphate binders to KHK7791 in Japano The study will evaluate the efficacy and safety of a switch from phosphatebinders to KHK7791• Kyowa Hakko Kirin also plans to initiate 2 additional phase 2 clinical trials for
KHK7791 0o A monotherapy dose-response study and a combination therapy with
KHK7791 and phosphate binders• Kyowa Hakko Kirin signed a license agreement with Ardelyx for the exclusive rights
to develop and commercialize tenapanor in cardiorenal disease in Japan on
November 28, 2017

Hisamitsu Pharmaceutical and Kyowa Hakko Kirin sign Commercialization Agreement for
HP-3000 (a Potential New Transdermal Patch for Parkinson’s Disease in Japan) – Feb 5,
2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190205_02.html• The two companies entered an agreement granting Kyowa Hakko exclusive rights tocommercialize HP-3000
o Kyowa Hakko will be responsible for commercializing the product afterHisamitsu Pharmaceutical receives a manufacturing and marketing approval
for the product in Japan• The product is a systematic transdermal Parkinson’s disease treatment patch
developed by Hisamitsu Pharmaceutical’s TDDS technologies• Hisamitsu Pharm will receive an upfront payment and milestone payments based on
the regulatory approval and sales amount
Kyowa Hakko Kirin Announces Changes in Global Management Structure – Feb 5, 2019https://www.kyowakirin.com/media_center/news_releases/2019/pdf/e20190205_05.pdf• The company announced changes to its global management structure to “One Kyowa
Kirin” effective April 1, 2019o Under this new structure, Kyowa Kirin Group will be organized both byregion and function• Kyowa Kirin USA Holdings Inc. will be responsible for North America’s market• Kyowa Kirin International PLC will in the future, be responsible for the Europe,
Middle East, and Africa market• A Global Product Management Office will be newly established directly under thecontrol of president of Kyowa Hakko Kirin to unify the management of Kyowa Kirin
Group’s global strategic productso Tomohiro Sudo, currently VP of Kyowa Kirin International PLC was appointed
as the new Head of Global Product Management Office
Kyowa Hakko Kirin Submits Application for Approval of Burosumab in Japan – January 7,
2019https://www.kyowakirin.com/media_center/news_releases/2019/e20190107_01.html• The company filed an application for manufacturing and marketing approval withJapan’s Ministry of Health, Labor and Welfare for burosumab to treat FGF23-related
hypophosphatemic rickets and osteomalacia
o Burosumab is antibody that was discovered by Kyowa Kirin and wasdeveloped to treat FGF23-related hypophosphatemic disease such as x-linked
Hypophosphatemia and tumor-induced osteomalacia/epidermal nevus
Syndromeo Burosumab is designed to bind to and thereby inhibit the biological activityof FGF23 → by doing so, it increases phosphate reabsorption from the kidney
and increases the production of vitamin D, which enhances intestinal
absorption of phosphate and calcium• Burosumab received orphan drug designation in Japan••The company expects to receive feedback regarding manufacturing and marketing
approval for burosumab around September 2019
Kyowa Hakko Kirin, Kyowa Kirin International PLC, and Ultragenyx Pharmaceutical
Inc. has been collaborating in the development and commercialization of burosumab
globally

Ultragenyx and Kyowa Kirin Announce Health Canada Approval of Crysvita (burosumab
injection) for the Treatment of X-linked Hypophosphatemia in Adults and Chidlren – Dec 6,2018https://www.kyowakirin.com/media_center/news_releases/2018/e20181206_01.html• The product is expected to be available for prescription to Canadian patients in early2019• This offers patients with XLH the first treatment option that targets the underlying
cause of their rare disease• Crysvita is now approved in the US, Europe, and Canada• Burosumab is the first treatment to address the fundamental problem in this disease– renal phosphate wasting
Kyowa Kiririn Announces POTELIGEO Receives Marketing Authorisation in Europe –November 26, 2018https://www.kyowakirin.com/media_center/news_releases/2018/e20181126_01.html• POTELIGEO will be the first biologic agent targeting chemokine receptor 4 (CCR4) to
be available for patients with mycosis fungoides or Sezary Syndrome n Europeo Mycosis fungoides (MF) and Sezary Syndrome (SS) are the 2 most common
subtypes of cutaneous T-cell lymphoma• Kyowa Kirin plans to launch POTELIGEO in various markets in Europe from 2019o Kyowa Kirin International PLC will be responsible for commercialising
POTELIGEO in Europe
GSK and Kyowa Hakko Kirin sign strategic commercialisation deal in Japan for daprodustat,a potential new oral treatment for anaemia associated with chronic kidney disease – Nov22, 2019
https://www.kyowakirin.com/media_center/news_releases/2018/e20181122_01.html• The two companies announced a strategic collaboration for the futurecommercialisation of daprodustat in Japano Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor
currently in phase 3 development by GSK for the treatment of anaemia
associated with chronic kidney disease• GSK will be responsible for the completion of the ongoing phase 3 clinicalprogramme and regulatory submissions for marketing authorisation in Japan• Distribution of daprodustat will be conducted by Kyowa Hakko Kirin• Positive results from two phase 3 studies in dialysis dependent Japanese patientswere recently announced

MEI Pharma and Kyowa Hakko Kirin Announce License Agreement to Develop andCommercialize ME-401 in Japan – Nov 5, 2018https://www.kyowakirin.com/media_center/news_releases/2018/e20181105_01.html• This agreement granted Kyowa Hakko Kirin exclusive rights to develop andcommercialize ME-401 in Japano MEI is a treatment for patients with B-cell malignancies
Kyowa Hakko Kirin Announces a Phase 1 Clinical Study of its IDO Inhibitor in Solid Tumor 0
Nov 2, 2018https://www.kyowakirin.com/media_center/news_releases/2018/e20181102_01.html• Kyowa Hakko Kirin entered a collaboration agreement with Merck kGaA, Darmstadt,
Germany and Pfizer to initiate a Phase 1 clinical study of Kyowa Hakko Kirin’s novel
IDO inhibitor, KHK2455, in combination with avelumab (a human anti-PD-L1
antibody for solid tumors)• Kyowa Hakko will initiate a Phase 1 clinical study in the US• Avelumab has received accelerated approval by the FDA for the treatment of patientswith metastatic Merkel cell carcinoma (MCC) and previously treated patients withlocally advanced or metastatic urothelial carcinoma (mUC) and is under further
evaluation across a range of tumor types
o However, Avelumab is under clinical investigation for treatment of solid
malignancies and has not been demonstrated to be safe and effective forthese uses
Mylan and Fujifilm Kyowa Kirin Biologics Receive European Marketing Authorization for
Hulio – Sep 20, 2018
• MylaN.V. and Fujifilm Kyowa Kirin Biologics Co. Ltd announced that the European
Commission has granted marketing authorization for Hulio → a biosimilar to
AbbVIe’s Humira (the world’s best-selling biologic medication)o This follows the adoption of a positive opinion by the Committee for
Medicinal Products for Human Useo This approval applies to all 23 EU countries and the European Economic Area
member states• Mylan plans to launch Hulio across various markets in Europe on or after Oct 16• Hulio is indicated for the same indications of Humirao Ex. rheumatoid arthritis, psoriasis, Crohn’s disease
Kyowa Hakko Kirin Announces Results of Early Phase 2 Trial of KW-6356 for Parkinson’s
Disease – Aug 20, 2018https://www.kyowakirin.com/media_center/news_releases/2018/e20180820_01.html• The study showed that KW-6356 monotherapy is well tolerated and effective in thetreatment of motor symptoms in early PD patients• The company plans to initiate late phase 2 clinical trial in Japan by the end of 2018
• KW-6356 is a selective antagonist of adenosine A2A receptors developed by Kyowa
Hakko Kirin

FDA Approves of Poteligeo for the Treatment of Mycosis Gunfoides and Sezary Syndrome –Aug 9, 2018https://www.kyowakirin.com/media_center/news_releases/2018/e20180809_01.html• FDA granted approval for Poteligeo for the treatment of adult patients with relapsed
or refractory mycosis fungoides or Sezary syndrome after at least 1 prior systemic
therapy• Using the proprietary POTELLIGENT technology, the amount of fucose in the sugar
chain structure of Poteligeo is reduced → this enhances the antibody dependent
cellular cytotoxicity• FDA granted Poteligeo Breakthrough Therapy Designation for the treatment of MF
and SS in adult patients and evaluated Poteligeo with Priority Review
o This is reserved for drugs that treat a serious condition and if approved,
would provide a significant improvement in treatment safety or effectiveness• Kyowa Kirin International PLC and Kyowa Hakko Kirin Co. will be responsible forcommercializing Poteligeo in the U.S.
http://globalmarketnews24.com/32991/global-asparaginase-market-2019-kyowa-hakkokirin-alize-pharma-jinan-welcome-biochemical-pharmaceutical/• Kyowa Hakko Kirin was listed as one of the leading Asparaginase Industry players in
the Global Asparaginase Market 2018 Research Reporthttps://pledgetimes.com/2019/08/09/animal-based-food-amino-acid-market-swotanalysis-and-surge-from-2019-2025-ajinomoto-inc-japan-kyowa-hakko-kirin-group-japansigma-aldrich-co-llc-u-s/• Kyowa Hakko Kirin was listed as one of the top prominent players the Global
Animal-based Food Amino Acid Market Research Reporthttps://industrynewsfeed.com/24285/global-drugs-for-non-small-cell-lung-cancermarket-2019-kyowa-hakko-kirin-hikma-pharmaceuticals-curis/• Kyowa Hakko Kirin is recognized as one of the top manufacturers for the Non-Small
Cell Lung Cancer Market