Amgen and Kyowa Kirin to Jointly Develop and Commercialize KHK4083, a Phase 3-Ready, Potential First-In-Class Treatment for Atopic Dermatitis

• Agreement Renews Successful Global Collaboration That led to Several Groundbreaking Therapies in Multiple Disease Areas
• KHK4083 Depletes OX40-Expressing T cells Associated with Atopic Dermatitis and Several Other Inflammatory Diseases
• Moderate-to-Severe Atopic Dermatitis Affects Nearly 30 Million People in Major Global Markets¹
• Amgen to Host Investor Call at 8:00 a.m. EST

Amgen (NASDAQ: AMGN) and Kyowa Kirin Co., Ltd. (TSE: 4151) today announced an agreement to jointly develop and commercialize KHK4083, which is Kyowa Kirin's potential first-in-class, Phase 3-ready anti-OX40 fully human monoclonal antibody in development for the treatment of atopic dermatitis, with potential in other autoimmune diseases. In February, Kyowa Kirin announced positive results from a Phase 2 study of KHK4083 in patients with moderate-to-severe atopic dermatitis, which affects nearly 30 million people in major global markets¹. 

Under terms of the agreement, Amgen will lead the development, manufacturing, and commercialization for KHK4083 for all markets globally, except Japan, where Kyowa Kirin will retain all rights.  Additionally, Kyowa Kirin will co-promote KHK4083 with Amgen in the U.S. and have opt-in rights to co-promote KHK4083 in certain other markets outside the U.S., including in Europe and Asia.  Amgen will make a $400 million up-front payment to Kyowa Kirin and future contingent milestone payments potentially worth up to an additional $850 million, as well as significant royalty payments on future global sales.  Kyowa Kirin and Amgen will share global development costs, except in Japan, and U.S. commercialization costs.  Amgen will consolidate sales for KHK4083 in all markets globally, except for Japan.  Amgen also will leverage unique data from its deCODE Genetics subsidiary to inform the potential use of KHK4083 in indications beyond atopic dermatitis.  The closing of the transaction is conditioned on obtaining any necessary consents and approvals.

"Kyowa Kirin has a long legacy of partnering with other companies to deliver the full value of our scientific discoveries and novel medicines for patients," says Masashi Miyamoto, Ph.D., president and chief executive officer at Kyowa Kirin. "KHK4083 is an important asset in our global pipeline. We know Amgen well, and this alliance will build on the past success and trust we have, bringing additional resources and therapeutic expertise to KHK4083's development and commercialization, to meet the needs of patients living with atopic dermatitis who seek alternative treatment options."

KHK4083 is an anti-OX40 fully human monoclonal antibody discovered by Kyowa Kirin and engineered with Kyowa Kirin's patented POTELLIGENT® defucosylation technology to enhance its antibody-dependent cellular cytotoxicity (ADCC) activity.  KHK4083 has been shown to selectively deplete activated T cells that are critical in the development of atopic dermatitis.  Kyowa Kirin antibodies powered by POTELLIGENT technology with ADCC activity are currently marketed in therapeutic areas including Oncology and Asthma. This potent antibody-enhancement platform is also licensed to numerous third parties throughout the biopharmaceutical industry.

"Kyowa Kirin was one of Amgen's very first collaborators and we are delighted to be joining forces with them once again to advance this promising late-stage asset to treat atopic dermatitis," said Robert A. Bradway, chairman and chief executive officer at Amgen.  "We will take advantage of our two decades of experience in inflammatory disease, as well as our industry-leading human genetics capabilities, to help realize the full potential of KHK4083 as quickly as possible."

Amgen is a global leader in treating inflammatory diseases, with a portfolio of marketed medicines that includes Otezla®, Enbrel®, AMGEVITA® (a biosimilar to Humira®), and AVSOLA® (a biosimilar to Remicade®).  Amgen's pipeline of investigational therapies includes tezepelumab (filed for U.S. FDA approval in May 2021 as a potential first-in-class treatment for severe asthma), ABP 654 (a biosimilar to STELARA®), and several innovative molecules in Phase 2b development for systemic lupus erythematosus and celiac disease. 

"KHK4083 is another example of our world-leading expertise in antibody engineering, applied target selection and optimization. We are proud to be a science-led organization whose research capabilities continue to produce meaningful discoveries, while also taking advantage of open innovation, that offers potential for improving treatment paradigms," said Yoshifumi Torii, Ph.D., executive officer, vice president, Head of Global R&D Division at Kyowa Kirin. "Results from clinical trials for KHK4083, including Phase 2 data, show great promise and we look forward to initiating a late-stage global program with Amgen to deepen our understanding of this asset."

In 1984, Amgen and Kirin Holdings Co., Ltd (former Kirin Brewery Co., Ltd), the parent company of Kyowa Kirin, established a 50-50 joint venture to develop and commercialize EPOGEN® (Japanese brand name: ESPO®), which, in 1989, became the first Amgen medicine approved in the U.S., and, in 1990, became the first Kirin medicine approved in Japan.  Over time, the joint venture expanded to include the development and commercialization of several other medicines, including NEUPOGEN® (GRAN® in Japan), Neulasta® (G-Lasta® in Japan), Aranesp® (NESP® in Japan), and Nplate® (Romiplate® in Japan).  In 2017, the companies announced that the joint venture would become a wholly owned subsidiary of Amgen, with Kyowa Kirin in-licensing certain Amgen medicines in the Asia-Pacific region. 

Amgen Webcast Investor Call

Amgen will host a webcast call for the investment community on June 1, 2021, at 8:00 a.m. EST. Peter H. Griffith, executive vice president and chief financial officer, David M. Reese, M.D., executive vice president of Research and Development, and Murdo Gordon, executive vice president of Global Commercial Operations at Amgen will participate. 

Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public. The webcast, as with other selected presentations regarding developments in Amgen's business given at certain investor and medical conferences, can be accessed on Amgen's website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event. 

About the KHK4083 Phase 2 Study

In February 2021, Kyowa Kirin reported that KHK4083 met the primary endpoint in a Phase 2 randomized, double-blind and placebo-controlled clinical study conducted in the U.S., Japan, Canada, and Germany.  The study included 274 patients with moderate-to-severe atopic dermatitis, who were not adequately controlled with topical agents.  All KHK4083 cohorts achieved superiority to the placebo cohort for the primary endpoint of percent change from baseline in Eczema Area and Severity Index (EASI) at 16 weeks with statistical significance. In addition, there was significant difference in the percentage of patients achieving an EASI-75 (EASI score of 75% or greater improvement from baseline) at 16 weeks and the percentage of patients achieving the Investigator's Global Assessment (IGA) of 0 or 1 with an improvement of 2 points or more at 16 weeks in all KHK4083 cohorts compared to the placebo cohort. Sustained  efficacy of KHK4083 was observed beyond week 16.

Common treatment-emergent adverse events for KHK4083 cohorts were pyrexia, nasopharyngitis, worsening of atopic dermatitis and chills during the first 16 weeks. Pyrexia and chills events were mild to moderate in intensity, most of them were due to injection reaction and observed only after the first administration of the investigational product. There were no events of severe hypersensitivity reactions and no deaths observed in the study.

About Atopic Dermatitis

Atopic dermatitis is a chronic disease in which the immune system becomes disordered and overactive, triggering inflammation that damages the skin barrier.  People with atopic dermatitis can get rashes anywhere on the body that can ooze, weep fluid and bleed when scratched, making skin vulnerable to infection. Skin can become dry and discolored, and repeated scratching can cause thickening and hardening of the skin.  Atopic dermatitis typically begins in childhood, affecting 15% to 20% of children and 1% to 3% of adults worldwide.  The incidence of the disease has increased two- to three-fold since the 1970s.  People who have asthma and/or hay fever or who have family members who do, are more likely to develop atopic dermatitis.

About OX40

OX40 is a co-stimulatory molecule that is one of the tumor necrosis factor receptor (TNFR) family members.  It plays an important role in maintaining T cell proliferation and survival and in the formation of memory T cells.  OX40 is expressed on the surface of effector T cells (CD4 positive) activated by antigens.  It has been reported that effector T cells expressing OX40 are present in the lesions of atopic dermatitis.

About Kyowa Kirin

Kyowa Kirin strives to create and deliver novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company with a more than 70-year heritage, the company applies cutting-edge science including an expertise in antibody research and engineering, to address the needs of patients and society across multiple therapeutic areas including Nephrology, Oncology, Immunology/Allergy and Neurology. Across our four regions – Japan, Asia Pacific, North America and EMEA/International – we focus on our purpose, to make people smile, and are united by our shared values of commitment to life, teamwork/Wa, innovation, and integrity. You can learn more about the business of Kyowa Kirin at: https://www.kyowakirin.com.

About Amgen

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. 

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. 

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.