2019 Progress

Expanding R&D pipeline and investments
In 2019, Takeda had more than 5,000 R&D employees worldwide, working together to advance new treatment options. We invested ¥492.4 billion in R&D and established 38 new R&D collaborations with biotech and academia, adding to the more than 200 active partnerships already in place.

Takeda’s R&D organization has produced exciting new molecular entities (NMEs) that represent potential best-in-class and/or first-in-class medicines in areas of high unmet need. We’ve also extended our leadership by growing Takeda’s focus and dedication to rare diseases in our efforts to build trust and reputation in the community as true partners and leaders in rare diseases.

Innovative Biopharma
Innovative Biopharma is the largest component of Takeda’s R&D investment and has produced approximately 40 NMEs that are now in our pipeline across our core therapeutic areas of Oncology, Rare Genetic and Hematology, Neuroscience and Gastroenterology. We pursue diseases in therapeutic areas with existing expertise and knowledge and collaborations. These are often diseases in targeted and rare patient populations.

Takeda has established a dynamic pipeline that includes 12 NMEs in Wave 1 that are intended to fuel our growth trajectory while our next-generation platforms mature in Wave 2. All 12 NMEs in Wave 1 have transformative potential for patients, representing the high innovation bar our R&D organization has established, positioning us to deliver several important medicines in the near future. For example:

• TAK-721 is a small molecule in development for the treatment of eosinophilic esophagitis (EoE). EoE is a rare, chronic, inflammatory disease characterized by raised eosinophils — or disease-fighting white blood cells — in the esophagus. This results in difficulty and pain when swallowing food, and in severe cases, can lead to food becoming stuck in the esophagus. TAK-721 has the potential to be the first FDA-approved medicine to treat EoE.
• Pevonedistat is a potential first-in-class therapy for the treatment of two forms of rare bone marrow-related cancers, higher-risk myelodysplastic syndrome (HR-MDS) and acute myeloid leukemia (AML). HR-MDS and AML are related forms of rare cancer, sharing similar foundation biology and genetic mutations. Approximately 40% of patients with HR-MDS transform to AML, an aggressive form of acute leukemia in adults, with poor outcomes. If approved, pevonedistat could become the first novel treatment for HR-MDS patients in more than a decade.
• Mobocertinib is a small molecule in development for the treatment of a subset of non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations for which there are no approved treatments. Mobocertinib is designed to selectively target EGFR and HER2 exon 20 insertion mutations and has potential to change the standard of care for this patient population.
• Maribavir is a potential best-in-class treatment for post-transplant infection caused by cytomegalovirus (CMV) after undergoing hematopoietic cell transplant or solid organ transplant. CMV is a virus that, in patients with compromised immunity, causes clinically challenging complications that can be fatal. Maribavir targets a specific protein known as CMV UL97 protein kinase, which may stop CMV DNA from replicating and prevent the virus from spreading to other cells.

Employees across Takeda R&D are advancing these and other near-term catalysts with a sense of urgency while building our next-generation platforms to sustain our long-term growth. Together, we aim fulfill our purpose to deliver Better health for people, brighter future for the world.

Plasma-derived therapies (PDT)
Even with the major advances of the last 75+ years, we believe there is an incredible untapped opportunity to innovate in PDT for the benefit of patients worldwide. In 2019, Takeda developed an end-to-end PDT strategy and created a dedicated team and budget to look at how we could reimagine plasma from collection through production to delivery. We’re not only extending the therapeutic potential of our existing therapies, but also innovating how we use PDTs to improve the health of the patients we aim to serve.

We’re fostering a culture of innovation in PDT R&D through two engines:

• Translational Pharmaceutical Sciences. A merged research focus on translational research, pharmaceutical science and devices. This engine aims to create value by generating new investigational candidates, challenging mechanisms of action, identifying responder populations, and improving or creating new development pathways.
• Integrated Care Solutions. A research engine enhancing the value of our therapies beyond the medicines themselves into complete care solutions. This engine is focused on improving health outcomes by improving diagnostic rates and specificities, assessing new point of care solutions, including medicine delivery, and expanding datasets to demonstrate the effectiveness of our therapies, illustrating value not only to providers, but to payors as well.

Along with the above, the PDT R&D strategy targets three additional areas of focus:

• Realizing the full potential of our current portfolio. Building on a legacy of innovation and leadership in PDT, we are actively working to expand indications for our current product lines. We’re adding new data to define their value, building diagnostic and device applications, expanding geographically, and researching new formulations and delivery approaches, including collaboration with patient communities to identify value and outcomes that are meaningful for patients.

• Optimizing efficiencies of plasma-derived therapy production. We also create dynamic innovation by employing pharmaceutical science within our global manufacturing processes. Today’s global immunoglobin and albumin supply challenges are disruptive for patients. As Takeda works to increase supply, R&D is contributing to this by designing production efficiencies that can improve our throughput and yield. These initiatives include process development activities to shorten IgG upstream cycle times and total albumin cycle times. A useful byproduct of this work is the purification process waste we capture, from which we can isolate additional proteins for possible new development. From these improvements, we aim to achieve higher yield, increased capacity and significantly reduced cost of goods sold.
  
  
• Identifying and developing new plasma-derived therapies. We believe there’s tremendous untapped therapeutic potential in plasma proteins for a wide variety of acute and chronic diseases. For instance, there are more than 3,000 plasma proteins in the human body, some with health-promoting effects and others with disease-associated effects, and only a fraction are therapeutically applied today. While PDT are typically used to replace protein deficiencies, there may be opportunities in settings where there is an imbalance of health-promoting and disease-associated proteins.

In the age of recombinant proteins, gene therapies and other novel modalities, we believe there are persistent needs that can only be effectively addressed with PDT. We will continue to use our integrated capabilities to identify and deliver within those niche areas.

There are more than 3,000 plasma proteins in the human body, some with health-promoting effects and others with disease-associated effects, and only a fraction are therapeutically applied today.

Global vaccine development

We’re developing new vaccines to address some of the world’s most pressing public health needs. Our Vaccine Business Unit (VBU) has developed a pipeline that focuses on diseases that impact regions around the world, including low- and middle-income countries (LMICs) that might be disproportionally affected. The VBU’s aim is to make vaccines available in countries with the highest unmet need, fully develop and register them and build capacity within our facilities to produce the millions of doses that are required to improve global health. Currently, vaccine efforts are focused on:

• Dengue. Approximately half of the world’s population is at risk for dengue, the fastest-spreading mosquito-borne viral disease in the world, and one of the World Health Organization’s (WHO) top 10 threats to global health in 2019. We’re currently conducting an ongoing, pivotal Phase 3 clinical trial for a dengue vaccine candidate, with plans to begin regulatory filings in many countries that are endemic for dengue infection, as well as the U.S. and Europe, in 2021. Subject to regulatory approval, we will work with governments, multilateral development banks and other partners to maximize the availability of and access to the vaccine in the places of greatest need.
  
  
• COVID-19. The COVID-19 pandemic continues to affect communities around the world. To accelerate the availability of a COVID-19 vaccine, we are leveraging our extensive and well-established global manufacturing and supply capabilities, building upon Takeda’s existing support of influenza pandemic preparedness in Japan. Takeda is partnering with the Government of Japan and Novavax on the development, manufacturing and commercialization of NVX CoV2373, Novavax’s COVID-19 vaccine candidate, in Japan. Takeda also entered into a three-way agreement with Japan’s Ministry of Health, Labour and Welfare (MHLW) and Moderna to import and supply Moderna’s COVID-19 vaccine candidate, mRNA-1273, in Japan.
  
  
• Zika. Around the world, 87 countries and territories have had evidence of Zika virus. Takeda is partnered with the U.S. government (Biomedical Advanced Research and Development Authority) to develop a Zika vaccine candidate that’s in Phase 1 development and was granted Fast Track designation by the U.S. Food and Drug Administration in 2018.
  
  
• Norovirus. Norovirus causes more than 685 million infections and an estimated 200,000 deaths each year. Our vaccine candidate has completed a Phase 2b field efficacy trial, and we’re encouraged by the results, which we consider a proof of concept for the vaccine. This data was published in Vaccine in September 2020.