For the global pharmaceutical industry, 2024 was full of challenges. Nevertheless, Takeda delivered a strong performance, highlighted by breakthroughs in its R&D pipeline and its strategic collaborations, including the EU approval of its in-house developed rare disease drug Adzynma, and the Japan approval of Fruzaqla for the treatment of advanced or recurrent colorectal cancer that has progressed after chemotherapy. In 2023, Takeda reached a collaboration agreement with Hutchmed to obtain the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. Additionally, a novel treatment for narcolepsy type 1 developed within Takeda, oveporexton (TAK-861), also achieved promising data from its Phase 2B clinical trial.
Dr. Christopher Arendt
These achievements underscore Takeda's commitment to innovation through both internal R&D and collaborative efforts. In an exclusive interview, PharmaDJ sat down with Dr. Chris Arendt, Takeda's Chief Scientific Officer and Head of Research, to delve deeper into the company's approach to cultivating a diverse innovation ecosystem and its role in shaping the global pharmaceutical landscape.
Collaborative efforts for unmet needs
“When we are thinking about partnering or in-licensing, we look for molecules that are addressing unmet needs and that align with our three core therapeutic areas in oncology, neuroscience and gastrointestinal and inflammation,” Dr Arendt said. This strategy aligns with recent deals Takeda has done with the US biotech Keros Therapeutics and the Chinese biotech Ascentage.
Keros’ elritercept (TAK-226) is a novel activin inhibitor to treat anemia caused by certain blood cancers like myelodysplastic syndromes. In December 2024, Takeda entered into an exclusive licensing agreement with Keros to further develop, manufacture and commercialize elritercept. Takeda expects to submit the new drug application of elritercept to the FDA by 2029.
Ascentage’s olverembatinib, a third-generation BCR-ABL1 inhibitor, was approved in China in 2021 to treat chronic myeloid leukemia and is undergoing clinical studies in the US. Takeda has an exclusive option to commercialize olveremabatinb globally through an agreement signed in June 2024. While Takeda acquired the BCR-ABL1 inhibitor Iclusig (ponatinib) through the acquisition of Ariad in 2017, olverembatinib is a next-generation, potentially best-in-class asset.
“Takeda has an immense depth and breadth of expertise when it comes to hematological diseases. Ascentage provided us with an opportunity to reach broader patient populations who are burdened with cancers such as CML,” Dr. Arendt said.
Takeda's early-stage collaborations offer several exciting scientific opportunities. For instance, the drugmaker partnered with Degron, a China-based biotech company with operations in both China and the U.S., in May to discover molecular glue degraders to find solutions for oncology, neuroscience and gastrointestinal and inflammatory diseases.
“The Degron deal is an early-stage preclinical partnership that is about pushing the boundaries of innovation by targeting well validated biological targets through a cutting-edge new modality strategy,” Dr Arendt explained. He added that Takeda is interested in this space because molecular glues tend to be smaller molecules than PROTACs, which also induce protein degradation.
“In neuroscience, for example, we are looking for small molecules because of their size can be developed as oral medicines that are capable of traveling into the brain.”
In the areas of gastrointestinal and inflammatory diseases, Takeda is developing an oral allosteric TYK2 inhibitor zasocitinib (TAK-279), which was acquired from Nimbus Therapeutics in 2023. Takeda plans to initiate a Phase 3 study in psoriatic arthritis by the end of fiscal year 2024 and expects a Phase 3 study in psoriasis to read out in 2025.
An off-the-shelf approach to cell therapies
For Takeda, early-stage projects are also happening in advanced therapies like cell therapies. After deprioritzing three early-stage autologous CAR-T therapy assets in February, Takeda shifted its focus towards allogeneic, or off-the-shelf, cell therapies. In November, it partnered with Alloy Therapeutics to advance the development of allogeneic cell therapies using Takeda’s proprietary induced pluripotent stem cell (iPSC)-derived CAR-T and CAR-NK technologies to treat various solid and blood cancers.
“We opted to focus on innate-like immune cells such as natural killer cells and γδ T cells that can be brought forward in an allogenic treatment setting,” Dr. Arendt said.
Takeda demonstrated its ambition in allogeneic cell therapies in 2021 when it acquired London-based GammaDelta Therapeutics, which was developing a novel allogeneic γδ T cell platform. The following year, Takeda bought Adaptate Biotherapeutics, a GammaDelta spin-off developing biologics-based molecules known as γδ T cell engagers.
“The two purchases put Takeda in a leading position and gave us great strength in allogeneic cell therapies. These are differentiated cell therapies that we are interested in applying to broader diseases than cell therapies have been approved for so far,” he explained.
While acknowledging scientific risks are much higher in early-stage projects, Dr Arendt said that his team minimizes risk with close collaboration across its scientific teams and success-based milestones.
“We have the capabilities to do a lot of modeling and assessment work very early to ensure that we are selecting the best targets and modality approaches. When we identify something that is exciting to us, we commit to it,” he said.
The Unrivaled Speed and Quality of Chinese Innovation
Takeda started its business in China in 1994, and has seen significant advances in China’s pharma industry, especially in R&D. After three decades, Dr. Arendt said he is most impressed by China’s speed and quality of innovation.
“One of the extraordinary things about China that I think is unrivaled is the speed with which Chinese innovation is advancing,” he said. The builds of infrastructure, the seating of talent and the pace of advancement of R&D programs are truly extraordinary,” he said.
“Quality and speed are the two key factors to be successful in the industry and China is strong in both of them. So, I’d say ignore China at your peril,” he continued, adding that there used to be a perception that China was a country for me-too and me-better drugs. That is clearly no longer the case.
Indeed, Chinese biotechs have recently demonstrated growing innovation capabilities. According to McKinsey, these companies out-licensed over 70 assets globally between 2023 and the end of 2024 — more than double the amount from 2019 to 2020. Oncology assets have been leading this trend. The most recent example happened on Jan 13 during the J.P. Morgan Healthcare conference, where Abbvie signed an option license agreement with Simcere Zaiming to develop Zaiming’s SIM0500, a trispecific T cell engager for multiple myeloma that is currently in Phase I studies in China and the US.
To tap into China's innovation, Takeda’s Research organization is taking a two-pronged approach, actively seeking novel assets and innovative partners, like Degron, within the country while also trying to nurture innovations by working with local incubators, like its partnership with the Shanghai-based ATLATL in November 2024. As a well-known incubator, ATLATL also serves high-profile clients including Eli Lilly and Novo Nordisk. The collaboration will explore opportunities in early-stage development, new technology applications, the empowerment of innovative enterprises, talent nurturing and international exchange, for Takeda's areas of interest.
“The ATLATL partnership is really interesting, and I call it a gateway to an early innovation ecosystem,” Dr. Arendt said, adding that the partnership allows Takeda to access flexible labs, early Chinese innovators and support lab-based science.
“It’s a gateway for Takeda to get a better read on early innovation in China and to have a seat at the table when interesting science is happening there,” he said.
AI-powered decision making
Like many other big pharmas, Takeda deploys AI across its business departments. However, it is the data-intensive research area where AI holds the greatest potential - to assist in decision-making.
“Think about just the explosion of knowledge and data not only generated inside Takeda but also from our partners around the world. How to marry our data to external data and how
to integrate high-quality data into decision making represent huge opportunities,” Dr. Arendt pointed out. “Those decisions can occur at multiple levels during drug development processes.”
“Picking up a target, designing a molecule, finding a biomarker…thousands of decisions have to be made to succeed in delivering a new medicine to patients. If AI can allow us to make those decisions with higher effectiveness and rigor, it will greatly accelerate the process to timely bring an effective treatment to patients in need,” he continued.
While he acknowledges that there is a bit of hype around AI’s future capabilities, Dr. Arendt remains confident that the role of digital in accelerating R&D has great potential. For example, digital capabilities were used to facilitate the development of TAK-279.
“AI and other digital accelerators are being embedded in many of our drug development processes. It has huge potential in the industry,” he said.