HONG KONG – Takeda Pharmaceuticals Inc. is gaining access to the “library of libraries,” inking an agreement with Twist Bioscience Corp. in one of the Osaka, Japan-based firm’s recent efforts to build a sustained innovative R&D growth engine.

The past few years has seen Takeda complete its $62 billion acquisition of rare disease specialist Shire plc and, more recently, its divestitures of noncore assets, with a pledge to focus on next-generation therapies involving a range of modalities.

“Takeda’s research engine is investing in next-generation technologies beyond small molecules to bring a new wave of innovative treatments to patients,” said Robert Mabry, Takeda’s global head of biologics research. “With our biologics discovery capabilities, we’re pursuing approaches that go beyond traditional monoclonal antibodies.”

The recent agreement with Twist will give Takeda access to phage display libraries and help develop new antibody candidates. Twist Bioscience subsidiary Twist Biopharma is licensing its “library of libraries,” which consists of a panel of synthetic antibody phage display libraries, which in turn are derived from sequences that exist in the human body. The two companies will use that resource to discover, validate and optimize new candidates in the oncology, rare diseases, neuroscience and gastroenterology fields.

“Twist’s ability to generate robust, diverse and cutting-edge libraries through its proprietary silicon platform, together with our deep insight into therapeutic drug discovery and development, will help us expand a growing pipeline of targeted biologic candidates,” Mabry told BioWorld. “Our collaboration with Twist provides access to both off-the-shelf phage libraries and custom libraries, in multiple formats. This technology can help Takeda accelerate the discovery and development of novel biologics across our core therapeutic areas.”

When asked how access to the library would drive the collaboration with Takeda, Emily Leproust, Twist Bioscience CEO and co-founder, said, “There is a greater likelihood of finding high-affinity binding antibodies that can subsequently be optimized for specific therapeutic properties.”

According to Leproust, “Takeda will pay Twist annual technology licensing fees, as well as milestones and royalties for all antibodies discovered from the Twist phage display libraries,” though she declined to provide specific financial details. She also said that alongside its financial aspects, the partnership is an opportunity for the two companies to work together to drive drug discovery. 

The libraries within Twist’s “library of libraries” are made up of different antibody fragment scaffolds such as scFv, VHH and Fab, alongside different sources of human antibody repertories. Some of the libraries are focused on particular classes of difficult-to-drug targets such as G protein-coupled receptors (GPCRs), ion channels and carbohydrates. Each library has more than 10 billion antibodies, with the library of libraries’ diversity dramatically increased as the number of total libraries increase, Leproust said.

Twist is currently working with “a variety of companies through its biopharma division” to increase access to that library resource. Alongside the Takeda partnership, Twist has also announced collaborations with autoimmune-focused Pandion Therapeutics Inc., contract research and manufacturing firm Lakepharma Inc. and animal health company Invetx Inc. “Each relationship is unique in the scope, but all are focused on drug discovery and/or optimization using the proprietary Twist methods to build precise libraries,” said Leproust. Twist expects to announce more collaborations in 2020.

Leproust told BioWorld COVID-19 has had no impact on the partnership process. Twist, however, is currently developing competitive antibodies against both the spike protein on COVID-19 and the ACE2 receptor in human cells, with a next step of tests for neutralization against the live virus. A GLP1R antagonist for potential treatment of congenital hyperinsulinism has demonstrated efficacy during preclinical trials.

Twist joined an international alliance led by Singapore’s Proteona Pte. Ltd. to develop broadly neutralizing antibodies against coronaviruses, including COVID-19, on June 1. Announced on March 25, the alliance’s other founding members include Heidelberg University Hospital, Tübingen University Hospital, the German Cancer Research Center, the NMI Natural and Medical Sciences Institute, NUS Enterprise, U.S.-based 10x Genomics and NovogeneAIT.

Meanwhile, Takeda is advancing its own efforts against COVID-19, having established the CoVIg-19 Plasma Alliance, a plasma industry collaboration to develop a plasma-derived hyperimmune globulin therapy for COVID-19, in March. The alliance now boasts 10 global plasma companies, as well as global organizations not in the plasma industry, who are encouraging more plasma donations.

Late last year, Takeda disclosed plans for ramping up its R&D pipeline, which it said includes 12 new molecular entities, and the potential for 14 launches through the 2024 fiscal year.

Takeda is also awaiting approval for the sale of its Asia-Pacific primary care portfolio to Celltrion Inc.’s Singaporean arm on June 11. The sale saw Takeda earn an initial $266 million in cash and an additional $12 in milestone payments. The company also completed a sale of noncore assets spanning the Russia-CIS region for $660 million, and in countries across the Near East, Middle East and Africa region for $200 million in March 2020. Included in the sales were German companies Acino Holding AG and Stada Arzneimittel AG.

Those sales helped the company reach 80% of its goal of divesting ¥1 trillion (US$93.2 billion) worth of assets after its acquisition of Shire closed in January 2019.

Takeda declined to comment on the prospect of future divestments, but Mabry added, “Divestment announcements are a step in Takeda’s effort to simplify our portfolio, accelerate deleveraging, and continue to invest in our core products.”

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