AstraZeneca’s drug portfolio already includes a lymphoma drug, a blockbuster seller that treats cancer by going after a single target. Cancer drug research is expanding to therapies that address multiple targets, and AstraZeneca is now joining in by buying TeneoTwo, a biotech with a Phase 1 drug candidate that hits two targets simultaneously.

The pharmaceutical giant announced Tuesday that it has agreed to pay $100 million up front to acquire TeneoTwo. Phase 1 testing of the biotech’s drug, TNB-486, is underway in advanced B-cell non-Hodgkin lymphoma. If the drug achieves development and commercialization milestones, TeneoTwo shareholders could receive up to $1.16 billion in milestone payments.

TeneoTwo’s drug is part of a class of therapies called T cell engagers. These drugs address two targets, one on a cancer cell and the other on a T cell. By engaging both simultaneously, these therapies are intended direct a T cell to kill the targeted cancer cell. Amgen’s Blincyto pioneered this approach in the treatment of several types of leukemia. But that drug still poses serious side effect risks and companies developing new T cell engagers are all trying to improve the safety and efficacy of this drug class. They’re also trying to expand these cancer therapies to solid tumors. Amgen is one of these companies.

Last year, Amgen paid $900 million up front to acquire Teneobio, a company developing bispecific T cell engagers. These drugs target the protein CD3 on T cell as well as an antigen on cancer cells. Teneobio also brought to Amgen technology for developing antibody drugs capable of addressing multiple targets.
TeneoTwo, a subsidiary of Teneobio, designed TNB-486 to target CD19 on cancerous B cells and CD3 on T cells.

When Amgen announced the Teneobio buyout nearly a year ago, the drugmaker said it would spin out three of the biotech’s subsidiaries before closing the acquisition. Ancora Biotech, a Newark, California-based company formed last year by former Teneobio shareholders and executives, took over TeneoTwo along with the two other subsidiaries, TeneoFour and TeneoTen. TeneoOne, which was developing a bispecific antibody drug for multiple myeloma, was acquired earlier in 2021 by AbbVie.

In the announcement of the TeneoTwo acquisition, Anas Younes, AstraZeneca’s senior vice president of hematology R&D, said that the biotech’s drug candidate has potential as a monotherapy or as part of a combination treatment with a drug that targets CD20 on B cells.

“We believe this innovative molecule, which was designed to optimize the therapeutic window of T-cell activation, will enable us to explore novel combinations that have the potential to become new standards of care in this setting,” he said.

The TeneoTwo acquisition is just the latest in a series big pharma acquisitions of T cell engagers. Late last year, Sanofi agreed to pay $1 billion up front to acquire Amunix Pharmaceuticals, a clinical-stage company with technology that improves the safety and durability of these therapies. That deal followed Bristol Myers Squibb’s acquisition of global rights to the lead T cell-engaging drug candidate from Inmatics. Takeda Pharmaceutical joined the pursuit of new T cell engagers with the $525 million buyout of its clinical-stage partner, Maverick Therapeutics.

New startups are also emerging with technologies that enable a drug to hit multiple targets. Tentarix Bio emerged from stealth late last year with $50 million in funding to develop multi-specific drugs for cancer and autoimmune diseases. But some of the contenders have already hit setbacks. In March, Harpoon Therapeutics stopped work on its lead program following disappointing early-stage clinical data from a prostate cancer study.

AstraZeneca’s TeneoTwo acquisition is expected to close later in the current quarter. When it does, TeneoTwo’s drug will join an AstraZeneca cancer drug pipeline that includes Calquence, which has approvals in mantle cell lymphoma and chronic lymphocytic leukemia. The antibody drug, which blocks Bruton’s tyrosine kinase, an enzyme that regulates B cell growth, accounted for more than $1.2 billion in global sales last year. Clinical trials are underway that could expand use of the drug to earlier lines of cancer therapy.

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