AbbVie Challenges Amgen With $100M Upfront for Trispecific Lung Cancer Drug

AbbVie's office in South San Francisco, California

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The Illinois-based pharma has committed more than $1 billion in milestones to secure rights to ZG006 and join a who’s who of drugmakers targeting the DLL3 protein.

AbbVie is paying $100 million upfront for ex-China rights to a potential challenger to Amgen’s lung cancer drug Imdelltra. The deal gives AbbVie access to ZG006, a DLL3xDLL3 T-cell engager that Suzhou Zelgen Biopharmaceuticals recently took into Phase III.

The pact, detailed in a Shanghai stock exchange filing first reported by Fierce Biotech, has AbbVie committing $1.075 billion in milestones to secure rights to ZG006. AbbVie will pay up to $60 million in near-term milestone payments based on clinical progress and fees related to licensing options, if it activates the China option.

ZG006 is operating in a popular space. Amgen is leading the pack after validating the concept of targeting DLL3 to treat small cell lung cancer (SCLC) with Imdelltra, a bispecific antibody that binds DLL3 on tumor cells and CD3 on T cells. Imdelltra received full FDA approval in extensive SCLC in November, after securing an accelerated nod in 2024.

ZG006, also known as alveltamig, is designed to improve on Imdelltra by binding to two distinct DLL3 epitopes on tumor cells and CD3 on T cells. The candidate’s trispecific T-cell engager design could drive efficacy against tumors with low DLL3 expression.

Zelgen, also known as Zejing Biopharmaceutical, reported Phase II data in SCLC last year. The biotech saw a 66.7% response rate in 27 heavily pretreated patients. All the patients had received at least two lines of therapy, with most previously taking an anti-PD-(L)1 checkpoint inhibitor. Nearly half the patients had received at least three lines of treatment.

Investigators retrospectively evaluated DLL3 expression, revealing that levels of the target were low in 21 of the participants. Zelgen reported a 71.4% response rate in an analysis that pooled the 21 patients with four participants who had medium DLL3 expression.

Imdelltra’s approval, meanwhile, was based on a Phase III trial that reported a 40% response rate in 99 SCLC patients who had tried at least two prior therapies.

Zelgen’s analysis included fewer patients, all of whom were enrolled in China. Responsibility for showing whether ZG006’s potential edge over Imdelltra holds up in larger global studies will fall to AbbVie, which joins many of its peers in the DLL3 space.

Merck, for instance, acquired the trispecific DLL3 T-cell engager MK-6070 when it bought Harpoon for $650 million in 2024. Daiichi Sankyo later paid Merck $170 million for a stake in the program.

Other Big Pharmas have irons in this fire as well. Boehringer Ingelheim has a bispecific DLL3xCD3 T-cell engager in Phase II. Roche has a Phase I trispecific antibody targeting DLL3 with bivalent CD3xCD137 binding. Targeting the costimulatory immunoreceptor CD137 is intended to increase efficacy.

Roche added a DLL3-directed antibody-drug conjugate to its pipeline in early 2025, also going to China to license a molecule in a $1 billion-plus biobucks deal.

Nick is a freelance writer who has been reporting on the global life sciences industry since 2008.
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