AbbVie has cut short its call on the ADAM family. The ADAM9-targeted antibody-drug conjugate (ADC) IMGC936 fell short of safety and efficacy expectations in solid tumors, prompting AbbVie and its equal partner MacroGenics to walk away from the candidate.
MacroGenics worked with ImmunoGen, now part of AbbVie following a $10.1 billion deal, to advance the ADC to a phase 1 readout. ADAM9 is overexpressed in non-small cell lung, pancreatic, gastric, breast, ovarian and colorectal cancers, suggesting it could enable the safe delivery of cytotoxic payloads to tumor cells.
However, phase 1 data failed to make the case for further development of IMGC936. MacroGenics broke the news after the market closed Thursday, telling investors that neither it nor AbbVie plan to advance the molecule because it “did not achieve pre-established clinical safety and efficacy benchmarks.”
The statement lacks further information, but MacroGenics CEO Scott Koenig, M.D., Ph.D., discussed challenges facing the program on an earnings call in November, when he told investors that “identifying the appropriate dose” has always been one of the issues for IMGC936. At that time, ImmunoGen was still finishing up the lung cancer cohort, pushing back the readout from 2023 to 2024.
While the readout failed to support further development of IMGC936, MacroGenics continues to believe in the potential of ADAM9. The biotech has a second shot at the target, MGC028, that uses Synaffix’s linker-payload in preclinical testing.
MacroGenics plans to present preclinical data on MGC028 in April. Koenig teased the presentation on an earnings call Thursday, explaining that MGC028 had “specific dose-dependent in vivo antitumor activity” in ADAM9-positive models, including in gastric, lung, pancreatic, colorectal, and head and neck cancers.
For AbbVie, the retreat from IMGC936 eliminates a long-shot chance to realize additional value from the ImmunoGen takeover while leaving the core case for the deal intact. The takeover gave AbbVie control of the approved, FRα-directed ADC Elahere, which could generate blockbuster sales if it moves into earlier lines of therapy, and expertise in a modality that could support the Big Pharma’s solid tumor strategy.