MacroGenics isn’t moving forward with an ADAM9-targeting antibody-drug conjugate (ADC) after lacklustre early data, and neither is partner AbbVie, who inherited the collaboration after its $10-billion acquisition of ImmunoGen.
However, Macrogenics isn’t giving up on the target; as part of its quarterly earnings Thursday, the company revealed an updated ADAM9 programme with a different cytotoxic payload.
MacroGenics originally partnered with ImmunoGen more than five years ago to equally share development of IMGC936, which delivers a maytansinoid payload, to treat various cancers. However, based on Phase I dose escalation and expansion data, the ADC didn’t reach pre-established safety and efficacy benchmarks.
In its earnings report, MacroGenics affirmed that ADAM9 “remains a promising target for delivery of an alternative cytotoxic payload” and unveiled MGC028, an ADC against ADAM9 that delivers a topoisomerase I inhibitor-based payload.
The company plans to present preclinical data for MGC028 at the American Association for Cancer Research (AACR) annual meeting in April. On a call with investors Thursday, CEO Scott Koenig gave a sneak-peek of the data, saying repeat dosing was well-tolerated in non-human primate toxicology studies. He added that the ADC “exhibited specific dose-dependent in vivo anti-tumour activity” in patient-derived cell and mouse models of cancers including gastric, lung, pancreatic, colorectal and head and neck cancers.
MacroGenics plans to submit a regulatory application with the FDA by year-end to begin clinical testing of MGC028. The company is also working on another topoisomerase I inhibitor-based ADC, dubbed MGC026, for which it recently began a Phase I study.