MacroGenics has made the final decision to abandon work on one of its more advanced antibody-drug conjugates after taking a look at the latest phase 2 data.
The biotech had already paused work on vobramitamab duocarmazine (vobra duo) back in November, explaining that it was awaiting progression-free survival (PFS) data from a phase 2 monotherapy prostate cancer trial. Vobra duo has a cleavable peptide linker designed to deliver a DNA-alkylating duocarmycin payload to solid tumors that express B7-H3.
CEO Scott Koenig, M.D., Ph.D., explained to investors at the time that the company would make a call on whether to invest further in vobra duo after considering the final PFS data, the therapy’s safety profile and the competitive landscape in the context of the rest of its pipeline.
The results are now in, and they show a median radiographic PFS of 9.5 months and 10 months for the 2-mg/kg and 2.7-mg/kg doses, respectively. Safety data “remained consistent with prior data disclosures,” MacroGenics said in its full-year earnings results March 20.
“Based on its assessment of the vobra duo safety and efficacy profile and an internal resource and portfolio review, MacroGenics has decided not to pursue further internal development of vobra duo and will instead explore potential alternatives for partnering this program,” the company said in the release.
Despite giving up on vobra duo, Koenig said the company still believes B7-H3 has “potential” as a target, adding that the biotech is “pleased with the progress being made with our alternate anti-B7-H3 ADC, MGC026.”
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MacroGenics pauses work on vobra duo ADC pending mature survival data
MGC026, which is a TOP1i-based ADC, is undergoing a phase 1 dose-escalation study in patients with advanced solid tumors. The biotech also has another ADC in the clinic in the form of MGC028, a TOP1i-based ADC that targets ADAM9 and recently started a phase 1 study in solid tumors.
MacroGenics is awaiting a readout later this year for lorigerlimab, a PD-1xCTLA-4 bispecific that the company is testing in a phase 2 prostate cancer trial in combination with docetaxel.
“We concluded 2024 with the achievement of multiple clinical development milestones, including the completion of enrollment in the LORIKEET phase 2 study evaluating lorigerlimab in combination with docetaxel in patients with mCRPC,” Koenig said in yesterday's postmarket release.
“We look forward to building upon this momentum in 2025 as we work to advance our novel pipeline of clinical product candidates, including lorigerlimab, MGC026 and MGC028,” the CEO added.
MacroGenics entered the year with $201.7 million in the bank, which the company expects to last into the second half of 2026.