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When Marie Evangelista and her colleagues pitched their KRAS plan, others on Genentech’s R&D team were skeptical. Evangelista wanted to pan for conformationally selective antibodies that could lock KRAS into an inactive form, in the hopes that these antibody tools could be used to screen for and characterize small-molecule KRAS contenders. But, management pushed back, would it be possible to find antibodies with the right conformational selectivity? “Everybody gave it a thumbs down. Nobody thought it was going to work,” says Evangelista.