Zymeworks follows Mersana

Mersana's long-overdue exit from NaPi2b blockade in 2023 saw several other biotechs continue trying to develop ADCs against this target, but one that won't for now go down this path is Zymeworks. During Wednesday's fourth-quarter investor presentation Zymeworks revealed that its competitor here, ZW220, was being "paused". ZW220 uses Zymeworks' novel topoisomerase 1 inhibitor payload, ZD06519, and had been expected to enter the clinic in mid-2025. Instead the company is prioritising another preclinical ADC that employs ZD06519, ZW251, which hits the higher-profile target GPC3. As for NaPi2b, Mersana had taken the most advanced ADC, upifitamab rilsodotin, all the way to phase 3 in ovarian cancer in the face of deteriorating mid-stage data, before finally throwing in the towel two years ago. That move left ZW220 as virtually the only remaining NaPi2b-targeting project in the industry pipeline, though MediLink and Tubulis later advanced contenders into clinical trials. Zymeworks still insists that ZW220 is differentiated, but says it won't take it forward owing to the need to prioritise the most promising assets. Evercore ISI's Jonathan Miller wrote that Zymework's pipeline was full either way, and that ZW220 was still ready to enter the clinic and available for partnering.

Industry projects* targeting NaPi2b

Note: *all ADCs, the only modality being employed against NaPi2b. Source: OncologyPipeline.