Tricky mechanisms fall by the wayside
After Amgen terminated a phase 1 study of its MCL1 inhibitor tapotoclax for lack of clinical efficacy while declining to remove it from its pipeline, Gilead has taken more drastic action and discontinued its own contender, zamzetoclax. MCL1 is an antiapoptotic protein related to BCL-2, but unlike the latter it has few successes to its name, and clinical-stage discontinuations of MCL1 inhibitors include Prelude's PRT1419, AstraZeneca's AZD5991 and AbbVie's ABBV-467. News of the Gilead discontinuation came among second-quarter updates that also included a setback for ROR1 blockade, another disappointing mechanism, with Ipsen handing rights to the ADC STRO-003 back to its originator, Sutro. This came over a year after Ipsen and Sutro tied up in a deal worth $90m in "near-term payments", but in the meantime Ipsen hadn't even started a clinical trial, apparently putting down its decision to back out to "new data and developments in the ROR1 landscape", according to a Sutro statement. Meanwhile, alongside the discontinuation of zamzetoclax and the earlier disclosed handing back to Arcus of etrumadenant and quemliclustat, Gilead also canned its DGKα inhibitor GS-9911; Bayer and Incyte projects with this mechanism remain in play.
Selected recent discontinuations
| Project | Mechanism | Company | Note |
|---|---|---|---|
| Zamzetoclax (GS-9716) | MCL1 inhibitor | Gilead | Amgen’s tapotoclax (AMG 176) remains in development despite showing lack of efficacy in ph1 |
| IPN60290/ STRO-003 | ROR1 ADC | Ipsen handed rights back to Suto | Merck & Co’s zilovertamab vedotin has disappointed but remains in clinical development, as do several other ADCs |
| GS-9911 | DGKα inhibitor | Gilead | Bayer’s BAY 2862789 & Incyte’s INCB177054 (DGKα/ζ inhibitor) remain in clinical development |
Source: Q2 2025 earnings updates & OncologyPipeline.
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