
Lilly's dual Nectin-4 effort back on track

Lilly's unusual effort to develop two Nectin-4-directed ADCs simultaneously hit a bump in April when the phase 1 trial of one of these was suspended, but it now seems to be back on track. The Nexus-01 study of LY4052031, Lilly's in-house originated project, is now recruiting patients again, an updated clinicaltrials.gov listing reveals, having earlier been marked "suspended" for unspecified reasons. Nexus-01 started last year, just months after Lilly took into the clinic a separate anti-Nectin-4 ADC, LY4101174, which came via its 2023 acquisition of the private German biotech Emergence Therapeutics. With nothing publicly disclosed about the brief trial suspension it can only be guessed why LY4052031 has stumbled while LY4101174 hasn't; the molecules are broadly similar in design, their key divergence being the use of differing linkers. It's also yet to emerge whether and when Lilly will decide to prioritise one project over the other. For now the company remains responsible for two of the industry's 18 clinical-stage anti-Nectin-4 ADCs, according to OncologyPipeline.
Lilly's two anti-Nectin-4 ADCs
LY4101174 (ETx-22) | LY4052031 | |
---|---|---|
Originator | Emergence Therapeutics | Lilly |
MAb | Humanised, Fcγ-silent | Humanised, Fcγ-silent |
DAR | 8 | 8 |
Linker | Maleimide-ß-glucuronide PSAR (ex Mablink) | GGFG (ex ImmunoGen) |
Payload | Topo1i (exatecan) | Topo1i (LSN3889710) |
Phase 1 trial | Exceed, solid tumours | Nexus-01, solid tumours |
Phase 1 start | Mar 2024 | Jul 2024 |
Current status | Recruiting, ends 2027 | Recruiting after being suspended Apr-Aug 2025 |
Source: OncologyPipeline.
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