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AK146D1 is Akeso's Nectin-4 × TROP2 bispecific ADC, combining the two most validated ADC addresses in one molecule.
AK146D1 is Akeso's bispecific antibody-drug conjugate that binds both Nectin-4 and TROP2, the two most clinically validated ADC targets, and delivers a topoisomerase I inhibitor through a cleavable linker. The rationale is complementary expression across urothelial, breast and lung cancers and potentially higher internalisation when two receptors are engaged on the same cell. It entered the clinic in 2025 in a first-in-human phase 1 dose-escalation study after IND clearance in China, alongside Avenzo's AVZO-103 in the same target pair. No efficacy or toxicity data have yet been reported, so the programme is very early. Whether dual targeting improves on single-target ADCs such as enfortumab vedotin and sacituzumab govitecan, or simply adds toxicity, is the central question. For a newcomer: it combines two proven ADC addresses in one molecule, and the clinic has yet to show if that helps.
AK146D1 carries a camptothecin-derived TOP1 inhibitor; exatecan shown as the class representative.
Bispecific Nectin-4/TROP2 antibody with TOP1 payload. Connects to Nectin-4 and TROP2.
1.Antibody binds Nectin-4 and TROP2 (bispecific) on the tumour cell surface
Source: clinicaltrials.gov. Doses are for orientation; the current label governs.
IND cleared; first-in-human phase 1 started source
| Country | Reimbursement | List price | Assistance |
|---|---|---|---|
| China | Investigational | not disclosed | - |
List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.
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Query for this drug: (TITLE:"AK146D1" OR ABSTRACT:"AK146D1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about AK146D1, not a curated reading list.
Shares Exatecan (and derivatives), Topoisomerase-I inhibitor payloads, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs, Bispecific ADC.
Shares Exatecan (and derivatives), Topoisomerase-I inhibitor payloads, Triple-negative breast cancer (TNBC).
Shares TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET, TROP2, Triple-negative breast cancer (TNBC), Non-small-cell lung cancer.
Shares Exatecan (and derivatives), Topoisomerase-I inhibitor payloads, TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs.
Shares TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs, TROP2, Triple-negative breast cancer (TNBC).
Shares ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs, Bispecific ADC, Triple-negative breast cancer (TNBC).
Shares Nectin-4, Bispecific ADC, TROP2.