Tissue factor tempts Adcendo
Tissue factor, best known for its role in blood clotting, has also yielded an approved cancer therapy in Pfizer and Genmab’s Tivdak – and today Adcendo decided that it wanted in on this target. The private Danish group has licensed the TF-targeting antibody-drug conjugate ADCE-T02 from Multitude Therapeutics outside China; the undisclosed up-front fee is presumably small despite the deal’s $1bn biodollar value. The rest of the TF space looks sparse beyond Tivdak, suggesting a lack of enthusiasm for the target, but Adcendo sees its new asset as differentiated: while Tivdak and the other main clinical-stage candidate, Lepu’s MRG004A, use auristatin payloads, ADCE-T02 employs an in-vogue topoisomerase 1 inhibitor, and its design is said to minimise impact on the coagulation pathway. Tivdak has a warning on its label for haemorrhage. ADCE-T02 will soon be put to the test, with a phase 1 study set to start in Australia later this year, and a US IND planned “in the near future”. Other topoisomerase-based projects aren’t too far behind, though – including one from Exelixis, which earlier this month discontinued its first-generation TF-targeting ADC, XB002, citing undifferentiated early clinical data. XB002, which was licensed from Iconic Therapeutics, employed an auristatin payload.
Tissue factor-targeting ADCs in development
Project | Company | ADC details | Status |
---|---|---|---|
Tivdak (tisotumab vedotin) | Pfizer (via Seagen)/Genmab | Auristatin payload; DAR 4.1 | Approved for 2nd-line cervical cancer |
MRG004A | Lepu Biopharma | Auristatin payload; DAR 3.8 | Ph1/2 data in solid tumours presented at ASCO 2024 |
XNW28012 | Evopoint Biosciences | None given | Ph1/2 Chinese trial in solid tumours |
ADCE-T02 | Adcendo/Multitude Therapeutics | Topoisomerase 1 inhibitor payload | Preclinical; ph1 to start in Australia Q4 2024 |
STRO-004 | Sutro Biopharma | Topoisomerase 1 inhibitor payload; DAR 4 | Preclinical; IND due 2025 |
XB371 | Exelixis | Topoisomerase 1 inhibitor payload; DAR 8 | Preclinical; IND due 2025 |
HRA00184-C004 | Jiangsu HengRui | Topoisomerase 1 inhibitor payload | Preclinical data at AACR 2024 |
BYON11852 | Byondis | None given | Preclinical |
Note: DAR=drug-antibody ratio. Source: OncologyPipeline.
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