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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

ProjectCompanyADC detailsStatus
Tivdak (tisotumab vedotin)Pfizer (via Seagen)/GenmabAuristatin payload; DAR 4.1Approved for 2nd-line cervical cancer
MRG004ALepu BiopharmaAuristatin payload; DAR 3.8Ph1/2 data in solid tumours presented at ASCO 2024
XNW28012Evopoint BiosciencesNone givenPh1/2 Chinese trial in solid tumours
ADCE-T02Adcendo/Multitude TherapeuticsTopoisomerase 1 inhibitor payloadPreclinical; ph1 to start in Australia Q4 2024
STRO-004Sutro BiopharmaTopoisomerase 1 inhibitor payload; DAR 4Preclinical; IND due 2025
XB371ExelixisTopoisomerase 1 inhibitor payload; DAR 8Preclinical; IND due 2025
HRA00184-C004Jiangsu HengRuiTopoisomerase 1 inhibitor payloadPreclinical data at AACR 2024
BYON11852ByondisNone givenPreclinical

Note: DAR=drug-antibody ratio. Source: OncologyPipeline.