Tissue Factor (TF), also known as coagulation factor III (CD142), is a transmembrane glycoprotein that serves as the principal initiator of the extrinsic coagulation pathway. While TF exhibits restricted expression in healthy perivascular tissues, it is aberrantly and frequently overexpressed in a broad spectrum of solid tumors, including cervical, pancreatic, head and neck, and lung cancers. This tumor-specific upregulation is associated with enhanced tumor progression, invasion, metastasis, and angiogenesis, making TF a compelling therapeutic target for antibody-drug conjugate (ADC) development. ADCs targeting TF are designed to selectively deliver cytotoxic payloads to tumor cells while minimizing harm to normal tissue, thus offering a promising approach to address the limitations of conventional therapies for TF-expressing malignancies. [1][2]
Adcendo, a clinical-stage biotechnology company, is advancing a pipeline of next-generation ADCs targeting high unmet medical needs in oncology, with a particular focus on TF and other tumor-associated antigens. The company has announced substantial progress across its pipeline, and in this article, we review recent clinical and regulatory milestones for Adcendo’s leading ADC candidates, including pivotal clinical trial results and regulatory designations.ADCE-T02: Clinical Progress in Advanced Solid Tumors
ADCE-T02 is a potential best-in-class antibody-drug conjugate (ADC) targeting Tissue Factor (TF), a clinically validated antigen overexpressed in a range of solid tumors, including head and neck squamous cell carcinoma (HNSCC), pancreatic ductal adenocarcinoma, non-small cell lung cancer, and colorectal cancer. The agent is currently being evaluated as monotherapy in the ongoing Tiffany-01 Phase I clinical trial (NCT06597721) enrolling patients with advanced solid tumors. The study has progressed to the cohort expansion phase, in which two go-forward dose levels are being evaluated in a randomized setting to optimize dosing and further assess safety, anti-tumor efficacy, and durability of response.[3]
ADCE-T02 consists of a humanized anti-TF monoclonal antibody specifically engineered to minimize impact on coagulation, conjugated via a hydrophilic, cleavable T1000 linker to an exatecan (topoisomerase I inhibitor) payload at a drug-to-antibody ratio of approximately 4. This design aims to maximize anti-tumor activity while reducing off-target toxicities.
Preclinical data supporting the clinical development of ADCE-T02 were recently highlighted at the annual meeting of the American Association for Cancer Research (AACR) held April 17-22, 2026, in San Diego, CA, and published in Molecular Cancer Therapeutics.[3][4]
In HNSCC models, ADCE-T02 demonstrated robust anti-tumor activity, including efficacy in models resistant to epidermal growth factor receptor (EGFR)-targeted therapies, and induced marked tumor regression in large and treatment-refractory xenografts. Toxicology studies in non-human primates indicated a favorable safety profile, with no evidence of ocular, skin, lung, or peripheral nerve toxicity. Collectively, these findings suggest that ADCE-T02 may provide a superior therapeutic window compared with current TF-targeted ADCs.
ADCE-D01: Regulatory Milestones and Clinical Evaluation in Mesenchymal Malignancies
ADCE-D01 is a first-in-class ADC targeting urokinase plasminogen activator receptor-associated protein (uPARAP, endo180, CD280) an endocytic receptor highly overexpressed in mesenchymal tumors. The investigational agent is composed of a humanized anti-uPARAP IgG1 monoclonal antibody conjugated via a GFGG tetra-peptide linker moiety to the Topoisomerase I inhibitor P-1021 payload at a drug-to-antibody ratio (DAR) of 8.
High expression levels of uPARAP are generally found on malignant cells of various non-epithelial cancers such as soft tissue sarcoma (STS) and osteosarcoma, glioblastoma multiforme and mesothelioma. The highly prevalent expression in non-epithelial tumors makes ADCE-D01 a very attractive target for and ADC for the treatment of sarcomas.[5]
ADCE-D01 has recently been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of soft tissue sarcoma, following Fast Track Designation received in October 2025.
The agent leverages a uPARAP-binding antibody conjugated to a topoisomerase I inhibitor via a protease-cleavable linker, facilitating selective tumor targeting based on uPARAP’s rapid internalization and low expression in healthy tissues. ADCE-D01 is being evaluated in the ADCElerate1 Phase 1/2 (NCT06797999), an open-label, multicenter dose-escalation and expansion study in patients with metastatic or unresectable soft tissue sarcoma across the US and Europe. Key objectives include evaluation of safety, tolerability, pharmacokinetics, and preliminary anti-tumor efficacy.
Preclinical studies have demonstrated potent anti-tumor effects in multiple mesenchymal tumor models, along with a favorable toxicology profile.
ADCE-B05: Early Clinical Evaluation in Squamous Cell Tumors
ADCE-B05 is a first-in-class ADC directed against a novel, with a yet undisclosed target that is highly expressed in squamous cell tumors. The first-in-human Phase 1 clinical trial (NCT07362888) has enrolled its initial patient, with sites in the US and Australia. The study will assess safety, tolerability, and optimal dose selection, including the Maximum Tolerated Dose (MTD) and the Recommended Expansion Dose (RED) in advanced squamous cell malignancies.
Preclinical investigations have demonstrated robust anti-tumor activity and encouraging tolerability for ADCE-B05 in squamous cell cancer models, providing the rationale for clinical evaluation.
Outlook
Adcendo’s ADC pipeline continues to advance with three separate Phase 1 studies actively enrolling patients with high unmet need cancers. Supported by recent financing, the company aims to accelerate clinical development and deliver novel treatment options for cancer patients with limited therapeutic alternatives.
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Clinical trials
ADCE-T02, a Tissue Factor Targeted Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours
ClinicalTrials.gov ID NCT06597721
First-in-Human Study of ADCE-D01 in Soft Tissue Sarcoma (ADCElerate1) – ClinicalTrials.gov ID NCT06797999
First-in-Human Study of ADCE-B05 in Patients With Advanced Solid Tumors – ClinicalTrials.gov ID NCT07362888
Highlights of Prescription Information
References
[1] Kasthuri RS, Taubman MB, Mackman N. Role of tissue factor in cancer. J Clin Oncol. 2009 Oct 10;27(29):4834-8. doi: 10.1200/JCO.2009.22.6324. Epub 2009 Sep 8. PMID: 19738116; PMCID: PMC2764391.
[2] Li X, Cao D, Zheng X, Wang G, Liu M. Tissue factor as a new target for tumor therapy-killing two birds with one stone: a narrative review. Ann Transl Med. 2022 Nov;10(22):1250. doi: 10.21037/atm-22-5067. PMID: 36544632; PMCID: PMC9761121.
[3] Poulsen TT, Ilina O, Barkholt P, Pontieri D, Bomholt Lange J, Wardman JH, Côme C, Hjæresen C, Liu SH, Meng X, Zhang Y, Mumberg D. A clinical stage antibody drug conjugate targeting tissue factor demonstrates strong efficacy in preclinical models of head and neck squamous cell carcinoma. In: Proceedings of the 117th Annual Meeting of the American Association for Cancer Research; 2026 April 17-22; San Diego, CA.: AACR; 2026. Abstract nr 6927 / 8
[4] Poulsen TT, Ilina O, Wardman JH, Bie A, Bornholdt J, Gillberg M, Pontieri D, Barkholt P, Côme C, Zhang Y, Zhang J, Wang Y, Shi H, Liu SH, Meng X, Mumberg D. ADCE-T02 – a Next Generation Antibody Drug Conjugate Targeting Tissue Factor Demonstrates Superior Preclinical Efficacy and Tolerability. Mol Cancer Ther. 2026 Apr 17. doi: 10.1158/1535-7163.MCT-26-0045. Epub ahead of print. PMID: 41996633.
[5] Wardman JH, Bie A, Come C, Barkholt P, Van Putten S, Løkke C, Gregersen I, Lange J, Gillberg M, Krogh-Madsen M, Bannister K, Poulsen TT, Nielsen C,Engelholm L, Behrendt N, Lynch C, Hemmingsen P, Mumberg D. ADCE-D01: a first in class antibody drug conjugate against urokinase plasminogen activator receptor-associated protein (uPARAP) demonstrates excellent preclinical efficacy and tolerability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4784.
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