Denmark’s Adcendo, a biotech company focused on the development of breakthrough antibody-drug conjugates (ADCs) for the treatment of underserved cancers, has signed a licensing agreement with Duality Biologics, a clinical-stage biotech company focused on discovering and developing a pipeline of ADCs targeting cancers and autoimmune diseases.

Under the terms of the agreement, Adcendo will license Duality Biologics’ proprietary DITAC (Duality Immune Toxin Antibody Conjugates) linker/payload technology platform for its lead uPARAP-ADC program in mesenchymal cancers. The DITAC platform is designed to generate ADCs with superior safety profiles, sustainable payload delivery and release in tumors, and efficient bystander killing of antigen low and negative cells.

Both parties are in discussions to expand the license agreement to cover additional targets selected by Adcendo.

uPARAP
The urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180), a recycling endocytic receptor involved in collagen homeostasis and turnover, is a novel cancer target over-expressed on the cell surface of malignant cells in several non-epithelial cancers, including soft-tissue sarcoma and osteosarcoma, glioblastomas and subsets of acute myeloid leukemia. In contrast, in healthy adult individuals, expression is restricted to minor subsets of mesenchymal cells. [1][2]

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uPARAP is one of the four members of the mannose receptor family along with a macrophage mannose receptor (MMR), a phospholipase lipase receptor (PLA2R), and a dendritic receptor (DEC-205 also known as CD205). As a clathrin-dependent endocytic receptor for collagen or large collagen fragments as well as through its association with urokinase (uPA) and its receptor (uPAR), uPARAP takes part in extracellular matrix (ECM) remodeling, cell chemotaxis and migration under physiological (tissue homeostasis and repair) and pathological (fibrosis, cancer) conditions.[1]

ADC Target
Functionally, uPARAP/Endo180 is a rapidly recycling endocytic receptor that delivers its cargo directly into the endosomal-lysosomal system. This opens a potential route of entry into receptor-positive cells.

This combination of specific expression, endocytic function and the unique internalization properties of uPARAP make it a highly attractive ADC target.

“We are very pleased to announce this agreement to leverage Duality’s DITAC platform for our first-in-class uPARAP ADC program,” said Michael Pehl, Chief Executive Officer of Adcendo.

“We believe that Duality, through its DITAC platform, has clearly brought linker-payload technologies to the next level and we are very much looking forward to collaborating closely and developing ADCs with a superior safety and efficacy profile for cancer patients in need,” Pehl added.

Next-generation ADC-company
“Duality is dedicated to becoming a leading next-generation ADC company. The clinical assets built upon our DITAC platform have started to show encouraging efficacy and safety results in patients,” noted John Zhu, Chief Executive Officer of Duality.

“We are very glad to work with Adcendo on breakthrough ADC medicines and apply our platform to its novel and unique uPARAP program. We believe the collaboration reflects the mutual recognition of each party’s unique strengths in ADC discovery and development and look forward to supporting the development of innovative ADC drugs,” concluded Zhu.

Reference
[1] Gucciardo F, Pirson S, Baudin L, Lebeau A, Noël A. uPARAP/Endo180: a multifaceted protein of mesenchymal cells. Cell Mol Life Sci. 2022 Apr 22;79(5):255. doi: 10.1007/s00018-022-04249-7. PMID: 35460056; PMCID: PMC9033714.
[2] Nielsen CF, van Putten SM, Lund IK, Melander MC, Nørregaard KS, Jürgensen HJ, Reckzeh K, Christensen KR, Ingvarsen SZ, Gårdsvoll H, Jensen KE, Hamerlik P, Engelholm LH, Behrendt N. The collagen receptor uPARAP/Endo180 as a novel target for antibody-drug conjugate mediated treatment of mesenchymal and leukemic cancers. Oncotarget. 2017 Jul 4;8(27):44605-44624. doi: 10.18632/oncotarget.17883. PMID: 28574834; PMCID: PMC5546505.

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