VADC45 is composed of a human IgG1 antibody attached to the DGN549-C linker-payload, which has been used in two clinical-stage ADCs. VADC45 has been engineered to have a short half-life but highly specific to bind human CD45, which is expressed on normal hematopoietic stem and progenitor cells (HSPCs) and immune cells, including mature myeloid and lymphoid cells.
CD45 is an attractive target for conditioning of HSPCs and immune cells prior to hematopoietic cell transplant (HCT), with the potential to prevent allograft rejection and to improve outcomes with an improved safety and tolerability profile.
VADC has the potential to treat a number of diseases, including treatment of hematologic malignancies, as a targeted conditioning agent for gene therapies such as for sickle cell disease, holistic immune reset for autoimmune disorders, and for Vor Bio’s approach of combining this asset with epitope modification of CD45 to shield healthy stem cells.
We are progressing IND enabling studies to enable future Phase 1 studies.
ADCs targeting CD45, a transmembrane receptor found on hematopoietic stem and progenitor cells (HSPCs) and mature leukocytes, have been developed and evaluated for allogeneic HCT in mice. In mouse models, CD45-ADCs show efficacy in depletion of HSPCs, successful donor engraftment across MHC barriers, and a favourable toxicity profile.
Non-human primate models have been crucial for preclinical development of hematopoietic stem and progenitor cell (HSPC) therapies, since they share many properties with humans.
A CD45-targeted antibody-drug conjugate successfully conditions for allogeneic hematopoietic stem cell transplantation in mice.
