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This study builds upon pre-clinical and early-phase studies of KappaMab, a chimeric IgG1 mAb specific for KMA (3). Importantly, to date, KMA represents the only truly MM-specific mAb under clinical development. KMA is a tumour-specific cell surface antigen that is (unlike CD38, SLAMF7 or CD138) exclusively expressed on MM cells, including stem-like CD138-ve/CD45+ve populations. KappaMab binds to a unique conformational epitope on KMA which is presented on the myeloma cell membrane by kappa FLC (?FLC) that is not associated with immunoglobulin heavy chain. Furthermore, KappaMab shows a 5-fold higher avidity for membrane-bound KMA (IC50 2nM) over secreted kappa free light chains (FLC), consistent with no sink effect being demonstrable in the presently completed early phase clinical trials. In vitro studies show selective engagement of ADCC and antibody dependent cell phagocytosis by KappaMab on kappa-positive MM cells, moreover, LEN treatment upregulates KMA expression on MM cells promoting enhanced NK-mediated ADCC. This therefore provides a strong rationale for combining KappaMab with IMiDs, due to concurrent upregulation of the KMA target and effector cell cytotoxicity.

This study is for participants who have Von Willibrand Disease (VWD) and involves the use of a subcutaneous prophylactic treatment (HMB-002) to prevent and reduce the frequency and/or severity of bleeding events. The study is conducted in two parts. Part A: A single dose will be administered to determine the safety and tolerability of HMB-002 in participants with VWB. Part B: Three doses of HMB-002 will be given, one dose every four weeks, to determine safety and tolerability of the IP and capture information regarding any bleeding events experienced.

This is a Phase 1, multicenter, dose-escalation, and dose-expansion study to investigate the safety, tolerability, PK, PD, and preliminary clinical efficacy of INCA035784 in participants with MPN who are positive for CALR exon-9 mutation. This study will involve Q2W dosing with INCA035784. This IP is a T-cell redirecting bispecific antibody that selectively binds to the N-domain of the surface exposed mCALR and CD3 on T cells, designed to redirect CD3 T cells to recognize and eliminate mCALR-expressing malignant cells.