Therapeutic Pipeline
A Broad, Novel, and Competitive Pipeline Driven by INGENUITI Platform
DM919
Targeting NK and T Cells for Cancer Immunotherapy
DM919 is a humanized MICA/B-specific IgG1 monoclonal antibody designed to block the shedding of MICA and MICB proteins from cancer cells. Highly expressed in cancer cells, MICA/B are stress-induced ligands recognized by both innate and adaptive immune cells via NKG2D receptors. Through shedding MICA/B, tumor cells develop immune escape. DM919 restores and enhances NKG2D-dependent activation of NK and T cells in the TME, and therefore promotes anti-tumor activity in cancer patients.
D2M Biotherapeutics have shown that DM919 prevents MICA/B shedding, stabilizes surface MICA/B, presents shed MICA/B to activate NKG2D on NK or T cells, and enhances NK and T cells killing of tumor cells. In preclinical studies, DM919 has demonstrated significant antitumor activity as a single agent in a variety of tumor models. Furthermore, substantial synergistic anti-tumor effects have been demonstrated when DM919 is combined with anti-PD1 agent.
D2M is currently enrolling patients in a Phase 1/2 study of DM919 for the treatment of advanced solid tumors.
DM926
Reversing Broad Immune Suppression of Macrophages and T/NK Cells to Cancer
DM926 is a dual blocking antibody inhibiting both LILRB1 and LILRB2 receptors.
LILRB1 (ILT2) and LILRB2 (ILT4) are members of the same leukocyte Ig-like receptor (LILRBs, also known as ILTs, i.e., immunoglobulin-like transcripts) family. They co-express on myeloid cells such as macrophages (Mφ) and dendritic cells (DCs), acting as receptors for the immune suppressive ligand HLA-G. LILRB1 alone also expressed on T, B, and NK cells.
LILRB2 suppresses the stimulation immune response of myeloid cells, especially in the tumor microenvironment. LILRB1 mediates the inhibition of cytotoxicity in T and NK cells and preventing the efficient engulfment of tumor cells by macrophages.
By blocking both LILRB1 and LILRB2 simultaneously, DM926 aims to disrupt their interactions with their ligands, potentially offering an effective immunotherapy approach for cancer treatment. This dual-blocking antibody has the potential to overcome the shared or distinct roles of these receptors in broad immune suppression across myeloid cells and T/NK cells.
Our Leading Assets are Transforming Immunotherapy
But that’s only the beginning. Our INGENUITI platform powers new possibilities by leveraging human genetic data. Currently, we are actively pursuing over 10 discovery and preclinical programs through D2M’s internal research efforts and external collaborations.
