OMP-305B83 (Anti-DLL4/VEGF Bispecific Antibody)

Proposed Mechanism of Action

OMP-305B83 is a bispecific antibody targeting Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF).

DLL4 is one of the ligands of the Notch receptor.1,2 Notch plays a role in the development of stem cells, and aberrant Notch signaling has been associated with tumorigenesis and chemoresistance in a variety of tumors.2,3

VEGF is an inducer of angiogenesis and can contribute to tumorigenesis.4 Binding of VEGF to its receptor can activate pathways involved in survival, proliferation, differentiation, and migration.5


DLL4, Delta-like ligand 4; CSC, cancer stem cell; IL-17, interleukin-17; MDSC, myeloid-derived suppressor cell; DC, dendritic cell.

OMP-305B83 by Disease State

OMP-305B83 in Solid Tumors

OMP-305B83 in Solid Tumors

Preclinical studies have shown that targeting Notch signaling and VEGF pathways inhibits tumor growth and reduces cancer stem cell frequency.6,7 Studies in xenograft models of human tumors demonstrated that simultaneous inhibition of DLL4 and VEGF demonstrated antitumor activity, ability to delay tumor recurrence, and reduction of stem cell frequency.8

OMP-305B83 is an anti-DLL/VEGF bispecific antibody currently owned by OncoMed.

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

References

  1. Hori K, et al. J Cell Sci. 2013;126(pt 10):2135-2140.
  2. Ntziachristos P, et al. Cancer Cell. 2014;25(3):318-334.
  3. Güngör CI, et al. Br J Pharmacol. 2014;171(4):849-858.
  4. Goel HL, Mercurio AM. Nat Rev Cancer. 2013;13:871-882.
  5. Roberts E, et al. Prostate Cancer. 2013;2013:418340.
  6. Hoey T, et al. Cell Stem Cell. 2009;5:168-177.
  7. Beck B, et al. Nature. 2011;478:399-403.
  8. Yen W. AACR 2014 [abstract 207].