Approach
Opsyon develops effective antibody-based cancer therapies with reduced side effects and initial focus on Acute Myeloid Leukemia (AML). The technology has the potential to be translated and advanced for solid tumor therapies and a candidate molecule targeting pancreatic and ovarian cancer is under evaluation.
For better efficacy and less toxicity, Opsyon combines the advantages of cancer-specific antibodies with immune checkpoint inhibition in one drug and thus provides a highly specific tumor targeting, and most importantly, a local, tumor-restricted immune checkpoint inhibition.
The cancer-specific antibody (docking domain) binds cancer cells with high specificity, whereas the immune checkpoint inhibtion occurs via the so-called blocking domain consisting of SIRPα, the endogenous receptor of the CD47 immune checkpoint. CD47 is a marker of self and found on the surface of every cell in the human body. Upon binding to SIRPα, CD47 transmits a "don’t eat me signal" to immune cells, e.g. macrophages. Importantly, most cancer cells trick the immune system and upregulate CD47 to escape the recognition by the immune system and hence, the macrophage attack.
Indeed, blocking the CD47-SIRPα checkpoint has shown anti-cancer activity, also in AML, but is associated with toxicity due to the presence of CD47 on healthy cells. In contrast to other, more conventional CD47-targeting agents, Opsyon’s approach first detects and docks on cancer cells and then blocks CD47 locally, thereby activating the immune system. Healthy cells are spared and side effects are avoided.
Opsyon's approach: Fusing the endogenous, extracellular domain of SIRPα (low affinity to CD47 and weak binding to CD47-positive healthy cells) to an IgG1 tumor specific antibody (high affinity and strong binding to tumor cells) by a recombinant flexible linker to exploit multiple effector cells of the immune system to efficiently eliminate cancer cells. This technology combines three mode of actions:
- Phagocytosis (engulfment) by macrophages
- Killing by natural killer (NK) cells
- Long-lasting, tumor-antigen independent T-cell response
and is thus anticipated to be used as monotherapy, in lower concentration compared to anti-CD47 antibodies (no antigen sink effect) and has a low probability of CD47-related side effects.