OPN-9627
Avoiding immune destruction
Target
Hit identification
Lead optimization
Preclinical
Phase 1
Phase 2
Target:
CD73
Therapeutic area:
GI cancers: gastric, liver,
pancreatic, and CRC
Value:
best-in-class potential;
orally available small molecule
Safety:
safety margin in dose range inding studies compared to effective doses for adenosine modulation in vivo
Next milestones:
IND enabling
go/no-go
CD73 inhibition prevents conversion of AMP to immuno-suppressive adenosine
Extracellular adenosine triphosphate (ATP) is an immune system “find me” signal that is present in certain tumor microenvironments. Extracellular adenosine conversely inhibits the antitumor immune response through binding to adenosine receptors (A2aR and A2bR) present on immune cells.
Many cancers utilize this anti-inflammatory adenosine pathway to avoid immune system detection by conversion of the “find me” ATP signal to the “hide me” adenosine signal. The nucleotidase CD73 is critical for the conversion of ATP to adenosine. Poor prognosis has been associated with high expression of CD73 in several tumor types, supporting the role of adenosine in the promotion of tumor growth.
Opna’s small molecule inhibitors target CD73, making the tumor
vulnerable to immune response.
Opna’s differentiated class of oral, small molecule inhibitors of CD73 block the adenosine pathway and exhibit an anti-tumor immune response synergistic with checkpoint inhibition. These compounds were created using structure-based drug design and they possess a unique CD73 binding mode and novel chemical core structure.
