HERA-GITRL Shows Strong Single-Agent Anti-Tumor Activity in Vitro and in Vivo and is Superior to Bivalent Clinical Benchmark Antibody
Heidelberg, Germany, July 23, 2019
Apogenix, a biopharmaceutical company developing nextgeneration immuno-oncology therapeutics, announced today thatnew data published in Journal for ImmunoTherapy of Cancer demonstrate the potent anti-tumorefficacy of Apogenix’ HERA-GITRL. HERA-GITRL is a hexavalent GITR receptor agonist that acts directly on immune cells, thereby enhancing their anti-tumor immunity. GITR is an especially important target for immunotherapy as GITR signaling provides co-stimulatory signals to boost T cell activation, differentiation, survival, and memory formation.
The strong single-agent anti-tumor activity of HERA-GITRL was demonstrated in two different cancer models. Treatment with HERA-GITRL resulted in dose-dependent tumor growth inhibition and increased T cell infiltration in the tumor. Further, it significantly boosted proliferation and differentiation of stimulated T cells while not producing any response in unstimulated T cells. In contrast to antibodies, HERA-GITRL does not depend on Fcγ receptor-mediated crosslinking for activity. In a direct in vitrocomparison with a clinical benchmark anti-GITR antibody, only HERA-GITRL achieved full biological activity independent of additionalcrosslinking. Interestingly, while HERA-GITRL consistently increased T cell activity, the clinical benchmark anti-GITR antibody consistently reduced T cell activity.
In line with previously published findings with HERA-TRAIL, HERA-CD40L, and HERA-CD27L, the HERA-GITRL manuscript data show that optimal stimulation of tumor necrosis factor superfamily receptors can be achievedwith the hexavalent structure of HERA-GITRL, which mimics the natural ligand. In contrast, bivalent compounds, such as antibodies, appear to beunsuitable for stimulating the TNF receptor superfamily due to fundamental structural and functional characteristics, including only two target-binding domains.
“We have developed HERA-GITRL, apotent GITR receptor agonist, to overcome the shortcomings of antibody-based approaches,” said Thomas Hoeger, Ph.D., Chief ExecutiveOfficer of Apogenix.
“While our HERA-ligands work well as stand-alone therapies, we are also assessing the synergies with traditional cancer therapies as well as other immuno-oncology therapeutics. HERA-GITRL and our other HERA-ligands have the ability to boost T cell priming and will therefore work well in combination with immune checkpoint inhibitors which depend on the presence of previously primed anti-tumor T cells. We look forward to advancing our HERA-ligands to the clinical stage.”