HERA-4-1BBL / Apogenix - LARVOL DELTA

Investigational Combination of OX40 and 4-1BB Antibodies Shows Early Signs of Activity in Solid Tumors (Targeted Oncology) - P1 | N=87 | (NCT02315066) | Sponsor: Pfizer | "'In this first-in-human study of a novel immunomodulatory combination of the OX40 and 4-1BB agonistic antibodies ivuxolimab and utomilumab, the combination was generally associated with a tolerable safety profile in patients with advanced solid tumors enrolled in the dose-escalation and expansion cohorts, with no DLTs [dose-limiting toxicities] and mostly grade 1 to 2 treatment-related AEs [adverse events],' the study authors, led by Omid Hamid, MD, wrote in their report published in the Journal for ImmunoTherapy of Cancer."

P1 data

The novel hexavalent human CD137/4-1BB agonist HERA-CD137L promotes anti-cancer immunity by activating CD8 T cells while regulatory T cells are not affected (AACR 2018) - "In contrast, HERA-CD137L prevented Treg-mediated suppression of effector T cells. Based on the in vitro data presented, HERA-CD137L is a promising candidate to promote anti-tumor immune responses either as single agent or in combination with other IO-compounds."

IO Biomarker • Oncology

The novel hexavalent human GITR agonist HERA-GITRL promotes anti-tumor efficacy independent of Fc-functionality and shows superior activity compared with the monoclonal anti-GITR antibody TRX518 (CIMT 2019) - "Glucocorticoid-induced TNFR-related protein (GITR, TNFRSF18, CD357), a TNFR-SF member, is a co-stimulatory receptor that increases anti-tumor T cell activation. A comparison of HERA-GITRL with the anti-GITR antibody TRX518 showed superior agonistic activity of our HERA construct in vitro with and without cross-linking. The HERA-ligand concept has also been successfully translated to HERA-TRAIL (now in Phase I), -CD40L, -CD27L,-LIGHT and -4-1BBL."

Clinical

The novel hexavalent human GITR agonist HERA-GITRL promotes anti-tumor efficacy independent of Fc-functionality and shows superior activity compared with the monoclonal anti-GITR antibody TRX518 (AACR 2019) - "Glucocorticoid-induced TNFR-related protein (GITR, TNFRSF18, CD357), a TNFR-SF member, is a co-stimulatory receptor that increases anti-tumor T cell activation. A comparison of HERA-GITRL with the anti-GITR antibody TRX518 showed superior agonistic activity of our HERA construct in vitro with and without cross-linking. The HERA-ligand concept has also been successfully translated to HERA-TRAIL (now in Phase I), -CD40L, -CD27L,-LIGHT and -4-1BBL."

Clinical