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BI-1808 and BI-1910 - anti-TNFR2 antibody for the treatment of solid tumors and CTCL

Two different types of TNFR2 targeting antibodies are being developed by BioInvent – BI-1808 in clinical development (a ligand blocker), and BI-1910 (an agonist) in preclinical development.

BioInvent announced, in October 2020, regulatory authority approval of a clinical trial application (CTA) in Denmark for a Phase I/IIa, first-in-human study of BI-1808 for the treatment of solid tumors and CTCL. The first patient was enrolled in January 2021.

Background
BioInvent has identified tumor necrosis factor receptor 2 (TNFR2), a member of the so-called TNFR superfamily (TNFRS) as a target within the Treg program. TNFR2 is particularly upregulated on tumor-associated regulatory T cells (Tregs) and has been shown to be important for their expansion and survival. As a part of its Treg program, BioInvent identified and characterized a wide panel of TNFR2-specific antibodies, generated from its proprietary n-CoDeR® library and unique F.I.R.S.TTM discovery tool, of which BI-1808 and BI-1910 are the lead development candidates.

The Phase I stage is divided into two parts. Part A is a dose escalation study of BI-1808 to assess safety, tolerability, pharmacokinetics/pharmacodynamics, and to determine the recommended dose as a single agent for Phase II trials. Part B will explore the safety, tolerability and recommended dose of BI-1808 in combination with Keytruda®. The Phase IIa stage will consist of expansion cohorts to assess signs of efficacy of BI-1808 as single agent, and in combination with Keytruda® in lung cancer and ovarian cancer patients. Another cohort will explore the activity as single agent in CTCL. The trial will be conducted at several sites across Europe and the U.S. and is expected to enroll approximately 120 patients.

Exciting preclinical data was presented at AACR Virtual Annual Meeting II in June 2020. In vivo studies show that both ligand-blocking (BI-1808 surrogate) and agonistic (BI-1910 surrogate) antibodies regress large established tumors and synergize with anti-PD-1 therapy. Further mode-of-action dissection demonstrate that while the ligand-blocking antibody depleted intratumoral Tregs, the agonist increased intratumoral CD8+ T effector cells. Both antibodies expanded tumor-specific CD8+ T cells and induced long-lasting T cell memory.

New translational data was presented on BI-1808 at the SITC 35th Anniversary Annual Meeting. The data showed that BI-1808 had an expected pharmacokinetic profile and was well tolerated in a toxicology study in doses up to 200 mg/kg.