The tumor microenvironment (TME), in particular the presence and immune-status of myeloid derived suppressor cells (MDSC), tumor-associated macrophages (TAM) as well as dendritic cells, has been closely linked to tumor activity and responsiveness to T-cell-targeted immunotherapies.

OSE Immunotherapeutics’ R&D team has taken interest in this critical aspect of research by focusing on SIRPα, on the CD47/SIRPα pathway, a receptor strongly expressed by myeloid and suppressive macrophage cells.

BI 765063 (formerly OSE-172) is an antibody antagonist of SIRPα, a binding partner for the “Don’t eat me“ signal CD47, which is expressed by tumors to escape detection from the immune system. Blocking SIRPα enables tumor associated macrophages and dendritic cells to resume their phagocytosis activity and control / destroy tumor.

In addition, BI 765063, as a SIRPα antagonist and first-in-class myeloid checkpoint inhibitor, inhibits the creation of pro-tumorigenic suppressor cells and restores their function. Pre-clinical studies have demonstrated BI 765063’s ability to inhibit pro-tumorigenic cells while activating anti-tumorigenic ones within the TME, generating high interest for this innovative breakthrough approach.

OSE is actively working on several new approaches focused on modulating the tumor microenvironment.

ABOUT THE BI 765063 CLINICAL PROGRAM

A Phase 1 clinical trial is ongoing to evaluate BI 765063 in patients with advanced solid tumors.

The Phase 1 is a dose finding study of monoclonal antibody SIRPα antagonist, BI 765063, a myeloid checkpoint inhibitor administered as a single agent and in combination with the monoclonal antibody PD-1 antagonist ezabenlimab, a T lymphocyte checkpoint inhibitor, developed by Boehringer Ingelheim.

This trial aims to characterize safety, pharmacokinetics, pharmacodynamics and preliminary efficacy in patients with advanced solid tumors (ClinicalTrials.gov: NCT03990233).

The study is conducted by OSE as part of a collaboration and license agreement with Boehringer Ingelheim under which Boehringer Ingelheim obtained exclusive rights to BI 765063.

We recently completed the dose escalation part (Step 1) of the Phase 1 trial evaluating BI 765063 alone and in combination with BI 754091 (ezabenlimab) in advanced solid tumors.

Data presented at the 2021 ASCO meeting indicated that BI 765063 was well tolerated and showed monotherapy activity in heavily pre-treated solid tumor patients. In particular, a durable partial response was observed in an advanced hepatocellular carcinoma (HCC) patient.

Additional data from the dose escalation part of the trial of BI 765063 in combination with anti-PD-1 ezabenlimab BI 754091 were presented at the ESMO 2021 (European Society for Medical Oncology) congress. That data demonstrated a good safety profile and promising early clinical efficacy in heavily pretreated patients with solid tumors. In particular, three partial responses (PR) in patients with microsatellite stable (MSS) advanced endometrium or colorectal cancer were observed.

The trial is currently recruiting MSS advanced colorectal and advanced endometrium cancer patients in the expansion part of the Phase 1 trial (Step 2).